Back to resultsA Study to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors (STASEY)
Primary Purpose
Hemophilia A
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Emicizumab
Sponsored by
About this trial
This is an interventional treatment trial for Hemophilia A
Eligibility Criteria
Inclusion Criteria:
- As per investigator's judgement, a willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the patient-reported outcome (PRO) questionnaires and bleed diaries through the use of an electronic device or paper
- Aged 12 years or older at the time of informed consent
- Diagnosis of congenital hemophilia A with persistent inhibitors against FVIII
- Documented treatment with bypassing agents or FVIII concentrates in the last 6 months (on-demand or prophylaxis). Prophylaxis needs to be discontinued the latest by a day before starting emicizumab
- Adequate hematologic, hepatic, and renal function
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method with a failure rate of <1% per year during the treatment period and for at least five elimination half-lives (24 weeks) after the last dose of emicizumab
Exclusion Criteria:
- Inherited or acquired bleeding disorder other than hemophilia A
- Ongoing (or plan to receive during the study) immune tolerance induction (ITI) therapy (prophylaxis regimens with FVIII and/or bypassing agents must be discontinued prior to enrollment). Patients receiving ITI therapy will be eligible following the completion of a 72-hour washout period prior to the first emicizumab administration
- History of illicit drug or alcohol abuse within 12 months prior to screening, as per the investigator's judgment
- High risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), as per the investigator's judgment
- Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which antithrombotic treatment is not currently ongoing) or current signs of thromboembolic disease
- Other conditions (e.g., certain autoimmune diseases) that may increase the risk of bleeding or thrombosis
- History of clinically significant hypersensitivity reaction associated with monoclonal antibody therapies or components of the emicizumab injection
- Known human immunodeficiency virus (HIV) infection with CD4 count <200 cells/μL within 6 months prior to screening
- Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or planned use during the study, with the exception of antiretroviral therapy
- Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the patient's safe participation in and completion of the study or interpretation of the study results
- Receipt of: Emicizumab in a prior investigational study; An investigational drug to treat or reduce the risk of hemophilic bleeds within five half-lives of last drug administration; A non-hemophilia-related investigational drug within last 30 days or five half-lives, whichever is shorter; or, Any concurrent investigational drug.
- Pregnancy or lactation, or intent to become pregnant during the study
- Positive serum pregnancy test result within 7 days prior to initiation of emicizumab (females only)
Sites / Locations
- Royal Prince Alfred Hospital; Haematology
- Alfred Hospital
- Fiona Stanley Hospital
- UZ Leuven Gasthuisberg
- Centro de Hematologia E Hemoterapia Do Parana - Hemepar
- Instituto Estadual de Hema
- Hospital das Clinicas - UNICAMP
- Faculdade de Medicina de Ribeirão Preto - Universidade de Sao Paulo
- Kaye Edmonton Clinic
- CancerCare Manitoba; Neuro-Oncology
- McMaster University Health Sciences Center
- St. Michael's Hospital
- Centro de Atención e Investigación Médica CAIMED S.A.S
- Hospital Pablo Tobon Uribe
- Helsingin yliopistollinen keskussairaala, Meilahden sairaala
- Vivantes Klinikum im Friedrichshain - Landsberger Allee, Angiologie und Hämostaseologie
- Universitätsklinikum Bonn; Institut für Experimentelle Hämatologie und Transfusionsmedizin
- Hämophiliezentrum Med. Klinik III/Institut für Transfusionsmedizin; Johann Wolfgang Goethe-Univers.
- Universitätsklinikum Leipzig, Innere Medizin, Neurologie, Dermatologie; Zentrum für Hämostaseologie
- Hämophilie-Zentrum Rhein Main GmbH
- Klinikum der Universität München, Campus Innenstadt; Hämostaseologische Ambulanz/Hämophiliezentrum
- Oncomedica
- Magyar Honvédség Egészségügyi Központ; Országos Haemophilia Központ
- Országos Vérellátó Szolgálat - Győri Regionális Vérellátó Központ
- University of Pecs, I st Dept of Internal Medicine
- St. John's Medical College & Hospital; Department of Medicine
- King Edward Memorial Hospital and Seth G.S. Medical College; Department of Hematology
- Fortis Hospitals Limited
- Sahyadri Speciality Hospital; Hematology & Bone Marrow Unit
- Christian Medical College & Hospital; Department of Haematology
- Nil Ratan Sircar Medical College and Hospital; Department of Hematology
- Grant Medical Foundation, Ruby Hall Clinic
- Sheba Medical Center - National Hemophilia Center
- AOU Federico II; Medicina Clinica Chirurgia Centro Emocoaugulopatie e Emofilia
- AOU Policlinico S. Orsola Malpighi; U.O. Angiologia e Malattie della Coagulazione Marino Golinelli
- AOU di Parma; Dip Emergenza-Urgenza Centro Riferimento Regionale per l'emofilia
- Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
- IRCCS Ca' Granda Ospedale Maggiore Policlinico; Centro Emofilia e Trombosi "Angelo Bianchi e Bonomi"
- AO Città Salute e Scienza D-Osp S. G. Battista Molinette; SSCVD Malattie Tromboti e Emorragiche
- Azienda Uni Ria Policlinico P. Giaccone ; Divisione Di Ematologia E Trapianto
- AOU Careggi; SOD Malattie Emorragiche
- Azienda Ospedaliera di Padova; Centro Emofilia
- Hospital General de México
- CENTRO MEDICO NACIONAL SIGLO XXI; Banco de Sangre
- Hospital de Especialidades Centro Medico Nacional La Raza; Haematology
- Erasmus MC / location Sophia Kinderziekenhuis
- Universitair Medisch Centrum Utrecht
- Complejo Hospitalario Arnulfo Arias Madrid; Servicio de Hematología
- Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych
- Hospital Geral; Servico de Imuno-Hemoterapia
- Hospital de Santa Maria; Servico de Imuno-Hemoterapia; Servico de Imuno-Hemoterapia
- Hospital de Sao Joao; Servico de Imuno-Hemoterapia; Servico de Imuno-Hemoterapia
- Louis Turcanu Emergency Clinical Hospital for Children; First Pediatric Clinic
- Regional State Budgetary Institution of Healthcare "Regional Cinilcal Hospital"; Pulmonology
- Morozov Children's Municipal Clinical Hospital. Haematology department
- "Hematological Scientific Center
- City Outpatient Clinic #37, City Hemophilia Treatment Center
- Samara State Medical University
- King Faisal Specialist Hospital & Research Centre; Oncology
- Hospital Universitario Vall de Hebron; Unidad de Hemofília
- Hospital Universitario la Paz; Servicio de Hematologia
- Hospital Regional Universitario Carlos Haya; Servicio de Hematologia
- Hospital Universitario Virgen del Rocio; Servicio de Hematologia
- Hospital Universitario la Fe; Servicio de Hematologia
- Sahlgrenska Universitetssjukhuset; Koagulationscentrum
- Karolinska Universitetssjukhuset; Koagulationsmottagningen
- Inselspital Bern; Hämatologie und Hämatologisches Zentrallabor
- University Hospitals Birmingham NHS Foundation Trust
- The Royal London Hospital
- Royal Free Hospital
- Royal Victoria Infirmary; Non-Malignant Haematology Research
- Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Foundation Trust
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1.5 mg/kg Emicizumab QW
Arm Description
Participants will receive initial weekly doses of prophylactic emicizumab subcutaneously for 4 weeks, followed by maintenance doses consisting of half the initial dose, administered subcutaneously for the remainder of the 2-year treatment period
Outcomes
Primary Outcome Measures
Overall Summary of the Number of Participants With Adverse Events, Severity Assessed According to the World Health Organization (WHO) Toxicity Grading Scale
Investigators sought information on adverse events (AEs) at each contact with participants. The WHO toxicity grading scale was used for assessing AE severity (i.e., intensity of an AE); any AEs not specifically listed in the WHO toxicity grading scale were assessed for severity according to the following grades: Grade 1 is mild; Grade 2 is moderate, Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death. Regardless of severity, some AEs may have also met seriousness criteria. The terms "severe" and "serious" are not synonymous; severity and seriousness were independently assessed for each AE. aPCC = activated prothrombin complex concentrate
Adverse Events (AEs) Rates Per 100 Patient-Years for All-Grade AEs, Serious AEs, and Grade ≥3 AEs
Investigators sought information on adverse events (AEs) at each contact with participants. The WHO toxicity grading scale was used for assessing AE severity (i.e., intensity of an AE); any AEs not specifically listed in the WHO toxicity grading scale were assessed for severity according to the following grades: Grade 1 is mild; Grade 2 is moderate, Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death. Regardless of severity, some AEs may have also met seriousness criteria. The terms "severe" and "serious" are not synonymous; severity and seriousness were independently assessed for each AE. The AE rate per 100 patient-years was computed as follows: AE Rate = (Number of AEs observed/ Total patient-years at risk)*100. Total patient-years at risk is the sum over all patients of the time intervals (in years) between start of study therapy (study day 1) and the end of follow up.
Number of Participants by Hematology and Biochemistry Laboratory Parameter Test Results as Shifts From the WHO Toxicity Grade at Baseline to the Worst WHO Toxicity Grade Post-Baseline
The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for hematology and biochemistry parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. Abs = absolute count; SGOT/AST = aspartate aminotransferase; SGPT/ALT = alanine aminotransferase
Change From Baseline in Body Temperature at Specified Timepoints
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Change From Baseline in Systolic Blood Pressure at Specified Timepoints
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Change From Baseline in Diastolic Blood Pressure at Specified Timepoints
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Change From Baseline in Pulse Rate at Specified Timepoints
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Change From Baseline in Respiratory Rate at Specified Timepoints
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Change From Baseline in Body Weight at Specified Timepoints
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Secondary Outcome Measures
Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Joint Bleeds, Treated Target Joint Bleeds, and Treated Spontaneous Bleeds
The number of bleeds over the efficacy period was analyzed as an ABR using a negative binomial regression model. Treated bleeds: bleeds followed by a hemophilia medication reported to be a "Treatment for bleed". All bleeds: included both treated and non-treated bleeds. Treated joint bleeds: treated bleeds where bleed type was "joint bleed" accompanied by at least one of following symptoms: "increased swelling or warmth of the skin over the joint", "increasing pain" or "decreased range of motion or difficulty using the joint compared with baseline". Treated target joint bleeds: treated joint bleeds that occurred in a target joint, defined as a joint in which ≥3 treated joint bleeds occurred during the 24 weeks prior to study entry. Treated spontaneous bleeds: treated bleeds with no other known contributing factor such as trauma or procedure/surgery. For all bleed types, bleeds due to surgery/procedure were excluded. Bleeds occurring after dose up-titration have been excluded.
Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Joint Bleeds, Treated Target Joint Bleeds, and Treated Spontaneous Bleeds
The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: bleeds followed by a hemophilia medication reported to be a "Treatment for bleed". All bleeds: included both treated and non-treated bleeds. Treated joint bleeds: treated bleeds where bleed type was "joint bleed" accompanied by at least one of following symptoms: "increased swelling or warmth of the skin over the joint", "increasing pain" or "decreased range of motion or difficulty using the joint compared with baseline". Treated target joint bleeds: treated joint bleeds that occurred in a target joint, defined as a joint in which ≥3 treated joint bleeds occurred during the 24 weeks prior to study entry. Treated spontaneous bleeds: treated bleeds with no other known contributing factor such as trauma or procedure/surgery. For all types, bleeds due to surgery/procedure and bleeds occurring after dose up-titration were excluded.
Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Joint Bleeds, Treated Target Joint Bleeds, and Treated Spontaneous Bleeds
The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: bleeds followed by a hemophilia medication reported to be a "Treatment for bleed". All bleeds: included both treated and non-treated bleeds. Treated joint bleeds: treated bleeds where bleed type was "joint bleed" accompanied by at least one of following symptoms: "increased swelling or warmth of the skin over the joint", "increasing pain" or "decreased range of motion or difficulty using the joint compared with baseline". Treated target joint bleeds: treated joint bleeds that occurred in a target joint, defined as a joint in which ≥3 treated joint bleeds occurred during the 24 weeks prior to study entry. Treated spontaneous bleeds: treated bleeds with no other known contributing factor such as trauma or procedure/surgery. For all types, bleeds due to surgery/procedure and bleeds occurring after dose up-titration were excluded.
Percentage of Participants by the Categorized Number of Bleeds for Treated Bleeds
Treated bleeds: bleeds followed by a hemophilia medication reported to be a "Treatment for bleed". Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Percentage of Participants by the Categorized Number of Bleeds for All Bleeds
All bleeds: included both treated and non-treated bleeds. Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Percentage of Participants by the Categorized Number of Bleeds for Treated Spontaneous Bleeds
Treated spontaneous bleeds: treated bleeds with no other known contributing factor such as trauma or procedure/surgery. Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Percentage of Participants by the Categorized Calculated Annualized Bleed Rates (ABR) for Treated Bleeds
The number of bleeds over the efficacy period was calculated as an ABR for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: bleeds followed by a hemophilia medication reported to be a "Treatment for bleed". Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Percentage of Participants by the Categorized Calculated Annualized Bleed Rates (ABR) for All Bleeds
The number of bleeds over the efficacy period was calculated as an ABR for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds: included both treated and non-treated bleeds. Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Percentage of Participants by the Categorized Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds
The number of bleeds over the efficacy period was calculated as an ABR for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds: treated bleeds with no other known contributing factor such as trauma or procedure/surgery. Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Total Score at Specified Timepoints, Adult Participants
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. The Total Score is based on the scores for each domain and ranges from 0 to 100, with lower scores reflective of better quality of life.
Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Total Score at Specified Timepoints
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. The Total Score is based on the scores for each domain and ranges from 0 to 100, with lower scores reflective of better quality of life. An improvement larger than the responder threshold was defined as a decrease from baseline of at least 7 points in the Haem-A-QoL Total score.
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Physical Health Domain Score at Specified Timepoints, Adult Participants
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Physical Health Domain Score at Specified Timepoints
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life. An improvement larger than the responder threshold was defined as a decrease from baseline of at least 10 points in the Haem-A-QoL Physical Health domain score.
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Treatment Domain Score at Specified Timepoints, Adult Participants
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Work and School Domain Score at Specified Timepoints, Adult Participants
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Dealing With Hemophilia Domain Score at Specified Timepoints, Adult Participants
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Feelings Domain Score at Specified Timepoints, Adult Participants
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Family Planning Domain Score at Specified Timepoints, Adult Participants
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Future Domain Score at Specified Timepoints, Adult Participants
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Partnership and Sexuality Domain Score at Specified Timepoints, Adult Participants
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Sports and Leisure Domain Score at Specified Timepoints, Adult Participants
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire View of Yourself Domain Score at Specified Timepoints, Adult Participants
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score at Specified Timepoints, Adolescent Participants
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. The Total Score is derived from the scores for all domains and scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score at Specified Timepoints
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. The Total Score is derived from the scores for all domains and scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life. An improvement larger than the responder threshold was defined as a decrease of at least 5 points in the Haemo-QoL-SF Total score.
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Physical Health Domain Score at Specified Timepoints, Adolescent Participants
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Physical Health Domain Score at Specified Timepoints
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life. An improvement larger than the responder threshold was defined as a decrease of at least 10 points in the Haemo-QoL-SF Physical Health domain score.
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Treatment Domain Score at Specified Timepoints, Adolescent Participants
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Sports and School Domain Score at Specified Timepoints, Adolescent Participants
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Dealing With Hemophilia Domain Score at Specified Timepoints, Adolescent Participants
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Feelings Domain Score at Specified Timepoints, Adolescent Participants
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Family Domain Score at Specified Timepoints, Adolescent Participants
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Friends Domain Score at Specified Timepoints, Adolescent Participants
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Other People Domain Score at Specified Timepoints, Adolescent Participants
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire View of Yourself Domain Score at Specified Timepoints, Adolescent Participants
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Change From Baseline in the EuroQoL Five-Dimension-Five Levels Questionnaire (EQ-5D-5L) Index Utility Score at Specified Timepoints
The EQ-5D-5L is a generic, self-reported, preference-based health utility measure that consists of six questions and is used to assess health status and inform pharmacoeconomic evaluations. The index utility score is based on the participant's assessment of their health on five scales: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It ranges from -0.224 to 1, with 0 corresponding to death and 1 corresponding to full health; negative values correspond to health states worse than death. Higher scores indicate better quality of life.
Change From Baseline in the EuroQoL Five-Dimension-Five Levels Questionnaire (EQ-5D-5L) Quality-of-Life Visual Analogue Scale (VAS) Score at Specified Timepoints
The EQ-5D-5L is a generic, self-reported, preference-based health utility measure that consists of six questions and is used to assess health status and inform pharmacoeconomic evaluations. The visual analogue scale (VAS) ranges from 0 to 100 points, on which the participant self-assesses their current health status; 0 being the worst health you can imagine and 100 being the best health you can imagine. Higher scores are reflective of better health.
Percentage of Participants Who Preferred the New Emicizumab Treatment or the Old Hemophilia Treatment, or Without Treatment Preference, as Assessed by the EmiPref Questionnaire
The EmiPref questionnaire asked participants to specify the treatment they would prefer to continue to receive after receiving treatment with their previous episodic or prophylactic regimen and subcutaneous (SC) emicizumab, or if they had no preference. The 95% confidence intervals were calculated for one sample binomial using the Pearson-Clopper method.
Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) Against Emicizumab at Anytime Post-Baseline
'Total ADA Negative' is the sum of all subjects who tested negative for ADA in the 2 following categories: 'ADA Negative', those who are pre-dose ADA negative or are missing pre-dose ADA data and who have all negative post-dose ADA results; and 'ADA Negative (Treatment Unaffected)', a subset who are pre-dose ADA positive but do not have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample.
Mean Trough Plasma Concentrations of Emicizumab at Specified Timepoints
The trough concentration is a measure of the plasma concentration of a study drug at the end of of the dosage interval.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03191799
Brief Title
A Study to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors
Acronym
STASEY
Official Title
A Single-Arm, Multicenter Phase IIIB Clinical Trial to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors
Study Type
Interventional
2. Study Status
Record Verification Date
May 2021
Overall Recruitment Status
Completed
Study Start Date
September 5, 2017 (Actual)
Primary Completion Date
November 19, 2020 (Actual)
Study Completion Date
November 19, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a phase IIIb, single arm, open-label, multi-center study to evaluate the safety and tolerability of emicizumab in participants with congenital hemophilia A who have documented inhibitors against Factor VIII (FVIII) at enrollment. Approximately 200 participants, aged 12 or older, will be enrolled in this study and are expected to be enrolled at approximately 85 sites globally. Participants will receive an initial weekly dose of prophylactic emicizumab subcutaneously for 4 weeks, followed by a weekly maintenance dose subcutaneously for the remainder of the 2-year treatment period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemophilia A
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
195 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1.5 mg/kg Emicizumab QW
Arm Type
Experimental
Arm Description
Participants will receive initial weekly doses of prophylactic emicizumab subcutaneously for 4 weeks, followed by maintenance doses consisting of half the initial dose, administered subcutaneously for the remainder of the 2-year treatment period
Intervention Type
Drug
Intervention Name(s)
Emicizumab
Other Intervention Name(s)
Hemlibra, RO5534262, ACE910
Intervention Description
Initial dosing will be 3 mg/kg/week subcutaneously for 4 weeks; Maintenance dosing will follow at 1.5 mg/kg/week subcutaneously for the remainder of the 2-year treatment period
Primary Outcome Measure Information:
Title
Overall Summary of the Number of Participants With Adverse Events, Severity Assessed According to the World Health Organization (WHO) Toxicity Grading Scale
Description
Investigators sought information on adverse events (AEs) at each contact with participants. The WHO toxicity grading scale was used for assessing AE severity (i.e., intensity of an AE); any AEs not specifically listed in the WHO toxicity grading scale were assessed for severity according to the following grades: Grade 1 is mild; Grade 2 is moderate, Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death. Regardless of severity, some AEs may have also met seriousness criteria. The terms "severe" and "serious" are not synonymous; severity and seriousness were independently assessed for each AE. aPCC = activated prothrombin complex concentrate
Time Frame
From Baseline until study completion (up to 2 years)
Title
Adverse Events (AEs) Rates Per 100 Patient-Years for All-Grade AEs, Serious AEs, and Grade ≥3 AEs
Description
Investigators sought information on adverse events (AEs) at each contact with participants. The WHO toxicity grading scale was used for assessing AE severity (i.e., intensity of an AE); any AEs not specifically listed in the WHO toxicity grading scale were assessed for severity according to the following grades: Grade 1 is mild; Grade 2 is moderate, Grade 3 is severe; Grade 4 is life-threatening; and Grade 5 is death. Regardless of severity, some AEs may have also met seriousness criteria. The terms "severe" and "serious" are not synonymous; severity and seriousness were independently assessed for each AE. The AE rate per 100 patient-years was computed as follows: AE Rate = (Number of AEs observed/ Total patient-years at risk)*100. Total patient-years at risk is the sum over all patients of the time intervals (in years) between start of study therapy (study day 1) and the end of follow up.
Time Frame
From Baseline until study completion (up to 2 years)
Title
Number of Participants by Hematology and Biochemistry Laboratory Parameter Test Results as Shifts From the WHO Toxicity Grade at Baseline to the Worst WHO Toxicity Grade Post-Baseline
Description
The World Health Organization (WHO) toxicity grading scale was used for determining the severity of laboratory abnormalities (i.e., test results outside of the reference range) for hematology and biochemistry parameters; Grade 0 is normal and Grades 1 to 4 represent worsening levels of the parameter outside of the normal range in the specified direction of the abnormality (high and low are above and below the range, respectively). Not every laboratory abnormality qualified as an adverse event (AE). A laboratory test result was reported as an AE if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; or was clinically significant in the investigator's judgment. Baseline was defined as the last available assessment prior to first receipt of study drug. Abs = absolute count; SGOT/AST = aspartate aminotransferase; SGPT/ALT = alanine aminotransferase
Time Frame
Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
Title
Change From Baseline in Body Temperature at Specified Timepoints
Description
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Time Frame
Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
Title
Change From Baseline in Systolic Blood Pressure at Specified Timepoints
Description
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Time Frame
Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
Title
Change From Baseline in Diastolic Blood Pressure at Specified Timepoints
Description
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Time Frame
Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
Title
Change From Baseline in Pulse Rate at Specified Timepoints
Description
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Time Frame
Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
Title
Change From Baseline in Respiratory Rate at Specified Timepoints
Description
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Time Frame
Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
Title
Change From Baseline in Body Weight at Specified Timepoints
Description
Vital signs that were measured included body temperature, pulse and respiratory rates, systolic and diastolic blood pressure, and weight. On treatment days, measurement occurred prior to emicizumab administration.
Time Frame
Baseline, Weeks 2, 3, and 5; Months 3, 6, 9, 12, and 18; and at Early Termination/Study Completion (up to 24 months)
Secondary Outcome Measure Information:
Title
Model-Based Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Joint Bleeds, Treated Target Joint Bleeds, and Treated Spontaneous Bleeds
Description
The number of bleeds over the efficacy period was analyzed as an ABR using a negative binomial regression model. Treated bleeds: bleeds followed by a hemophilia medication reported to be a "Treatment for bleed". All bleeds: included both treated and non-treated bleeds. Treated joint bleeds: treated bleeds where bleed type was "joint bleed" accompanied by at least one of following symptoms: "increased swelling or warmth of the skin over the joint", "increasing pain" or "decreased range of motion or difficulty using the joint compared with baseline". Treated target joint bleeds: treated joint bleeds that occurred in a target joint, defined as a joint in which ≥3 treated joint bleeds occurred during the 24 weeks prior to study entry. Treated spontaneous bleeds: treated bleeds with no other known contributing factor such as trauma or procedure/surgery. For all bleed types, bleeds due to surgery/procedure were excluded. Bleeds occurring after dose up-titration have been excluded.
Time Frame
From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
Title
Mean Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Joint Bleeds, Treated Target Joint Bleeds, and Treated Spontaneous Bleeds
Description
The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: bleeds followed by a hemophilia medication reported to be a "Treatment for bleed". All bleeds: included both treated and non-treated bleeds. Treated joint bleeds: treated bleeds where bleed type was "joint bleed" accompanied by at least one of following symptoms: "increased swelling or warmth of the skin over the joint", "increasing pain" or "decreased range of motion or difficulty using the joint compared with baseline". Treated target joint bleeds: treated joint bleeds that occurred in a target joint, defined as a joint in which ≥3 treated joint bleeds occurred during the 24 weeks prior to study entry. Treated spontaneous bleeds: treated bleeds with no other known contributing factor such as trauma or procedure/surgery. For all types, bleeds due to surgery/procedure and bleeds occurring after dose up-titration were excluded.
Time Frame
From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
Title
Median Calculated Annualized Bleed Rates (ABR) for Treated Bleeds, All Bleeds, Treated Joint Bleeds, Treated Target Joint Bleeds, and Treated Spontaneous Bleeds
Description
The number of bleeds over the efficacy period was calculated as: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: bleeds followed by a hemophilia medication reported to be a "Treatment for bleed". All bleeds: included both treated and non-treated bleeds. Treated joint bleeds: treated bleeds where bleed type was "joint bleed" accompanied by at least one of following symptoms: "increased swelling or warmth of the skin over the joint", "increasing pain" or "decreased range of motion or difficulty using the joint compared with baseline". Treated target joint bleeds: treated joint bleeds that occurred in a target joint, defined as a joint in which ≥3 treated joint bleeds occurred during the 24 weeks prior to study entry. Treated spontaneous bleeds: treated bleeds with no other known contributing factor such as trauma or procedure/surgery. For all types, bleeds due to surgery/procedure and bleeds occurring after dose up-titration were excluded.
Time Frame
From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
Title
Percentage of Participants by the Categorized Number of Bleeds for Treated Bleeds
Description
Treated bleeds: bleeds followed by a hemophilia medication reported to be a "Treatment for bleed". Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Time Frame
From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
Title
Percentage of Participants by the Categorized Number of Bleeds for All Bleeds
Description
All bleeds: included both treated and non-treated bleeds. Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Time Frame
From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
Title
Percentage of Participants by the Categorized Number of Bleeds for Treated Spontaneous Bleeds
Description
Treated spontaneous bleeds: treated bleeds with no other known contributing factor such as trauma or procedure/surgery. Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Time Frame
From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
Title
Percentage of Participants by the Categorized Calculated Annualized Bleed Rates (ABR) for Treated Bleeds
Description
The number of bleeds over the efficacy period was calculated as an ABR for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated bleeds: bleeds followed by a hemophilia medication reported to be a "Treatment for bleed". Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Time Frame
From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
Title
Percentage of Participants by the Categorized Calculated Annualized Bleed Rates (ABR) for All Bleeds
Description
The number of bleeds over the efficacy period was calculated as an ABR for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. All bleeds: included both treated and non-treated bleeds. Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Time Frame
From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
Title
Percentage of Participants by the Categorized Calculated Annualized Bleed Rates (ABR) for Treated Spontaneous Bleeds
Description
The number of bleeds over the efficacy period was calculated as an ABR for each participant using the following formula: ABR = (number of bleeds/number of days during the efficacy period) x 365.25. Treated spontaneous bleeds: treated bleeds with no other known contributing factor such as trauma or procedure/surgery. Bleeds due to surgery/procedure were excluded. The 72-hour rule was implemented: two bleeds of the same type and at the same anatomical location are counted as one bleed if the second bleed occurs within 72 hours from the last treatment for the first bleed. Included data before up-titration only, for participants whose dose was up-titrated.
Time Frame
From first dose of emicizumab until dose up-titration or withdrawal from treatment (median [min-max] efficacy period: 103.14 [1.1-108.3] weeks)
Title
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Total Score at Specified Timepoints, Adult Participants
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. The Total Score is based on the scores for each domain and ranges from 0 to 100, with lower scores reflective of better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Total Score at Specified Timepoints
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. The Total Score is based on the scores for each domain and ranges from 0 to 100, with lower scores reflective of better quality of life. An improvement larger than the responder threshold was defined as a decrease from baseline of at least 7 points in the Haem-A-QoL Total score.
Time Frame
At 3, 6, 12, and 18 months
Title
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Physical Health Domain Score at Specified Timepoints, Adult Participants
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Physical Health Domain Score at Specified Timepoints
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life. An improvement larger than the responder threshold was defined as a decrease from baseline of at least 10 points in the Haem-A-QoL Physical Health domain score.
Time Frame
At 3, 6, 12, and 18 months
Title
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Treatment Domain Score at Specified Timepoints, Adult Participants
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Work and School Domain Score at Specified Timepoints, Adult Participants
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Dealing With Hemophilia Domain Score at Specified Timepoints, Adult Participants
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Feelings Domain Score at Specified Timepoints, Adult Participants
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Family Planning Domain Score at Specified Timepoints, Adult Participants
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Future Domain Score at Specified Timepoints, Adult Participants
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Partnership and Sexuality Domain Score at Specified Timepoints, Adult Participants
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire Sports and Leisure Domain Score at Specified Timepoints, Adult Participants
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Adult Quality of Life (Haem-A-QoL) Questionnaire View of Yourself Domain Score at Specified Timepoints, Adult Participants
Description
The Haem-A-QoL questionnaire was designed for adult participants (greater than or equal to 18 years old) with hemophilia. It consists of 46 items comprising 10 domains: physical health, treatment, work and school, dealing with hemophilia, feelings, familly planning, future, partnerships and sexuality, sports and leisure, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always; although, for some items there is also a 'not applicable' option. Scale scores for each domain range from 0 to 100, with lower scores reflective of better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score at Specified Timepoints, Adolescent Participants
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. The Total Score is derived from the scores for all domains and scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Total Score at Specified Timepoints
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. The Total Score is derived from the scores for all domains and scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life. An improvement larger than the responder threshold was defined as a decrease of at least 5 points in the Haemo-QoL-SF Total score.
Time Frame
At 3, 6, 12, and 18 months
Title
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Physical Health Domain Score at Specified Timepoints, Adolescent Participants
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Percentage of Participants With an Improvement From Baseline Greater Than the Responder Threshold for the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Physical Health Domain Score at Specified Timepoints
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life. An improvement larger than the responder threshold was defined as a decrease of at least 10 points in the Haemo-QoL-SF Physical Health domain score.
Time Frame
At 3, 6, 12, and 18 months
Title
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Treatment Domain Score at Specified Timepoints, Adolescent Participants
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Sports and School Domain Score at Specified Timepoints, Adolescent Participants
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Dealing With Hemophilia Domain Score at Specified Timepoints, Adolescent Participants
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Feelings Domain Score at Specified Timepoints, Adolescent Participants
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Family Domain Score at Specified Timepoints, Adolescent Participants
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Friends Domain Score at Specified Timepoints, Adolescent Participants
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire Other People Domain Score at Specified Timepoints, Adolescent Participants
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the Hemophilia Quality of Life Short Form (Haemo-QoL-SF) Questionnaire View of Yourself Domain Score at Specified Timepoints, Adolescent Participants
Description
The Haemo-QoL-SF was designed as a series of age-related questionnaires to measure health-related quality of life in children and adolescents (12-17 year olds) with hemophilia. This version contains 35 items and covers nine domains considered relevant for children's health-related quality of life: physical health, treatment, sports and school, dealing with hemophilia, feelings, family, friends, other people, and view of yourself. Items are rated by participants with one of five response options: never, seldom, sometimes, often, and always. Scale scores range from 0 to 100, with a lower score reflective of better health-related quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the EuroQoL Five-Dimension-Five Levels Questionnaire (EQ-5D-5L) Index Utility Score at Specified Timepoints
Description
The EQ-5D-5L is a generic, self-reported, preference-based health utility measure that consists of six questions and is used to assess health status and inform pharmacoeconomic evaluations. The index utility score is based on the participant's assessment of their health on five scales: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. It ranges from -0.224 to 1, with 0 corresponding to death and 1 corresponding to full health; negative values correspond to health states worse than death. Higher scores indicate better quality of life.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Change From Baseline in the EuroQoL Five-Dimension-Five Levels Questionnaire (EQ-5D-5L) Quality-of-Life Visual Analogue Scale (VAS) Score at Specified Timepoints
Description
The EQ-5D-5L is a generic, self-reported, preference-based health utility measure that consists of six questions and is used to assess health status and inform pharmacoeconomic evaluations. The visual analogue scale (VAS) ranges from 0 to 100 points, on which the participant self-assesses their current health status; 0 being the worst health you can imagine and 100 being the best health you can imagine. Higher scores are reflective of better health.
Time Frame
Baseline (Week 1), 3, 6, 12, and 18 months, and at Early Termination or Study Completion (up to 24 months)
Title
Percentage of Participants Who Preferred the New Emicizumab Treatment or the Old Hemophilia Treatment, or Without Treatment Preference, as Assessed by the EmiPref Questionnaire
Description
The EmiPref questionnaire asked participants to specify the treatment they would prefer to continue to receive after receiving treatment with their previous episodic or prophylactic regimen and subcutaneous (SC) emicizumab, or if they had no preference. The 95% confidence intervals were calculated for one sample binomial using the Pearson-Clopper method.
Time Frame
Month 3
Title
Number and Percentage of Participants With Anti-Drug Antibodies (ADAs) Against Emicizumab at Anytime Post-Baseline
Description
'Total ADA Negative' is the sum of all subjects who tested negative for ADA in the 2 following categories: 'ADA Negative', those who are pre-dose ADA negative or are missing pre-dose ADA data and who have all negative post-dose ADA results; and 'ADA Negative (Treatment Unaffected)', a subset who are pre-dose ADA positive but do not have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement. 'Total ADA Positive' is the sum of all subjects who tested positive for ADA in the 2 following categories: 'ADA Positive (Treatment Boosted)', those who are pre-dose ADA positive and have a ≥4-fold increase in post-dose ADA levels compared to baseline measurement; and 'ADA Positive (Treatment Induced)', those who are pre-dose ADA negative or missing data and who have at least one post-dose ADA positive sample.
Time Frame
Baseline (Week 1), Week 5, and at 3, 6, 9, 12, and 18 months, and at early termination/study completion (up to 24 months)
Title
Mean Trough Plasma Concentrations of Emicizumab at Specified Timepoints
Description
The trough concentration is a measure of the plasma concentration of a study drug at the end of of the dosage interval.
Time Frame
Pre-dose at Weeks 2, 3, and 5, Months 3, 6, 12, and 18, and at treatment discontinuation (up to 2 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
As per investigator's judgement, a willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including the patient-reported outcome (PRO) questionnaires and bleed diaries through the use of an electronic device or paper
Aged 12 years or older at the time of informed consent
Diagnosis of congenital hemophilia A with persistent inhibitors against FVIII
Documented treatment with bypassing agents or FVIII concentrates in the last 6 months (on-demand or prophylaxis). Prophylaxis needs to be discontinued the latest by a day before starting emicizumab
Adequate hematologic, hepatic, and renal function
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a highly effective contraceptive method with a failure rate of <1% per year during the treatment period and for at least five elimination half-lives (24 weeks) after the last dose of emicizumab
Exclusion Criteria:
Inherited or acquired bleeding disorder other than hemophilia A
Ongoing (or plan to receive during the study) immune tolerance induction (ITI) therapy (prophylaxis regimens with FVIII and/or bypassing agents must be discontinued prior to enrollment). Patients receiving ITI therapy will be eligible following the completion of a 72-hour washout period prior to the first emicizumab administration
History of illicit drug or alcohol abuse within 12 months prior to screening, as per the investigator's judgment
High risk for thrombotic microangiopathy (TMA) (e.g., have a previous medical or family history of TMA), as per the investigator's judgment
Previous (in the past 12 months) or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which antithrombotic treatment is not currently ongoing) or current signs of thromboembolic disease
Other conditions (e.g., certain autoimmune diseases) that may increase the risk of bleeding or thrombosis
History of clinically significant hypersensitivity reaction associated with monoclonal antibody therapies or components of the emicizumab injection
Known human immunodeficiency virus (HIV) infection with CD4 count <200 cells/μL within 6 months prior to screening
Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or planned use during the study, with the exception of antiretroviral therapy
Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the patient's safe participation in and completion of the study or interpretation of the study results
Receipt of: Emicizumab in a prior investigational study; An investigational drug to treat or reduce the risk of hemophilic bleeds within five half-lives of last drug administration; A non-hemophilia-related investigational drug within last 30 days or five half-lives, whichever is shorter; or, Any concurrent investigational drug.
Pregnancy or lactation, or intent to become pregnant during the study
Positive serum pregnancy test result within 7 days prior to initiation of emicizumab (females only)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Royal Prince Alfred Hospital; Haematology
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Facility Name
Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Fiona Stanley Hospital
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6150
Country
Australia
Facility Name
UZ Leuven Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Centro de Hematologia E Hemoterapia Do Parana - Hemepar
City
Curitiba
State/Province
PR
ZIP/Postal Code
80045-145
Country
Brazil
Facility Name
Instituto Estadual de Hema
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
20211-030
Country
Brazil
Facility Name
Hospital das Clinicas - UNICAMP
City
Campinas
State/Province
SP
ZIP/Postal Code
13083-888
Country
Brazil
Facility Name
Faculdade de Medicina de Ribeirão Preto - Universidade de Sao Paulo
City
Ribeirao Preto
State/Province
SP
ZIP/Postal Code
14051-140
Country
Brazil
Facility Name
Kaye Edmonton Clinic
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2V2
Country
Canada
Facility Name
CancerCare Manitoba; Neuro-Oncology
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R2H 2A6
Country
Canada
Facility Name
McMaster University Health Sciences Center
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
St. Michael's Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1W8
Country
Canada
Facility Name
Centro de Atención e Investigación Médica CAIMED S.A.S
City
Localidad Puente Aranda
ZIP/Postal Code
111611
Country
Colombia
Facility Name
Hospital Pablo Tobon Uribe
City
Medellin
ZIP/Postal Code
050034
Country
Colombia
Facility Name
Helsingin yliopistollinen keskussairaala, Meilahden sairaala
City
Helsinki
ZIP/Postal Code
00290
Country
Finland
Facility Name
Vivantes Klinikum im Friedrichshain - Landsberger Allee, Angiologie und Hämostaseologie
City
Berlin
ZIP/Postal Code
10249
Country
Germany
Facility Name
Universitätsklinikum Bonn; Institut für Experimentelle Hämatologie und Transfusionsmedizin
City
Bonn
ZIP/Postal Code
53127
Country
Germany
Facility Name
Hämophiliezentrum Med. Klinik III/Institut für Transfusionsmedizin; Johann Wolfgang Goethe-Univers.
City
Frankfurt/M.
ZIP/Postal Code
60590
Country
Germany
Facility Name
Universitätsklinikum Leipzig, Innere Medizin, Neurologie, Dermatologie; Zentrum für Hämostaseologie
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Hämophilie-Zentrum Rhein Main GmbH
City
Mörfelden-Walldorf
ZIP/Postal Code
64546
Country
Germany
Facility Name
Klinikum der Universität München, Campus Innenstadt; Hämostaseologische Ambulanz/Hämophiliezentrum
City
München
ZIP/Postal Code
80336
Country
Germany
Facility Name
Oncomedica
City
Guatemala
ZIP/Postal Code
01010
Country
Guatemala
Facility Name
Magyar Honvédség Egészségügyi Központ; Országos Haemophilia Központ
City
Budapest
ZIP/Postal Code
1134
Country
Hungary
Facility Name
Országos Vérellátó Szolgálat - Győri Regionális Vérellátó Központ
City
Győr
ZIP/Postal Code
9023
Country
Hungary
Facility Name
University of Pecs, I st Dept of Internal Medicine
City
Pecs
ZIP/Postal Code
7624
Country
Hungary
Facility Name
St. John's Medical College & Hospital; Department of Medicine
City
Bengaluru
State/Province
Karnataka
ZIP/Postal Code
560034
Country
India
Facility Name
King Edward Memorial Hospital and Seth G.S. Medical College; Department of Hematology
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400012
Country
India
Facility Name
Fortis Hospitals Limited
City
Mumbai
State/Province
Maharashtra
ZIP/Postal Code
400078
Country
India
Facility Name
Sahyadri Speciality Hospital; Hematology & Bone Marrow Unit
City
Pune
State/Province
Maharashtra
ZIP/Postal Code
411004
Country
India
Facility Name
Christian Medical College & Hospital; Department of Haematology
City
Vellore
State/Province
Maharashtra
ZIP/Postal Code
632004
Country
India
Facility Name
Nil Ratan Sircar Medical College and Hospital; Department of Hematology
City
Kolkata
State/Province
WEST Bengal
ZIP/Postal Code
700014
Country
India
Facility Name
Grant Medical Foundation, Ruby Hall Clinic
City
Pune
ZIP/Postal Code
411001
Country
India
Facility Name
Sheba Medical Center - National Hemophilia Center
City
Tel Hashomer
ZIP/Postal Code
5262100
Country
Israel
Facility Name
AOU Federico II; Medicina Clinica Chirurgia Centro Emocoaugulopatie e Emofilia
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
AOU Policlinico S. Orsola Malpighi; U.O. Angiologia e Malattie della Coagulazione Marino Golinelli
City
Bologna
State/Province
Emilia-Romagna
ZIP/Postal Code
40138
Country
Italy
Facility Name
AOU di Parma; Dip Emergenza-Urgenza Centro Riferimento Regionale per l'emofilia
City
Parma
State/Province
Emilia-Romagna
ZIP/Postal Code
43126
Country
Italy
Facility Name
Universita' Degli Studi La Sapienza-Ist.Di Ematologia; Dip Biot Cel e Ematol
City
Roma
State/Province
Lazio
ZIP/Postal Code
00161
Country
Italy
Facility Name
IRCCS Ca' Granda Ospedale Maggiore Policlinico; Centro Emofilia e Trombosi "Angelo Bianchi e Bonomi"
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20122
Country
Italy
Facility Name
AO Città Salute e Scienza D-Osp S. G. Battista Molinette; SSCVD Malattie Tromboti e Emorragiche
City
Torino
State/Province
Piemonte
ZIP/Postal Code
10126
Country
Italy
Facility Name
Azienda Uni Ria Policlinico P. Giaccone ; Divisione Di Ematologia E Trapianto
City
Palermo
State/Province
Sicilia
ZIP/Postal Code
90127
Country
Italy
Facility Name
AOU Careggi; SOD Malattie Emorragiche
City
Firenze
State/Province
Toscana
ZIP/Postal Code
50134
Country
Italy
Facility Name
Azienda Ospedaliera di Padova; Centro Emofilia
City
Padova
State/Province
Veneto
ZIP/Postal Code
35128
Country
Italy
Facility Name
Hospital General de México
City
Distrito Federal
State/Province
Mexico CITY (federal District)
ZIP/Postal Code
06726
Country
Mexico
Facility Name
CENTRO MEDICO NACIONAL SIGLO XXI; Banco de Sangre
City
Mexico City
State/Province
Mexico CITY (federal District)
ZIP/Postal Code
06720
Country
Mexico
Facility Name
Hospital de Especialidades Centro Medico Nacional La Raza; Haematology
City
Mexico City
ZIP/Postal Code
02990
Country
Mexico
Facility Name
Erasmus MC / location Sophia Kinderziekenhuis
City
Rotterdam
ZIP/Postal Code
3015 GJ
Country
Netherlands
Facility Name
Universitair Medisch Centrum Utrecht
City
Utrecht
ZIP/Postal Code
3584 CX
Country
Netherlands
Facility Name
Complejo Hospitalario Arnulfo Arias Madrid; Servicio de Hematología
City
Panama City
ZIP/Postal Code
0824
Country
Panama
Facility Name
Instytut Hematologii i Transfuzjologii; Klinika Zaburzeń Hemostazy i Chorób Wewnętrznych
City
Warsaw
ZIP/Postal Code
02-776
Country
Poland
Facility Name
Hospital Geral; Servico de Imuno-Hemoterapia
City
Coimbra
ZIP/Postal Code
3041-853
Country
Portugal
Facility Name
Hospital de Santa Maria; Servico de Imuno-Hemoterapia; Servico de Imuno-Hemoterapia
City
Lisboa
ZIP/Postal Code
1649-035
Country
Portugal
Facility Name
Hospital de Sao Joao; Servico de Imuno-Hemoterapia; Servico de Imuno-Hemoterapia
City
Porto
ZIP/Postal Code
4200-319
Country
Portugal
Facility Name
Louis Turcanu Emergency Clinical Hospital for Children; First Pediatric Clinic
City
Timisoara
ZIP/Postal Code
300011
Country
Romania
Facility Name
Regional State Budgetary Institution of Healthcare "Regional Cinilcal Hospital"; Pulmonology
City
Barnaul
State/Province
Altaj
ZIP/Postal Code
656024
Country
Russian Federation
Facility Name
Morozov Children's Municipal Clinical Hospital. Haematology department
City
Moscow
ZIP/Postal Code
119049
Country
Russian Federation
Facility Name
"Hematological Scientific Center
City
Moscow
ZIP/Postal Code
125167
Country
Russian Federation
Facility Name
City Outpatient Clinic #37, City Hemophilia Treatment Center
City
Saint Petersburg
ZIP/Postal Code
191186
Country
Russian Federation
Facility Name
Samara State Medical University
City
Samara
ZIP/Postal Code
443099
Country
Russian Federation
Facility Name
King Faisal Specialist Hospital & Research Centre; Oncology
City
Riyadh
ZIP/Postal Code
11211
Country
Saudi Arabia
Facility Name
Hospital Universitario Vall de Hebron; Unidad de Hemofília
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Hospital Universitario la Paz; Servicio de Hematologia
City
Madrid
ZIP/Postal Code
28046
Country
Spain
Facility Name
Hospital Regional Universitario Carlos Haya; Servicio de Hematologia
City
Malaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Hospital Universitario Virgen del Rocio; Servicio de Hematologia
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Facility Name
Hospital Universitario la Fe; Servicio de Hematologia
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Sahlgrenska Universitetssjukhuset; Koagulationscentrum
City
Göteborg
ZIP/Postal Code
413 45
Country
Sweden
Facility Name
Karolinska Universitetssjukhuset; Koagulationsmottagningen
City
Solna
ZIP/Postal Code
171 64
Country
Sweden
Facility Name
Inselspital Bern; Hämatologie und Hämatologisches Zentrallabor
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Facility Name
University Hospitals Birmingham NHS Foundation Trust
City
Birmingham
ZIP/Postal Code
B15 2TH
Country
United Kingdom
Facility Name
The Royal London Hospital
City
London
ZIP/Postal Code
E1 2ES
Country
United Kingdom
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2QS
Country
United Kingdom
Facility Name
Royal Victoria Infirmary; Non-Malignant Haematology Research
City
Newcastle upon Tyne
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
Royal Hallamshire Hospital Sheffield Teaching Hospitals NHS Foundation Trust
City
Sheffield
ZIP/Postal Code
S10 2JF
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
A Study to Evaluate the Safety and Tolerability of Prophylactic Emicizumab in Hemophilia A Patients With Inhibitors
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