Back to resultsA Study of TAK-755 in Participants With Congenital Thrombotic Thrombocytopenic Purpura
Primary Purpose
Thrombotic Thrombocytopenic Purpura (TTP)
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
TAK-755
Sponsored by
About this trial
This is an interventional treatment trial for Thrombotic Thrombocytopenic Purpura (TTP) focused on measuring Congenital Thrombotic Thrombocytopenic Purpura (TTP)
Eligibility Criteria
Inclusion Criteria:
Participants who have completed TAK-755 Phase 3 pivotal Study 281102 (NCT03393975) in the prophylactic cohort and who meet all of the following criteria are eligible for this study:
- Participants or legally authorized representative has provided signed informed consent >=18 years of age and/or assent form <18 years of age.
- Participant 0 to 70 years of age at the time of screening of the 281102 (NCT03393975) study.
- Participant has been diagnosed with severe congenital ADAMTS-13 deficiency.
- Participant does not display any severe thrombotic thrombocytopenic purpura (TTP) signs (platelet count <100,000/ microliter (mcL) and elevation of lactate dehydrogenase (LDH) greater than (>) 2 × ULN at screening (prophylactic cohort only).
- Participants >=16 years of age must have a Karnofsky score >= 70% and participants <16 years of age must have a Lansky score >=80%.
- If female of childbearing potential, participant presents with a negative serum or urine pregnancy test confirmed not more than 7 days before the first IP administration and agrees to employ adequate birth control measures for the duration of the study and to undergo quarterly pregnancy testing.
- Sexually active males must use an accepted and effective method of contraception during the treatment and until a minimum of 16 days after the last dose administered.
- Participant is willing and able to comply with the requirements of the protocol.
All naïve participants and non-naïve on-demand cohort participants:
Naïve participants can only be enrolled in this continuation after enrollment of the adult participants in the prophylactic arm of TAK-755 Phase 3 pivotal study 281102 (NCT03393975) has been completed. Naïve pediatric participants can be enrolled after enrollment of the respective age cohort into the pivotal Phase 3 study 281102 (NCT03393975) has been completed. The following criteria also applies to participants who completed study 281101 (NCT02216084), but did not participate in 281102 (NCT03393975).
Naïve participants and participants who were enrolled into the on-demand cohort of theTAK-755 Phase 3 pivotal study 281102 (NCT03393975) who meet ALL of the following criteria are eligible for this study:
- Participant is naïve or was enrolled into the on-demand cohort of the TAK-755 Phase 3 pivotal study 281102 (NCT03393975) for treatment of an acute TTP event but did not receive prophylactic treatment.
- Participant or legally authorized representative has provided signed informed consent (>=18 years of age) and/or assent form (<18 years of age).
- Participant is 0 to 70 years of age at the time of screening.
Participant has been diagnosed with severe congenital ADAMTS-13 deficiency defined as:
- Confirmed by molecular genetic testing, documented in participant history or at screening, and
- ADAMTS-13 activity <10% as measured by the fluorescence resonance energy transfer (FRETS)-VWF73 assay, documented in participant history or at screening. Participants currently receiving standard of care prophylactic therapy may exceed 10% ADAMTS-13 activity at screening.
- Participants currently receiving prophylactic therapy will be screened immediately prior to their usual prophylactic infusion.
- Participant does not display any severe TTP signs (platelet count <100,000/microliter (mcL) and elevation of LDH >2 × ULN) at screening (prophylactic cohort only).
- Participants >=16 years of age must have a Karnofsky score >=70% and participants <16 years of age must have a Lansky score >=80%.
- Participants is hepatitis C virus negative (HCV-) as confirmed by antibody or polymerase chain reaction testing OR HCV positive (HCV+) if their disease is chronic but stable.
- If female of childbearing potential, participant presents with a negative serum or urine pregnancy test confirmed not more than 7 days before the first IP administration and agrees to employ adequate birth control measures for the duration of the study and to undergo quarterly pregnancy testing.
- Sexually active males must use an accepted and effective method of contraception during treatment and until a minimum of 16 days after the last dose administered.
- Participant is willing and able to comply with the requirements of the protocol.
Participants from an Expanded Access Program or participants in Study 281102 (NCT03393975) who had an allergic reaction to standard of care prophylactic treatment must meet all of the following criteria:
Participants from an expanded access program as well as participants who participated in Study 281102(NCT03393975) who had an allergic reaction to standard-of-care prophylactic treatment are eligible for enrollment in the continuation study if they meet ALL of the following criteria.
- Participants or legally authorized representative has provided signed informed consent (>=18 years of age) and/or assent (<18 years of age).
- Participants is 0 to 70 years of age at the time of screening.
Participants has been diagnosed with severe congenital ADAMTS-13 deficiency defined as:
- Confirmed by molecular genetic testing, documented in participant history or at screening, and
- ADAMTS-13 activity <10% as measured by the fluorescence resonance energy transfer (FRETS)- VWF 73 assay, documented in participant history or at screening. Participants currently receiving standard of care prophylactic therapy may exceed 10% ADAMTS 13 activity at screening.
- Participant does not display any severe TTP signs (platelet count <100,000/mcL and elevation of LDH >2 × ULN) at screening (prophylactic cohort only).
- Participants >=16 years of age must have a Karnofsky score >=70% and participants <16 years of age must have a Lansky score >=80%.
- If female of childbearing potential, participant presents with a negative serum or urine pregnancy test confirmed not more than 7 days before the first IP administration and agrees to employ highly effective birth control measures for the duration of the study and to undergo quarterly pregnancy testing.
- Sexually active males must use an accepted and effective method of contraception during treatment and until a minimum of 16 days after the last dose administered.
- Participant is willing and able to comply with the requirements of the protocol.
Exclusion Criteria:
Participants who have completed TAK-755 Phase 3 pivotal study (281102) (NCT03393975) and naïve participants and non-naïve on-demand cohort participants and participants from an Expanded Access Program or participants in Study 281102 (NCT03393975) who had an allergic reaction to standard-of-care prophylactic treatment. The following criteria also applies to participants who completed study 281101 (NCT02216084), but did not participate in 281102 (NCT03393975).
- Participant has been diagnosed with any other TTP-like disorder (microangiopathic hemolytic anemia), including immune-mediated TTP.
- Known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS-13, hamster protein, or other constituents of TAK-755.
- Participant has a presence of a functional ADAMTS-13 inhibitor at screening.
- Participant has a medical history of a genetic or acquired immune deficiency that would interfere with the assessment of product immunogenicity, including participants who are human immunodeficiency virus-positive with an absolute cluster of differentiation 4 (CD4) count < 200/ cubic millimeter (mm^3) or who are receiving chronic immunosuppressive drugs.
- Participant has a history of significant neurological events, such as major stroke, indicating that a relapse might have severe consequences, as judged by the investigator.
- Participant has been diagnosed with severe cardiovascular disease (New York Heart Association classes 3 to 4).
- Participant with end stage renal disease requiring chronic dialysis.
Participant has been diagnosed with hepatic dysfunction, as evidenced by, but not limited to, any of the following:
- Serum alanine aminotransferase >= 2 × ULN
- Severe hypoalbuminemia <24 gram per liter (g/L)
- Portal vein hypertension (e.g., presence of otherwise unexplained splenomegaly, history of esophageal varices).
- In the opinion of the investigator, the participant has another clinically significant concomitant disease that may pose additional risks for the participant.
- Participant has been treated with an immunomodulatory drug, excluding topical treatment (e.g., ointments, nasal sprays), within 30 days prior to enrollment. Use of corticosteroids in conjunction with administration of fresh frozen plasma to prevent allergic reactions is permitted.
- Participant has an acute illness (e.g., influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, bronchial asthma) at the time of screening (prophylactic cohort only).
- Participant is receiving or anticipates receiving another investigational drug and/or interventional drug within 30 days before enrollment.
- Participant has a history of drug and/or alcohol abuse within the last 2 years.
- Participant has a progressive fatal disease and/or life expectancy of <= 3 months.
- Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures.
- Participant suffers from a mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study and/or evidence of an uncooperative attitude.
- Participant is a family member or employee of the sponsor or investigator.
- If female, participant is pregnant or lactating at the time of enrollment.
- In the UK only: Participants who have not previously received a dose of TAK-755.
Sites / Locations
- Childrens Healthcare of AtlantaRecruiting
- Roswell Park Comprehensive Cancer CenterRecruiting
- Duke University Medical CenterRecruiting
- Mid Ohio Heart Clinic IncRecruiting
- University of OklahomaRecruiting
- AKH - Medizinische Universität WienRecruiting
- Beijing Children's HospitalRecruiting
- Peking Union Medical College HospitalRecruiting
- Tongji Hospital Affiliated to Tongji Medicine UniversityRecruiting
- The First Affiliated Hospital of Soochow UniversityRecruiting
- Institute of Hematology and Hospital of Blood DiseaseRecruiting
- CHU Saint Etienne - Hôpital NordRecruiting
- Hôpital Necker - Enfants MaladesRecruiting
- Hôpital Saint-AntoineRecruiting
- Hôpital Robert Debré- ParisRecruiting
- Universitaetsklinikum Hamburg-EppendorfRecruiting
- Universitaetsklinikum Jena, Klinik fuerKinder-und JugendmedizinRecruiting
- Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)Recruiting
- Kyushu University HospitalRecruiting
- Hyogo College of Medicine HospitalRecruiting
- Medical Hospital,Tokyo Medical and Dental UniversityRecruiting
- Samodzielny Publiczny Dzieciecy Szpital KlinicznyRecruiting
- Instytut Hematologii i TransfuzjologiiRecruiting
- Complejo Hospitalario Universitario A CoruñaRecruiting
- Hospital de CrucesRecruiting
- Inselspital -Universitaetsspital BernRecruiting
- University College London Hospitals
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Prophylactic Cohort: TAK-755
On-Demand Cohort: TAK-755
Arm Description
All participants will receive prophylactic treatment with 40 IU/kg TAK-755 intravenous (IV) infusions once every week or once every other week for the duration of the study. Participants who are naïve will receive an initial IV dose of 40 IU/kg TAK-755 to allow measurement of the pharmacokinetics of TAK-755, followed by prophylactic treatment with 40 IU/kg TAK-755 by IV infusion once every week or once every other week for the duration of the study.
Participants will receive daily IV infusions of TAK-755 when experiencing an acute thrombotic thrombocytopenic purpura (TTP) event until 2 days after the acute TTP event is resolved. Participants will receive 40 IU/kg TAK-755 on the first day, followed by 20 IU/kg on Day 2, and then 15 IU/kg daily until 2 days after the acute TTP event has resolved. Upon resolution of the acute TTP event, participants may choose to move to the prophylactic cohort of the study or discontinue entirely from the study.
Outcomes
Primary Outcome Measures
Incidence of Related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
TEAE: any adverse event emerging or manifesting at or after the initiation of treatment with TAK-755 or any existing adverse event that worsens in either intensity or frequency following exposure to TAK-755. SAE: Signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event.
Secondary Outcome Measures
Number of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events in Participants with Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Undergoing Prophylactic Treatment with TAK-755
The number of acute TTP Events in participants with cTTP receiving prophylactic treatment with TAK-755 (rADAMTS13) will be assessed.
Incidence Rate of Acute TTP Events in Participants with cTTP Undergoing Prophylactic Treatment with TAK-755
Annualized acute TTP event incidence rate is calculated as the number of acute TTP events while receiving prophylactic treatment with TAK-755 (rADAMTS13) divided by the duration of the observation period in years. Annualized acute TTP event rate while participants are receiving prophylactic treatment with TAK-755 will be assessed.
Number of Acute TTP Events Resolved After Treatment with TAK-755 while Enrolled in the Study
Acute TTP events are considered resolved when: Platelet count is >=150,000/ μL or platelet count is within 25% of baseline and elevation of lactate dehydrogenase (LDH) <= 1.5 x baseline or <= 1.5 x upper limit of normal (ULN).
Proportion of Acute TTP Events Resolved After Treatment with TAK-755 while Enrolled in the Study
Proportion of acute TTP events that have resolved after treatment with TAK-755 (rADAMTS13) while enrolled in the study will be assessed. Acute TTP events are considered resolved when: Platelet count is >=150,000/ μL or platelet count is within 25% of baseline and elevation of LDH <= 1.5 x baseline or <= 1.5 x ULN.
Incidence of Acute TTP Events while Participants are on Their Final Dose and Dosing Regimen
Incidence of annualized acute TTP events while participants are on their final dose and dosing regimen will be assessed.
Time to Resolution of Acute TTP Events Following Treatment with IP
Time to resolution of acute TTP event is defined as the time from initial treatment of the event to resolution of the acute TTP event. Acute TTP events are considered resolved when: Platelet count is >=150,000/ μL or platelet count is within 25% of baseline and elevation of LDH <= 1.5 x baseline or <= 1.5 x ULN.
Total Quantity of TAK-755 Administered During the Treatment of Acute TTP Events
Total quantity of TAK-755 administered during the treatment of acute TTP events will be assessed. Acute events typically require 3-4 days of intensified treatment.
Incidence of Supplemental Doses Prompted by Subacute TTP Events
Incidence of supplemental doses prompted by subacute TTP events in the prophylactic cohort will be assessed.
Incidence of Dose Modifications Not Prompted by an Acute TTP Event
Incidence of dose modifications not prompted by an acute TTP event in the prophylactic cohort will be assessed.
Incidence of Thrombocytopenia
Thrombocytopenia is defined as a drop in platelet count >=25 percent (%) of baseline or a platelet count less than (<) 150,000/mcL. Incidence of thrombocytopenia in the prophylactic cohort will be assessed.
Incidence of Microangiopathic Hemolytic Anemia
Microangiopathic hemolytic anemia is defined as an elevation of LDH greater than (>) 1.5xbaseline or LDH > 1.5xULN. Incidence of microangiopathic hemolytic anemia in the prophylactic cohort will be assessed.
Incidence of Neurological Symptoms
Neurological symptoms include headache, confusion, dysphonia, dysarthria, focal or general motor symptoms including seizures. Incidence of neurological symptoms in the prophylactic cohort will be assessed.
Incidence of Renal Dysfunction
Renal dysfunction is defined as an increase in serum creatinine >1.5xbaseline. Incidence of renal dysfunction in the prophylactic cohort will be assessed.
incidence of Abdominal Pain
Incidence of abdominal pain in the prophylactic cohort will be assessed.
Incidence of TTP Manifestations for Participants Receiving TAK-755 as a Prophylactic Treatment
TTP manifestations are defined as a composite of thrombocytopenia, microangiopathic hemolytic anemia, and TTP-related signs/symptoms including but not limited to (renal signs, neurologic symptoms, fever, fatigue/lethargy and abdominal pain). Incidence of TTP manifestations in the prophylactic cohort will be assessed.
Incidence of TTP Manifestations While Receiving the Final Prophylactic Treatment Regimen with TAK-755 in the Home Setting
TTP manifestations are defined as a composite of thrombocytopenia, microangiopathic hemolytic anemia, and TTP-related signs/symptoms including but not limited to (renal signs, neurologic symptoms, fever, fatigue/lethargy and abdominal pain). Incidence of TTP manifestations in the prophylactic cohort in the home setting will be assessed.
Incidence of Acute TTP Events in Participants Receiving TAK-755 Prophylactically in the Home Setting
Incidence of acute TTP events in participants receiving TAK-755 prophylactically in the home setting will be assessed.
Incidence of all AEs and SAEs (Including Unrelated)
AE: any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this IP or medicinal product. SAE: Signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event.
Proportion of Participants with anti-ADAMTS13 Binding Antibodies and Neutralizing Antibodies Following ADAMTS13 Administration
Proportion of participants with anti-ADAMTS13 binding antibodies and neutralizing antibodies following ADAMTS13 administration will be assessed.
Number of Participants Experiencing TAK-755 Related AEs and SAEs After Receiving TAK-755 in the Home Setting
AE: Any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. SAE: Signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event.
Number of Participants with AEs and SAEs After Receiving TAK-755 in the Home Setting
AE: Any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. SAE: Signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event.
Health Related Quality of Life (HRQoL): cTTP-Specific Patient reported outcomes (PROs)
The cTTP specific patient-reported outcomes (PRO) instrument consists of 26 questions designed to assess the participants experience of fatigue, joint, muscle, abdominal and chest pain in the previous 24 hours, neurologic manifestations, bruising, feelings of depression and mood alterations, and activity limitation in the past 7 days, and participants attitudes, experienced side effects, work/school absences and travel impact associated with treatment received for TTP during the previous 2 weeks. The cTTP PRO assessment is focused on measuring the symptoms and impacts of the disease. The scores range from 0 to 152. Higher scores indicate a better quality of life.
HRQoL: 36-Item Short Form Health Survey (SF-36)
The SF-36 is a generic quality-of-life instrument that has been widely used to assess HRQoL of participants. Generic instruments are used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQoL.
HRQoL: Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9)
TSQM is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. TSQM-9 is a 9-item, validated, self-administered instrument used to assess participant's satisfaction with medication. The three domains assessed are effectiveness, convenience, and global satisfaction. The score of each of the 3 domains is based on an algorithm to create a score of 0 to 100. Higher score indicated greater satisfaction in that domain.
HRQoL: EuroQol 5 Dimensions Questionnaire 3-Level (EQ-5D-3L)
EQ-5D-3L health questionnaire is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.
HRQoL: EQ-5D-youth (EQ-5D-Y)
EQ-5D-Y health questionnaire is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.
HRQoL: Pediatric Quality of Life Inventory (Peds QL)
The Peds QL is a generic health related quality of life instrument designed specifically for a pediatric population and captures following domains: physical functioning, emotional functioning, social functioning, school functioning, psychosocial summary, physical health and total score. The Peds-QL total score consist of all 23 items of all domains. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better quality of life.
HRQoL: Infusion Experience Satisfaction Assessment Questionnaire
Infusion experience satisfaction assessment questionnaire will assess participant satisfaction on various aspects of the infusion experience (i.e., Convenience, impact on daily life, comfort in the treatment environment, time invested to receive infusion, concerns on handling potential complications, interaction with members of health care team and with other participants). Each item is rated on a 5-point scale from 1 (very poor) to 5 (very good) with a total score ranging from 93 to 465. Higher scores indicate greater satisfaction.
Resource Utilization: Length of Hospital Stay for Acute TTP Events
Number of days of participants stay in hospital for acute TTP events will be assessed.
Resource Utilization: Number of Hospitalizations for Acute TTP Events
Number of hospitalizations for acute TTP events will be assessed.
Resource Utilization: Number of Participants with Healthcare Resource Utilization During Prophylaxis
Health care resource utilization including days missed from school/work due to TTP-related illness will be assessed for the prophylactic cohort.
Resource Utilization: Number of Participants with Days Missed From School or Work due to TTP-Related Illness
Number of participants with days missed from school or work due to TTP-related illness will be assessed.
Assessment of Trough and Postdose ADAMTS13 Activity: Antigen Levels (Activity:Ag)
Trough and postdose ADAMTS13 activity and antigen levels from participants in prophylactic and on-demand cohorts during the study and during acute and subacute TTP events will be assessed.
Assessment of Von Willebrand Factor: Antigen (VWF:Ag)
VWF:Ag is a measure of total VWF protein and will be assessed using a sandwich enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human-VWF antibodies. Assessments of VWF:Ag at baseline and following infusion of the TAK-755 treatment during the initial PK assessment in prophylactic and on-demand cohorts and during acute TTP events will be reported.
Assessment of Von Willebrand Factor: Ristocetin Cofactor Activity (VWF:RCo)
VWF:RCo will provide a measure of the ability of VWF to bind platelet glycoprotein Ib. Stabilized platelets are agglutinated in the presence of VWF and the antibiotic Ristocetin. Assessments of VWF:RCo during the study from participants in both the on-demand cohorts and during acute events will be reported.
Assessment of VWF:Ag in Relation to ADAMTS13 Activity Levels
VWF:Ag is a measure of total VWF protein and will be assessed using a sandwich ELISA employing polyclonal anti-human-VWF antibodies. Longitudinal relationship of observed ADAMTS13 activity levels and VWF:Ag following infusion of the TAK-755 treatment during the initial PK assessment will be assessed (for TAK-755 naïve participants only).
Assessment of VWF:RCo in Relation to ADAMTS13 Activity Levels
VWF:RCo will provide a measure of the ability of VWF to bind platelet glycoprotein Ib. Stabilized platelets are agglutinated in the presence of VWF and the antibiotic Ristocetin. Longitudinal relationship of observed ADAMTS13 activity levels and VWF:RCo following infusion of the TAK-755 treatment during the initial PK assessment will be assessed (for TAK-755 naïve participants only).
Number of Participants with Acute and Subacute Events in Relation with ADAMTS13 Activity Levels
Longitudinal relationship of ADAMTS13 activity levels and participants with acute and subacute TTP events will be assessed.
Full Information
NCT ID
NCT04683003
First Posted
December 10, 2020
Last Updated
May 19, 2023
Sponsor
Takeda
Collaborators
Takeda Development Center Americas, Inc., Shire
1. Study Identification
Unique Protocol Identification Number
NCT04683003
Brief Title
A Study of TAK-755 in Participants With Congenital Thrombotic Thrombocytopenic Purpura
Official Title
A Phase 3b, Prospective, Open-label, Multicenter, Single Treatment Arm, Continuation Study of the Safety and Efficacy of TAK-755 (rADAMTS13, Also Known as BAX 930/SHP655) in the Prophylactic and On-demand Treatment of Subjects With Severe Congenital Thrombotic Thrombocytopenic Purpura (cTTP; Upshaw-Schulman Syndrome, or Hereditary Thrombotic Thrombocytopenic Purpura)
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 14, 2021 (Actual)
Primary Completion Date
August 27, 2026 (Anticipated)
Study Completion Date
August 27, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Takeda
Collaborators
Takeda Development Center Americas, Inc., Shire
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Thrombotic thrombocytopenic purpura (or TTP for short) is a condition where blood clots form in small blood vessels throughout the body. The clots can limit or block the flow of oxygen-rich blood to the body's organs, such as the brain, kidneys, and heart. As a result, serious health problems can develop. The increased clotting that occurs in TTP uses up the cells that help the blood to clot, called platelets. With fewer platelets available in the blood, bleeding problems can also occur. People who have TTP may bleed underneath the skin forming purple bruises, or purpura. TTP also can cause anemia, a condition in which red blood cells break apart faster than the body can replace them, leading to fewer red blood cells than in normal.
TTP is caused by a lack of activity in the ADAMTS13 enzyme, a protein in the blood involved in controlling clotting of the blood. The ADAMTS13 enzyme breaks up another blood protein called von Willebrand factor that forms blood clots by clumping together with platelets. Some people are born with this condition, while others develop the condition during their life. Many people who are born with TTP experience frequent flare-ups that need to be treated right away. TAK-755 is a medicine that replaces ADAMTS13 and may prevent or control TTP flare-ups, called acute TTP events.
The main aim of the study is to check for side effects of long-term treatment with TAK-755. Treatment will be given in 2 ways:
TAK-755 treatment given either every week or every other week to prevent acute TTP events from happening (the "prophylactic" cohort).
TAK-755 treatment given to control an acute TTP event when it happens (the "on-demand" cohort).
Participants in the prophylactic cohort will receive treatment in the clinic or at home for up to approximately 3 years. They will visit the clinic at least every 12 weeks. Participants in the on-demand cohort will receive daily treatment for the acute TTP event until the flare-up has gotten better. They will have a follow-up visit at the clinic 4 weeks later.
Detailed Description
This is a follow-up study to the Phase 3 pivotal study (281102 [NCT03393975]) and will be comprised of two treatment cohorts (Prophylactic and On-demand) consisting of naïve and non-naïve participants who were born with TTP, with a total duration of approximately 6 years. A maximum of approximately 77 participants will be enrolled in this study (approximately 57 participants who have completed study 281102 [NCT03393975] [non-naïve participants] and at least 20 naïve participants (participants who are naïve to TAK-755). Participants from Expanded Access Programs, participants from study 281102 (NCT03393975) who had an allergic reaction to standard of care treatment, and participants who completed the Phase 1 study (281101 [NCT02216084]) but did not participate in Study 281102, will also be eligible for enrollment in this continuation study as naïve participants.
TAK-755 is given slowly through a vein (intravenous infusion). Participants in the prophylactic cohort will be able to opt for treatment in a home setting by caregiver or self-infusion subject to conditions and to local regulatory approval.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Thrombotic Thrombocytopenic Purpura (TTP)
Keywords
Congenital Thrombotic Thrombocytopenic Purpura (TTP)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
77 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Prophylactic Cohort: TAK-755
Arm Type
Experimental
Arm Description
All participants will receive prophylactic treatment with 40 IU/kg TAK-755 intravenous (IV) infusions once every week or once every other week for the duration of the study.
Participants who are naïve will receive an initial IV dose of 40 IU/kg TAK-755 to allow measurement of the pharmacokinetics of TAK-755, followed by prophylactic treatment with 40 IU/kg TAK-755 by IV infusion once every week or once every other week for the duration of the study.
Arm Title
On-Demand Cohort: TAK-755
Arm Type
Experimental
Arm Description
Participants will receive daily IV infusions of TAK-755 when experiencing an acute thrombotic thrombocytopenic purpura (TTP) event until 2 days after the acute TTP event is resolved.
Participants will receive 40 IU/kg TAK-755 on the first day, followed by 20 IU/kg on Day 2, and then 15 IU/kg daily until 2 days after the acute TTP event has resolved. Upon resolution of the acute TTP event, participants may choose to move to the prophylactic cohort of the study or discontinue entirely from the study.
Intervention Type
Biological
Intervention Name(s)
TAK-755
Other Intervention Name(s)
rADAMTS13; recombinant ADAMTS13; SHP-655; BAX 930
Intervention Description
TAK-755 IV infusion
Primary Outcome Measure Information:
Title
Incidence of Related Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
TEAE: any adverse event emerging or manifesting at or after the initiation of treatment with TAK-755 or any existing adverse event that worsens in either intensity or frequency following exposure to TAK-755. SAE: Signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event.
Time Frame
Throughout the study period of approximately 6 years
Secondary Outcome Measure Information:
Title
Number of Acute Thrombotic Thrombocytopenic Purpura (TTP) Events in Participants with Congenital Thrombotic Thrombocytopenic Purpura (cTTP) Undergoing Prophylactic Treatment with TAK-755
Description
The number of acute TTP Events in participants with cTTP receiving prophylactic treatment with TAK-755 (rADAMTS13) will be assessed.
Time Frame
Up to approximately 3 years
Title
Incidence Rate of Acute TTP Events in Participants with cTTP Undergoing Prophylactic Treatment with TAK-755
Description
Annualized acute TTP event incidence rate is calculated as the number of acute TTP events while receiving prophylactic treatment with TAK-755 (rADAMTS13) divided by the duration of the observation period in years. Annualized acute TTP event rate while participants are receiving prophylactic treatment with TAK-755 will be assessed.
Time Frame
Up to approximately 3 years
Title
Number of Acute TTP Events Resolved After Treatment with TAK-755 while Enrolled in the Study
Description
Acute TTP events are considered resolved when: Platelet count is >=150,000/ μL or platelet count is within 25% of baseline and elevation of lactate dehydrogenase (LDH) <= 1.5 x baseline or <= 1.5 x upper limit of normal (ULN).
Time Frame
Throughout the study period of approximately 6 years
Title
Proportion of Acute TTP Events Resolved After Treatment with TAK-755 while Enrolled in the Study
Description
Proportion of acute TTP events that have resolved after treatment with TAK-755 (rADAMTS13) while enrolled in the study will be assessed. Acute TTP events are considered resolved when: Platelet count is >=150,000/ μL or platelet count is within 25% of baseline and elevation of LDH <= 1.5 x baseline or <= 1.5 x ULN.
Time Frame
Throughout the study period of approximately 6 years
Title
Incidence of Acute TTP Events while Participants are on Their Final Dose and Dosing Regimen
Description
Incidence of annualized acute TTP events while participants are on their final dose and dosing regimen will be assessed.
Time Frame
Throughout the study period of approximately 6 years
Title
Time to Resolution of Acute TTP Events Following Treatment with IP
Description
Time to resolution of acute TTP event is defined as the time from initial treatment of the event to resolution of the acute TTP event. Acute TTP events are considered resolved when: Platelet count is >=150,000/ μL or platelet count is within 25% of baseline and elevation of LDH <= 1.5 x baseline or <= 1.5 x ULN.
Time Frame
Throughout the study period of approximately 6 years
Title
Total Quantity of TAK-755 Administered During the Treatment of Acute TTP Events
Description
Total quantity of TAK-755 administered during the treatment of acute TTP events will be assessed. Acute events typically require 3-4 days of intensified treatment.
Time Frame
Throughout the study period of approximately 6 years
Title
Incidence of Supplemental Doses Prompted by Subacute TTP Events
Description
Incidence of supplemental doses prompted by subacute TTP events in the prophylactic cohort will be assessed.
Time Frame
Up to approximately 3 years
Title
Incidence of Dose Modifications Not Prompted by an Acute TTP Event
Description
Incidence of dose modifications not prompted by an acute TTP event in the prophylactic cohort will be assessed.
Time Frame
Up to approximately 3 years
Title
Incidence of Thrombocytopenia
Description
Thrombocytopenia is defined as a drop in platelet count >=25 percent (%) of baseline or a platelet count less than (<) 150,000/mcL. Incidence of thrombocytopenia in the prophylactic cohort will be assessed.
Time Frame
Up to approximately 3 years
Title
Incidence of Microangiopathic Hemolytic Anemia
Description
Microangiopathic hemolytic anemia is defined as an elevation of LDH greater than (>) 1.5xbaseline or LDH > 1.5xULN. Incidence of microangiopathic hemolytic anemia in the prophylactic cohort will be assessed.
Time Frame
Up to approximately 3 years
Title
Incidence of Neurological Symptoms
Description
Neurological symptoms include headache, confusion, dysphonia, dysarthria, focal or general motor symptoms including seizures. Incidence of neurological symptoms in the prophylactic cohort will be assessed.
Time Frame
Up to approximately 3 years
Title
Incidence of Renal Dysfunction
Description
Renal dysfunction is defined as an increase in serum creatinine >1.5xbaseline. Incidence of renal dysfunction in the prophylactic cohort will be assessed.
Time Frame
Up to approximately 3 years
Title
incidence of Abdominal Pain
Description
Incidence of abdominal pain in the prophylactic cohort will be assessed.
Time Frame
Up to approximately 3 years
Title
Incidence of TTP Manifestations for Participants Receiving TAK-755 as a Prophylactic Treatment
Description
TTP manifestations are defined as a composite of thrombocytopenia, microangiopathic hemolytic anemia, and TTP-related signs/symptoms including but not limited to (renal signs, neurologic symptoms, fever, fatigue/lethargy and abdominal pain). Incidence of TTP manifestations in the prophylactic cohort will be assessed.
Time Frame
Up to approximately 3 years
Title
Incidence of TTP Manifestations While Receiving the Final Prophylactic Treatment Regimen with TAK-755 in the Home Setting
Description
TTP manifestations are defined as a composite of thrombocytopenia, microangiopathic hemolytic anemia, and TTP-related signs/symptoms including but not limited to (renal signs, neurologic symptoms, fever, fatigue/lethargy and abdominal pain). Incidence of TTP manifestations in the prophylactic cohort in the home setting will be assessed.
Time Frame
Up to approximately 3 years
Title
Incidence of Acute TTP Events in Participants Receiving TAK-755 Prophylactically in the Home Setting
Description
Incidence of acute TTP events in participants receiving TAK-755 prophylactically in the home setting will be assessed.
Time Frame
Up to approximately 3 years
Title
Incidence of all AEs and SAEs (Including Unrelated)
Description
AE: any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this IP or medicinal product. SAE: Signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event.
Time Frame
Throughout the study period of approximately 6 years
Title
Proportion of Participants with anti-ADAMTS13 Binding Antibodies and Neutralizing Antibodies Following ADAMTS13 Administration
Description
Proportion of participants with anti-ADAMTS13 binding antibodies and neutralizing antibodies following ADAMTS13 administration will be assessed.
Time Frame
Throughout the study period of approximately 6 years
Title
Number of Participants Experiencing TAK-755 Related AEs and SAEs After Receiving TAK-755 in the Home Setting
Description
AE: Any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. SAE: Signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event.
Time Frame
Throughout the study period of approximately 6 years
Title
Number of Participants with AEs and SAEs After Receiving TAK-755 in the Home Setting
Description
AE: Any untoward medical occurrence in a participant administered IP that does not necessarily have a causal relationship with the treatment. SAE: Signs, symptoms or outcomes which results in death, requires inpatient hospitalization or prolongation of hospitalization, results in persistent or significant disability/incapacity, results in a congenital abnormality/birth defect, or is an important medical event.
Time Frame
Throughout the study period of approximately 6 years
Title
Health Related Quality of Life (HRQoL): cTTP-Specific Patient reported outcomes (PROs)
Description
The cTTP specific patient-reported outcomes (PRO) instrument consists of 26 questions designed to assess the participants experience of fatigue, joint, muscle, abdominal and chest pain in the previous 24 hours, neurologic manifestations, bruising, feelings of depression and mood alterations, and activity limitation in the past 7 days, and participants attitudes, experienced side effects, work/school absences and travel impact associated with treatment received for TTP during the previous 2 weeks. The cTTP PRO assessment is focused on measuring the symptoms and impacts of the disease. The scores range from 0 to 152. Higher scores indicate a better quality of life.
Time Frame
Throughout the study period of approximately 6 years
Title
HRQoL: 36-Item Short Form Health Survey (SF-36)
Description
The SF-36 is a generic quality-of-life instrument that has been widely used to assess HRQoL of participants. Generic instruments are used in general populations to assess a wide range of domains applicable to a variety of health states, conditions, and diseases. The SF-36 consists of 36 items that are aggregated into 8 multi-item scales (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health), with scores ranging from 0 to 100. Higher scores indicate better HRQoL.
Time Frame
Throughout the study period of approximately 6 years
Title
HRQoL: Abbreviated 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9)
Description
TSQM is a global satisfaction scale used to assess the overall level of participant's satisfaction or dissatisfaction with their medications. TSQM-9 is a 9-item, validated, self-administered instrument used to assess participant's satisfaction with medication. The three domains assessed are effectiveness, convenience, and global satisfaction. The score of each of the 3 domains is based on an algorithm to create a score of 0 to 100. Higher score indicated greater satisfaction in that domain.
Time Frame
Throughout the study period of approximately 6 years
Title
HRQoL: EuroQol 5 Dimensions Questionnaire 3-Level (EQ-5D-3L)
Description
EQ-5D-3L health questionnaire is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.
Time Frame
Throughout the study period of approximately 6 years
Title
HRQoL: EQ-5D-youth (EQ-5D-Y)
Description
EQ-5D-Y health questionnaire is a participant answered questionnaire scoring 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D total score ranges from 0 (worst health state) to 1 (perfect health state) and 1 reflects the best outcome.
Time Frame
Throughout the study period of approximately 6 years
Title
HRQoL: Pediatric Quality of Life Inventory (Peds QL)
Description
The Peds QL is a generic health related quality of life instrument designed specifically for a pediatric population and captures following domains: physical functioning, emotional functioning, social functioning, school functioning, psychosocial summary, physical health and total score. The Peds-QL total score consist of all 23 items of all domains. This modular instrument uses a 5-point scale: from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores indicate better quality of life.
Time Frame
Throughout the study period of approximately 6 years
Title
HRQoL: Infusion Experience Satisfaction Assessment Questionnaire
Description
Infusion experience satisfaction assessment questionnaire will assess participant satisfaction on various aspects of the infusion experience (i.e., Convenience, impact on daily life, comfort in the treatment environment, time invested to receive infusion, concerns on handling potential complications, interaction with members of health care team and with other participants). Each item is rated on a 5-point scale from 1 (very poor) to 5 (very good) with a total score ranging from 93 to 465. Higher scores indicate greater satisfaction.
Time Frame
Throughout the study period of approximately 6 years
Title
Resource Utilization: Length of Hospital Stay for Acute TTP Events
Description
Number of days of participants stay in hospital for acute TTP events will be assessed.
Time Frame
Throughout the study period of approximately 6 years
Title
Resource Utilization: Number of Hospitalizations for Acute TTP Events
Description
Number of hospitalizations for acute TTP events will be assessed.
Time Frame
Throughout the study period of approximately 6 years
Title
Resource Utilization: Number of Participants with Healthcare Resource Utilization During Prophylaxis
Description
Health care resource utilization including days missed from school/work due to TTP-related illness will be assessed for the prophylactic cohort.
Time Frame
Up to approximately 3 years
Title
Resource Utilization: Number of Participants with Days Missed From School or Work due to TTP-Related Illness
Description
Number of participants with days missed from school or work due to TTP-related illness will be assessed.
Time Frame
Throughout the study period of approximately 6 years
Title
Assessment of Trough and Postdose ADAMTS13 Activity: Antigen Levels (Activity:Ag)
Description
Trough and postdose ADAMTS13 activity and antigen levels from participants in prophylactic and on-demand cohorts during the study and during acute and subacute TTP events will be assessed.
Time Frame
At trough (for acute events) and within 72 hours pre-infusion and 65 minutes post-infusion (for both acute and subacute) at interval study visits every 12 weeks (up to 6 years)
Title
Assessment of Von Willebrand Factor: Antigen (VWF:Ag)
Description
VWF:Ag is a measure of total VWF protein and will be assessed using a sandwich enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human-VWF antibodies. Assessments of VWF:Ag at baseline and following infusion of the TAK-755 treatment during the initial PK assessment in prophylactic and on-demand cohorts and during acute TTP events will be reported.
Time Frame
At trough pre-infusion and 65 minutes post-infusion at interval study visits every 12 weeks (up to 6 years)
Title
Assessment of Von Willebrand Factor: Ristocetin Cofactor Activity (VWF:RCo)
Description
VWF:RCo will provide a measure of the ability of VWF to bind platelet glycoprotein Ib. Stabilized platelets are agglutinated in the presence of VWF and the antibiotic Ristocetin. Assessments of VWF:RCo during the study from participants in both the on-demand cohorts and during acute events will be reported.
Time Frame
At trough pre-infusion and 65 minutes post-infusion at interval study visits every 12 weeks (up to 6 years)
Title
Assessment of VWF:Ag in Relation to ADAMTS13 Activity Levels
Description
VWF:Ag is a measure of total VWF protein and will be assessed using a sandwich ELISA employing polyclonal anti-human-VWF antibodies. Longitudinal relationship of observed ADAMTS13 activity levels and VWF:Ag following infusion of the TAK-755 treatment during the initial PK assessment will be assessed (for TAK-755 naïve participants only).
Time Frame
At trough (for acute events) and within 72 hours pre-infusion and 65 minutes post-infusion (for both acute and subacute) at interval study visits every 12 weeks (up to 6 years)
Title
Assessment of VWF:RCo in Relation to ADAMTS13 Activity Levels
Description
VWF:RCo will provide a measure of the ability of VWF to bind platelet glycoprotein Ib. Stabilized platelets are agglutinated in the presence of VWF and the antibiotic Ristocetin. Longitudinal relationship of observed ADAMTS13 activity levels and VWF:RCo following infusion of the TAK-755 treatment during the initial PK assessment will be assessed (for TAK-755 naïve participants only).
Time Frame
At trough (for acute events) and within 72 hours pre-infusion and 65 minutes post-infusion (for both acute and subacute) at interval study visits every 12 weeks (up to 6 years)
Title
Number of Participants with Acute and Subacute Events in Relation with ADAMTS13 Activity Levels
Description
Longitudinal relationship of ADAMTS13 activity levels and participants with acute and subacute TTP events will be assessed.
Time Frame
At trough (for acute events) and within 72 hours pre-infusion and 65 minutes post-infusion (for both acute and subacute) at interval study visits every 12 weeks (up to 6 years)
10. Eligibility
Sex
All
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participants who have completed TAK-755 Phase 3 pivotal Study 281102 (NCT03393975) in the prophylactic cohort and who meet all of the following criteria are eligible for this study:
Participants or legally authorized representative has provided signed informed consent >=18 years of age and/or assent form <18 years of age.
Participant 0 to 70 years of age at the time of screening of the 281102 (NCT03393975) study.
Participant has been diagnosed with severe congenital ADAMTS-13 deficiency.
Participant does not display any severe thrombotic thrombocytopenic purpura (TTP) signs (platelet count <100,000/ microliter (mcL) and elevation of lactate dehydrogenase (LDH) greater than (>) 2 × ULN at screening (prophylactic cohort only).
Participants >=16 years of age must have a Karnofsky score >= 70% and participants <16 years of age must have a Lansky score >=80%.
If female of childbearing potential, participant presents with a negative serum or urine pregnancy test confirmed not more than 7 days before the first IP administration and agrees to employ adequate birth control measures for the duration of the study and to undergo quarterly pregnancy testing.
Sexually active males must use an accepted and effective method of contraception during the treatment and until a minimum of 16 days after the last dose administered.
Participant is willing and able to comply with the requirements of the protocol.
All naïve participants and non-naïve on-demand cohort participants:
Naïve participants can only be enrolled in this continuation after enrollment of the adult participants in the prophylactic arm of TAK-755 Phase 3 pivotal study 281102 (NCT03393975) has been completed. Naïve pediatric participants can be enrolled after enrollment of the respective age cohort into the pivotal Phase 3 study 281102 (NCT03393975) has been completed. The following criteria also applies to participants who completed study 281101 (NCT02216084), but did not participate in 281102 (NCT03393975).
Naïve participants and participants who were enrolled into the on-demand cohort of theTAK-755 Phase 3 pivotal study 281102 (NCT03393975) who meet ALL of the following criteria are eligible for this study:
Participant is naïve or was enrolled into the on-demand cohort of the TAK-755 Phase 3 pivotal study 281102 (NCT03393975) for treatment of an acute TTP event but did not receive prophylactic treatment.
Participant or legally authorized representative has provided signed informed consent (>=18 years of age) and/or assent form (<18 years of age).
Participant is 0 to 70 years of age at the time of screening.
Participant has been diagnosed with severe congenital ADAMTS-13 deficiency defined as:
Confirmed by molecular genetic testing, documented in participant history or at screening, and
ADAMTS-13 activity <10% as measured by the fluorescence resonance energy transfer (FRETS)-VWF73 assay, documented in participant history or at screening. Participants currently receiving standard of care prophylactic therapy may exceed 10% ADAMTS-13 activity at screening.
Participants currently receiving prophylactic therapy will be screened immediately prior to their usual prophylactic infusion.
Participant does not display any severe TTP signs (platelet count <100,000/microliter (mcL) and elevation of LDH >2 × ULN) at screening (prophylactic cohort only).
Participants >=16 years of age must have a Karnofsky score >=70% and participants <16 years of age must have a Lansky score >=80%.
Participants is hepatitis C virus negative (HCV-) as confirmed by antibody or polymerase chain reaction testing OR HCV positive (HCV+) if their disease is chronic but stable.
If female of childbearing potential, participant presents with a negative serum or urine pregnancy test confirmed not more than 7 days before the first IP administration and agrees to employ adequate birth control measures for the duration of the study and to undergo quarterly pregnancy testing.
Sexually active males must use an accepted and effective method of contraception during treatment and until a minimum of 16 days after the last dose administered.
Participant is willing and able to comply with the requirements of the protocol.
Participants from an Expanded Access Program or participants in Study 281102 (NCT03393975) who had an allergic reaction to standard of care prophylactic treatment must meet all of the following criteria:
Participants from an expanded access program as well as participants who participated in Study 281102(NCT03393975) who had an allergic reaction to standard-of-care prophylactic treatment are eligible for enrollment in the continuation study if they meet ALL of the following criteria.
Participants or legally authorized representative has provided signed informed consent (>=18 years of age) and/or assent (<18 years of age).
Participants is 0 to 70 years of age at the time of screening.
Participants has been diagnosed with severe congenital ADAMTS-13 deficiency defined as:
Confirmed by molecular genetic testing, documented in participant history or at screening, and
ADAMTS-13 activity <10% as measured by the fluorescence resonance energy transfer (FRETS)- VWF 73 assay, documented in participant history or at screening. Participants currently receiving standard of care prophylactic therapy may exceed 10% ADAMTS 13 activity at screening.
Participant does not display any severe TTP signs (platelet count <100,000/mcL and elevation of LDH >2 × ULN) at screening (prophylactic cohort only).
Participants >=16 years of age must have a Karnofsky score >=70% and participants <16 years of age must have a Lansky score >=80%.
If female of childbearing potential, participant presents with a negative serum or urine pregnancy test confirmed not more than 7 days before the first IP administration and agrees to employ highly effective birth control measures for the duration of the study and to undergo quarterly pregnancy testing.
Sexually active males must use an accepted and effective method of contraception during treatment and until a minimum of 16 days after the last dose administered.
Participant is willing and able to comply with the requirements of the protocol.
Exclusion Criteria:
Participants who have completed TAK-755 Phase 3 pivotal study (281102) (NCT03393975) and naïve participants and non-naïve on-demand cohort participants and participants from an Expanded Access Program or participants in Study 281102 (NCT03393975) who had an allergic reaction to standard-of-care prophylactic treatment. The following criteria also applies to participants who completed study 281101 (NCT02216084), but did not participate in 281102 (NCT03393975).
Participant has been diagnosed with any other TTP-like disorder (microangiopathic hemolytic anemia), including immune-mediated TTP.
Known life-threatening hypersensitivity reaction, including anaphylaxis, to the parent molecule ADAMTS-13, hamster protein, or other constituents of TAK-755.
Participant has a presence of a functional ADAMTS-13 inhibitor at screening.
Participant has a medical history of a genetic or acquired immune deficiency that would interfere with the assessment of product immunogenicity, including participants who are human immunodeficiency virus-positive with an absolute cluster of differentiation 4 (CD4) count < 200/ cubic millimeter (mm^3) or who are receiving chronic immunosuppressive drugs.
Participant has a history of significant neurological events, such as major stroke, indicating that a relapse might have severe consequences, as judged by the investigator.
Participant has been diagnosed with severe cardiovascular disease (New York Heart Association classes 3 to 4).
Participant with end stage renal disease requiring chronic dialysis.
Participant has been diagnosed with hepatic dysfunction, as evidenced by, but not limited to, any of the following:
Serum alanine aminotransferase >= 2 × ULN
Severe hypoalbuminemia <24 gram per liter (g/L)
Portal vein hypertension (e.g., presence of otherwise unexplained splenomegaly, history of esophageal varices).
In the opinion of the investigator, the participant has another clinically significant concomitant disease that may pose additional risks for the participant.
Participant has been treated with an immunomodulatory drug, excluding topical treatment (e.g., ointments, nasal sprays), within 30 days prior to enrollment. Use of corticosteroids in conjunction with administration of fresh frozen plasma to prevent allergic reactions is permitted.
Participant has an acute illness (e.g., influenza, flu-like syndrome, allergic rhinitis/conjunctivitis, bronchial asthma) at the time of screening (prophylactic cohort only).
Participant is receiving or anticipates receiving another investigational drug and/or interventional drug within 30 days before enrollment.
Participant has a history of drug and/or alcohol abuse within the last 2 years.
Participant has a progressive fatal disease and/or life expectancy of <= 3 months.
Participant is identified by the investigator as being unable or unwilling to cooperate with study procedures.
Participant suffers from a mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study and/or evidence of an uncooperative attitude.
Participant is a family member or employee of the sponsor or investigator.
If female, participant is pregnant or lactating at the time of enrollment.
In the UK only: Participants who have not previously received a dose of TAK-755.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Takeda Contact
Phone
+1-877-825-3327
Email
medinfoUS@takeda.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Takeda
Official's Role
Study Director
Facility Information:
Facility Name
Childrens Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
404-727-1608
Email
ana.antun@emoryhealthcare.org
First Name & Middle Initial & Last Name & Degree
Ana Antun
Facility Name
Roswell Park Comprehensive Cancer Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site contact
Phone
716-845-2333
Email
clare.twist@roswellpark.org
First Name & Middle Initial & Last Name & Degree
Clare Twist
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
919-660-7050
Email
thomas.ortel@duke.edu
First Name & Middle Initial & Last Name & Degree
Thomas Ortel
Facility Name
Mid Ohio Heart Clinic Inc
City
Dublin
State/Province
Ohio
ZIP/Postal Code
43017
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
614-293-2887
Email
spero.cataland@osumc.edu
First Name & Middle Initial & Last Name & Degree
Spero Cataland
Facility Name
University of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
405-271-8299
Email
sami-ibrahami@ouhsc.edu
First Name & Middle Initial & Last Name & Degree
Sami Ibrahimi
Facility Name
AKH - Medizinische Universität Wien
City
Vienna
ZIP/Postal Code
1090
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+4314040044100
Email
paul.knoebl@meduniwien.ac.at
First Name & Middle Initial & Last Name & Degree
Paul Knoebl
Facility Name
Beijing Children's Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100045
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site contact
Phone
8613911383480
Email
wurunhuigcp@163.com
First Name & Middle Initial & Last Name & Degree
Runhui Wu
Facility Name
Peking Union Medical College Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100730
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
8618612671897
Email
xiaojuan@pumch.cn
First Name & Middle Initial & Last Name & Degree
Juan Xiao
Facility Name
Tongji Hospital Affiliated to Tongji Medicine University
City
Wuhan
State/Province
Hubei
ZIP/Postal Code
430030
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site contact
Phone
8618971353983
Email
qunhu2013@163.com
First Name & Middle Initial & Last Name & Degree
Qun Hu
Facility Name
The First Affiliated Hospital of Soochow University
City
SuZhou
State/Province
Jiangsushe
ZIP/Postal Code
215006
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site contact
Phone
8613913518032
Email
yuziqiang@suda.edu.cn
First Name & Middle Initial & Last Name & Degree
Ziqiang Yu
Facility Name
Institute of Hematology and Hospital of Blood Disease
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300021
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site contact
Phone
8613920673951
Email
xuefeng@ihcams.ac.cn
First Name & Middle Initial & Last Name & Degree
Feng Xue
Facility Name
CHU Saint Etienne - Hôpital Nord
City
Saint-Priest-en-Jarez cedex
State/Province
Loire
ZIP/Postal Code
42270
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+33477828038
Email
claire.berger@chu-st-etienne.fr
First Name & Middle Initial & Last Name & Degree
Claire Berger
Facility Name
Hôpital Necker - Enfants Malades
City
Paris cedex 15
State/Province
Paris
ZIP/Postal Code
75015
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+33144497210
Email
nathalie.biebuyck@aphp.fr
First Name & Middle Initial & Last Name & Degree
Nathalie Biebuyck
Facility Name
Hôpital Saint-Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+33149282162
Email
paul.coppo@aphp.fr
First Name & Middle Initial & Last Name & Degree
Paul Coppo
Facility Name
Hôpital Robert Debré- Paris
City
Paris
ZIP/Postal Code
75935
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+33140032467
Email
claire.dossir@aphp.fr
First Name & Middle Initial & Last Name & Degree
Claire Dossier
Facility Name
Universitaetsklinikum Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+4940741053796
Email
hassenpflug@uke.de
First Name & Middle Initial & Last Name & Degree
Wolf-Achim Hassenpflug
Facility Name
Universitaetsklinikum Jena, Klinik fuerKinder-und Jugendmedizin
City
Jena
ZIP/Postal Code
07747
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+493641938426
Email
karim.kentouche@med.uni-jena.de
First Name & Middle Initial & Last Name & Degree
Karim Kentouche
Facility Name
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII (Presidio Papa Giovanni XXIII)
City
Bergamo
State/Province
Hubei
ZIP/Postal Code
24127
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site contact
Phone
39352678597
First Name & Middle Initial & Last Name & Degree
Anna Falanga
Facility Name
Kyushu University Hospital
City
Fukuoka-shi
State/Province
Fukuoka-Ken
ZIP/Postal Code
812-8582
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+81926411151
Email
ischii@pediatr.med.kyushu-u.ac.jp
First Name & Middle Initial & Last Name & Degree
Masataka Ishimura
Facility Name
Hyogo College of Medicine Hospital
City
Nishinomiya
State/Province
Hyogo
ZIP/Postal Code
663-8501
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+81798456111
Email
parasol@mua.biglobe.ne.jp
First Name & Middle Initial & Last Name & Degree
Satoshi Higasa
Facility Name
Medical Hospital,Tokyo Medical and Dental University
City
Bunkyo City
State/Province
Tokyo
ZIP/Postal Code
113-8519
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+81358035646
Email
mkajiwara.bldt@tmd.ac.jp
First Name & Middle Initial & Last Name & Degree
Michiko Kajiwara
Facility Name
Samodzielny Publiczny Dzieciecy Szpital Kliniczny
City
Warszawa
ZIP/Postal Code
02-091
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+48223179614
Email
Anna.klukowska@litewska.edu.pl
First Name & Middle Initial & Last Name & Degree
Anna Klukowska
Facility Name
Instytut Hematologii i Transfuzjologii
City
Warszawa
ZIP/Postal Code
02-776
Country
Poland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+482234961581
Email
jwindyga@ihit.waw.pl
First Name & Middle Initial & Last Name & Degree
Jerzy Windyga
Facility Name
Complejo Hospitalario Universitario A Coruña
City
A Coruña
State/Province
La Coruña
ZIP/Postal Code
15006
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site contact
Phone
+34 981 17 66 68
Email
ma.fernanda.lopez.fernandez@sergas.es
First Name & Middle Initial & Last Name & Degree
Maria Fernanda Lopez Fernandez
Facility Name
Hospital de Cruces
City
Barakaldo
State/Province
Vizcaya
ZIP/Postal Code
48903
Country
Spain
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+34946006089
Email
delorbebarreto2@osakidetza.eus
First Name & Middle Initial & Last Name & Degree
Rafael Andres Del Ombre Barreto
Facility Name
Inselspital -Universitaetsspital Bern
City
Bern
ZIP/Postal Code
3010
Country
Switzerland
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Contact
Phone
+41316329022
Email
johanna.kremer@insel.ch
First Name & Middle Initial & Last Name & Degree
Johanna Kremer Hovinga
Facility Name
University College London Hospitals
City
London
State/Province
Greater London
ZIP/Postal Code
NW12PG
Country
United Kingdom
Individual Site Status
Active, not recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
IPD Sharing Access Criteria
IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
IPD Sharing URL
https://vivli.org/ourmember/takeda/
Links:
URL
https://clinicaltrials.takeda.com/study-detail/609976821f1122001e30a776?idFilter=%5B%22TAK-755-3002%22%5D
Description
To obtain more information on the study, click here/on this link.
Learn more about this trial
A Study of TAK-755 in Participants With Congenital Thrombotic Thrombocytopenic Purpura
We'll reach out to this number within 24 hrs