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BAX 855 Continuation

Primary Purpose

Hemophilia A

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

BAX855

About this trial

This is an interventional prevention trial for Hemophilia A

Eligibility Criteria

undefined - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

INCLUSION CRITERIA

Participants Transitioning from Other BAX 855 Studies:

Participants transitioning from other BAX 855 studies can be provided with the continuation study informed consent form (ICF) prior to the end of study visit to review and consider participation in this continuation study. These participants will complete any additional screening assessments within 2 weeks of the previous study's end of study visit and will return to the study site within 6 (± 1) weeks of the previous study end of study visit to confirm eligibility for this continuation study.

Participants transitioning from other BAX 855 studies who meet ALL of the following criteria are eligible for this study:
1. Participant has completed a previous BAX 855 study and is willing to immediately transition into this continuation study.
2. Participant is ≤75 years of age at screening of the previous BAX 855 study.
3. Participant continues to have a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged < 16 years) performance score of ≥ 60.
4. Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening.
5. Participant is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis.
6. If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
7. Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.
BAX 855 Naïve Participants:

BAX 855 naïve participants who are ≥ 12 years of age can only be enrolled in this continuation study after enrollment in the phase 2/3 pivotal study is closed. BAX 855 naïve participants who are < 12 years of age can only be enrolled in this continuation study after enrollment in the pediatric previously treated patient (PTP) study is closed.

- Enrolment of BAX 855 naïve participants will only start once the sponsor has notified the study sites accordingly.

BAX 855 naïve participants who meet ALL of the following criteria are eligible for this study:

Participant is ≤75 years of age at screening.
Participant is naïve to BAX 855.
Participant has severe hemophilia A (FVIII clotting activity < 1%) as confirmed by central laboratory at screening after at least a 72-hour washout period.
Participant aged ≥ 6 years has documented previous treatment with plasma-derived FVIII or rFVIII for ≥ 150 exposure days (EDs).
Participant aged < 6 years has documented previous treatment with plasma-derived FVIII concentrates or rFVIII for ≥ 50 EDs.
Participant is currently receiving prophylaxis or on-demand therapy with FVIII.
Participant has a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged < 16 years) performance score of ≥ 60.
Participant is HIV-; or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening.
Participant is HCV- by antibody or PCR testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis.
If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study.
Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol.

EXCLUSION CRITERA

- Participants Transitioning from Other BAX 855 Studies:

Participants transitioning from other BAX 855 studies who meet ANY of the following criteria are not eligible for this study:

Participant had detectable factor VIII (FVIII) inhibitory antibodies (≥ 0.6 Bethesda unit (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
Participant has developed FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay as determined at central laboratory in a previous BAX 855 study).
Participant has acquired a hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease) in a previous BAX 855 study.
Participant has severe chronic hepatic dysfunction (eg, ≥ 5 times upper limit of normal alanine aminotransferase [ALT], as confirmed by central laboratory at screening).
Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry.
Participant is scheduled to use other PEGylated drugs during study participation.
Participant is planning to take part in any other clinical study during the course of the continuation study, with the exception of any other parallel BAX 855 study.
Participant has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
Participant is a family member or employee of the investigator.
- BAX 855 Naïve Participants:

BAX 855 naïve participants who meet ANY of the following criteria are not eligible for this study:

Participant has detectable FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening.
Participant has history of FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay or the Bethesda assay) at any time prior to screening.
Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease).
Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG), or Tween 80.
Participant has severe chronic hepatic dysfunction eg, ≥ 5 times upper limit of normal ALT, as confirmed by central laboratory at screening).
Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening.
Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry.
Participant has current or recent (< 30 days) use of other PEGylated drugs prior to study participation or scheduled use of such drugs during study participation.
Participant has participated in another clinical study involving an IP other than BAX 855 or device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product (IP) or investigational device during the course of this study.
Participant has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance.
Participant is a family member or employee of the investigator.

Sites / Locations

Phoenix Childrens Hospital
University of Colorado
University of Florida College of Medicine
Ann & Robert H. Lurie Children's Hospital of Chicago
Bleeding and Clotting Disorders Institute
University of Kentucky Medical Center
University of Louisville
Tulane University School of Medicine
Children's Mercy Hospitals & Clinics
North Shore-Long Island Jewish Health System
New York - Presbyterian/Weill Cornell Medical Center
University of North Carolina at Chapel Hill
Duke University Medical Center
Cincinnati Children's Hospital Medical Center
Cleveland Clinic Foundation
Nationwide Children's Hospital
University of Oklahoma
Penn State Hershey Cancer Center
Palmetto Health Richland
University of Utah
Puget Sound Blood Group
Royal Adelaide Hospital
The Alfred Hospital
Fremantle Hospital
Landes-Frauen-und Kinderklinik Linz
Universitatsklinik fur Innere Medizin I
UMHAT "Sv. Georgi", EAD
SHAT of Oncohaematology Diseases
MHAT 'Sv. Marina', EAD
Fakultni nemocnice Brno
Fakultni nemocnice Olomouc
Fakultni nemocnice v Motole
Werlhof-Institut GmbH
Gerinnungszentrum Rhein-Ruhr
Vivantes Klinikum im Friedrichshain - Landsberger Allee
Universitaetsklinikum Hamburg-Eppendorf
Prince of Wales Hospital
Rambam Health Care Campus
Chaim Sheba Medical Center
Nagoya University Hospital
University of Occupational and Environmental Health Hospital
Hiroshima University Hospital
St. Marianna University School of Medicine Hospital
Nara Medical University Hospital
Tokyo Medical University Hospital
Ogikubo Hospital
Chonnam National University Hwasun Hospital
Pusan National University Hospital
Eulji University Hospital
Kyung Hee University Hospital at Gangdong
Ulsan University Hospital
Vilnius University Hospital Santariskiu Clinics, Public Institution
Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos
Penang General Hospital
Hospital Umum Sarawak
Hospital Sibu
Hospital Ampang
Pusat Darah Negara
Hospital Pulau Pinang
Academisch Medisch Centrum
Uniwersyteckie Centrum Kliniczne
Wojewodzki Szpital Specjalistyczny im.M.Kopernika w Lodzi
Sanador SRL
LLC "Alba Dent"
Regional Clinical Hospital
Hospital Universitari Son Espases
Complejo Hospitalario Universitario A Coruña
Hospital Regional Universitario de Malaga
Hospital Universitario La Paz
Hospital Universitari i Politecnic La Fe
Sjukhusapoteket Malmo
Karolinska
Universitaetsspital Zuerich
Taichung Veterans General Hospital
Tri-Service General Hospital
Ankara University Medical Faculty
Akdeniz University Faculty of Medicine
Istanbul University Cerrahpasa Medical Faculty
SI V.K.Gusak Emergency and Reconstructive Surgery Institute of NAMSU
SI Institute of Blood Pathology and Transfusion Medicine of NAMSU
Bristol Royal Hospital for Children
St Thomas' Hospital
Royal Free Hospital
Great Ormond Street Hospital for Children
Royal Manchester Children's Hospital
Southampton General Hospital
Leicester Royal Infirmary
Birmingham Children's Hospital
The Churchill Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Fixed BAX855 prophylaxis

Pharmacokinetic (PK)-tailored BAX 855 prophylaxis

Arm Description

45-80 IU/kg twice weekly to once per week.

PK-tailored prophylactic BAX855 regimen based on participant's individual PK profile to maintain a Factor VIII (FVIII) trough level

Outcomes

Primary Outcome Measures

Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)

Inhibitory antibodies to Factor VIII were measured by the Nijmegen modification of the Bethesda assay. Inhibitors had to be confirmed by 2 separate assessments within a 2 to 4 week period from the central laboratory.

Annualized Bleed Rate (ABR) - Spontaneous Bleeds

The ABR was assessed based upon each individual bleeding episode. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. The ABR of spontaneous bleeds was reported separately for twice weekly, PK-t R, each of the every 5 days and every 7 days treatment regimens at the time of bleed.

Secondary Outcome Measures

Total Annualized Bleed Rate (ABR)

The ABR was assessed based upon each individual bleeding episode. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. Bleeding occurring at multiple locations related to the same injury (e.g., knee and ankle bleed following a fall) was counted as a single bleeding episode. Total annualized bleed rate (spontaneous and traumatic bleeding episodes) was reported.

Overall Hemostatic Efficacy Rating of BAX 855 for Treatment of Breakthrough Bleeding Episodes

The participant or caregiver rated the overall treatment response at 24 (+/- 2) hours after the initiation of treatment using a 4-point efficacy rating scale as Excellent: Full relief of pain and cessation of objective signs of bleeding after a single infusion and no additional infusion is required for the control of bleeding; Good: Definite pain relief and/or improvement in signs of bleeding after a single infusion and possibly requires more than 1 infusion for complete resolution; Fair: Slight relief of pain and slight improvement in signs of bleeding after a single infusion and required more than 1 infusion for complete resolution and None: No improvement or condition worsens.

BAX 855 Infusions Needed to Treat Bleeding Episodes

The BAX 855 infusions to treat each bleeding episode was determined by the participant, the participant's caregiver, and/or investigator, and was based upon the participant's response to treatment. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII.

Total Time Intervals Between Bleeding Episodes

The time interval between bleeding episodes was calculated based upon the date and time reported for each bleeding episode. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII.

Average Dose of BAX 855 Per Prophylactic Infusion

The average dose of BAX 855 per prophylactic infusion was reported.

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE was any unfavorable and unintended sign (eg, an abnormal laboratory finding), symptom (eg, rash, pain, discomfort, fever, dizziness, etc.), disease (eg, peritonitis, bacteremia, etc.), or outcome of death temporally associated with the use of an investigational product (IP), whether or not considered causally related to the IP. A serious adverse event (SAE) was defined as an untoward medical occurrence that at any dose met one or more of the following criteria: outcome was fatal/resulted in death; was life-threatening; required inpatient hospitalization or resulted in prolongation of an existing hospitalization; resulted in persistent or significant disability/incapacity; was a congenital anomaly/birth defect; was a medically important event.

Change From Baseline in Body Temperature

Change in body temperature at pre-infusion and post-infusion at end of the study was reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling.

Change From Baseline in Pulse Rate

Change in pulse rate at pre-infusion and post-infusion at end of the study was reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling.

Change From Baseline in Respiratory Rate

Change in respiratory rate at pre-infusion and post-infusion at end of the study was reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling.

Change From Baseline in Blood Pressure

Change in systolic and diastolic blood pressure at pre-infusion and post-infusion at end of the study were reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling, SBP refers to systolic blood pressure, DBP refers to diastolic blood pressure.

Number of Participants With Shifts in Clinical Chemistry Laboratory Assessments.

The number of participants with clinically significant shifts from "normal" "abnormal clinically significant (CS)" and "abnormal not clinically significant (abnormal NCS)" at baseline to "normal" "abnormal clinically significant (CS) and abnormal clinically significant (NCS)" at completion were reported. In the below table, FDR refers to fixed dose regimen at the time of sampling, AlA refers to alanine aminotransferase, AP refers to alkaline phosphatase, AsA refers to aspartate aminotransferase.

Number of Participants With Shifts in Hematology Laboratory Assessments

The number of participants with clinically significant shifts from "normal" "abnormal clinically significant (CS)" and "abnormal not clinically significant (abnormal NCS)" at baseline to "normal" "abnormal clinically significant (CS) and abnormal clinically significant (NCS)" at completion were reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling, Leu refers to leukocytes, MCV refers to mean corpuscular volume, Lym/Leu refers to lymphocytes/leukocytes.

Number of Participants With Shifts in Lipid Panel Assessments

The number of participants with clinically significant shifts from "normal" "abnormal clinically significant (CS)" and "abnormal not clinically significant (abnormal NCS)" at baseline to "normal" "abnormal clinically significant (CS) and abnormal clinically significant (NCS)" at completion were reported.. In the below table, HDL refers to high density lipoprotein, LDL refers to low density lipoprotein, VLDL refers to very low density lipoprotein.

Number of Participants With Binding Antibodies

Binding antibodies (IgG and IgM) against FVIII, polyethylene glycol (PEG) and PEGylated FVIII (PEG-FVIII) were analyzed using enzyme-linked immunosorbent assay (ELISA).

Number of Participants With Anti-Chinese Hamster Ovary (CHO) Antibodies

Testing for binding of anti-CHO protein antibodies was performed on citrate-anti-coagulated plasma using an ELISA employing polyclonal antihuman IgG antibodies.

Change From Baseline in Bleed Severity

Hemophilia symptom (haemo-SYM) questionnaire has two subscales: pain and bleed. It was used to asses the bleed severity for participants >=18 years of age as: severity of spontaneous bleeding in my joints (unrelated to injury or activity), spontaneous bleeding in my muscles (unrelated to injury or activity), prolonged bleeding after injury in spite of treatment, intense pain because of bleeding event, joint pain due to active bleed and bleeding during personal hygiene routine, blood in my urine, nose bleeds and assigned a score of 0=Absent, 1=very mild, 2=mild, 3=moderate, 4=severe and 5=very severe. The score was determined as (mean score/5)*100 where mean score is the mean of the available results in the particular subscale. Higher scores on the Haemo-SYM indicate more severe symptoms. Therefore, negative change scores indicate that symptoms have improved. Here 'n' refers to the number of participants evaluable for this endpoint.

Change From Baseline in Pain Severity

Hemophilia symptom (haemo-SYM) questionnaire has two subscales: pain and bleed. It was used to asses the pain severity for participants >=18 years of age as: pain because of swelling in my joints, climbing stairs, upon waking in the morning, active arthritis; constant pain, in my muscles, that needs medication; joint sensitivity to weather conditions; reduced range of joint movement, joint deformity, sleep disturbance because of pain or bleeds, blood in my urine, nose bleeds and assigned a score of 0=Absent, 1=very mild, 2=mild, 3=moderate, 4=severe and 5=very severe. The score was determined as (mean score/5)*100 where mean score is the mean of the available results in the particular subscale. Higher scores on the Haemo-SYM indicate more severe symptoms. Therefore, negative change scores indicate that symptoms have improved. Here 'n' refers to the number of participants evaluable for this endpoint.

Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Short Form-36 (SF-36)

HRQoL in participants aged >=14 years was measured using the SF-36 questionnaire. The questionnaire was divided into 8 domains and scored as: physical functioning (1=yes, limited a lot to 3=no, not limited at all), role-physical (1=all of the time to 5=none of the time), bodily pain (1=very severe to 6=none), general health (1=poor to 5=excellent), vitality (1=none of the time to 5=all of the time), social functioning (1=all of the time: to 5=none of the time), role emotional (1=all of the time to 5=none of the time) and mental health (1=all of the time to 5=none of the time). The score for each domain is then to be transformed to a 0-100 range as [(actual raw score-lowest possible raw score)/possible raw score range]*100. Positive change scores indicate improved HRQoL. in the below table 'FDR' indicates fixed dose regimen, 'PK-tr' indicates pharmacokinetically tailored regimen and 'n' refers to the number of participants evaluable for this endpoint.

Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Pediatrics Quality of Life (PedsQL) Questionnaire

HRQoL in participants aged <14 years was measured using the PedsQL. It capture data for the following domains: physical functioning, emotional functioning, social functioning, school functioning, psychosocial functioning, physical health and a total score. Each question of the PedsQL was scored as Never: 100, almost never: 75, sometimes: 50, often: 25, almost always: 0. The mean of the individual question scores was calculated. Lower scores on the PedsQL indicating worse HRQoL. Here, FDR refers to fixed dose regimen, PK-t R refers to PK-tailored regimen. Here 'n' refers to the number of participants evaluable for this endpoint. Here 'n' refers to the number of participants evaluable for this endpoint.

Full Information

NCT ID

NCT01945593

First Posted

September 16, 2013

Last Updated

April 30, 2021

Sponsor

Baxalta now part of Shire

Collaborators

Baxalta Innovations GmbH, now part of Shire

1. Study Identification

Unique Protocol Identification Number

NCT01945593

Brief Title

BAX 855 Continuation

Official Title

A Phase 3b Continuation Study of the Safety and Efficacy of PEGylated Recombinant Factor VIII (PEG-rFVIII; BAX 855) in Prophylaxis of Bleeding in Previously Treated Patients With Severe Hemophilia A

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Completed

Study Start Date

October 15, 2013 (Actual)

Primary Completion Date

March 2, 2018 (Actual)

Study Completion Date

March 2, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Baxalta now part of Shire

Collaborators

Baxalta Innovations GmbH, now part of Shire

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

To continue the evaluation of the safety and efficacy of BAX 855 for prophylaxis and treatment of bleeding episodes in adult and pediatric previously treated patients (PTPs) aged ≤ 75 years of age with severe hemophilia A.

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

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

218 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Fixed BAX855 prophylaxis

Arm Type

Experimental

Arm Description

45-80 IU/kg twice weekly to once per week.

Arm Title

Pharmacokinetic (PK)-tailored BAX 855 prophylaxis

Arm Type

Experimental

Arm Description

PK-tailored prophylactic BAX855 regimen based on participant's individual PK profile to maintain a Factor VIII (FVIII) trough level

Intervention Type

Biological

Intervention Name(s)

BAX855

Other Intervention Name(s)

ADYNOVATE, BAX 855, PEGylated Recombinant Factor VIII

Intervention Description

Antihemophilic Factor (Recombinant), PEGylated

Primary Outcome Measure Information:

Title

Number of Participants With Inhibitory Antibodies to Factor VIII (FVIII)

Description

Time Frame

Baseline through end of study (53 months)

Title

Annualized Bleed Rate (ABR) - Spontaneous Bleeds

Description

Time Frame

Baseline through end of study (53 months)

Secondary Outcome Measure Information:

Title

Total Annualized Bleed Rate (ABR)

Description

The ABR was assessed based upon each individual bleeding episode. A bleeding episode was defined as subjective (pain consistent with a joint bleed) or objective evidence of bleeding which may or may not require treatment with FVIII. Bleeding occurring at multiple locations related to the same injury (e.g., knee and ankle bleed following a fall) was counted as a single bleeding episode. Total annualized bleed rate (spontaneous and traumatic bleeding episodes) was reported.

Time Frame

Baseline through end of study (53 months)

Title

Overall Hemostatic Efficacy Rating of BAX 855 for Treatment of Breakthrough Bleeding Episodes

Description

Time Frame

Baseline through end of study (53 months)

Title

BAX 855 Infusions Needed to Treat Bleeding Episodes

Description

Time Frame

Baseline through end of study (53 months)

Title

Total Time Intervals Between Bleeding Episodes

Description

Time Frame

Baseline through end of study (53 months)

Title

Average Dose of BAX 855 Per Prophylactic Infusion

Description

The average dose of BAX 855 per prophylactic infusion was reported.

Time Frame

Baseline through end of study (53 months)

Title

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

Description

Time Frame

Baseline through end of study (53 months)

Title

Change From Baseline in Body Temperature

Description

Time Frame

Baseline, end of study (53 months)

Title

Change From Baseline in Pulse Rate

Description

Time Frame

Baseline, end of study (53 months)

Title

Change From Baseline in Respiratory Rate

Description

Time Frame

Baseline, end of study (53 months)

Title

Change From Baseline in Blood Pressure

Description

Time Frame

Baseline, end of study (53 months)

Title

Number of Participants With Shifts in Clinical Chemistry Laboratory Assessments.

Description

Time Frame

Baseline through end of study (53 months)

Title

Number of Participants With Shifts in Hematology Laboratory Assessments

Description

The number of participants with clinically significant shifts from "normal" "abnormal clinically significant (CS)" and "abnormal not clinically significant (abnormal NCS)" at baseline to "normal" "abnormal clinically significant (CS) and abnormal clinically significant (NCS)" at completion were reported. In the below table, FDR refers to fixed dose regimen, PK-tR refers to PK tailored regimen at the time of sampling, Leu refers to leukocytes, MCV refers to mean corpuscular volume, Lym/Leu refers to lymphocytes/leukocytes.

Time Frame

Baseline through end of study (53 months)

Title

Number of Participants With Shifts in Lipid Panel Assessments

Description

The number of participants with clinically significant shifts from "normal" "abnormal clinically significant (CS)" and "abnormal not clinically significant (abnormal NCS)" at baseline to "normal" "abnormal clinically significant (CS) and abnormal clinically significant (NCS)" at completion were reported.. In the below table, HDL refers to high density lipoprotein, LDL refers to low density lipoprotein, VLDL refers to very low density lipoprotein.

Time Frame

Baseline through end of study (53 months)

Title

Number of Participants With Binding Antibodies

Description

Binding antibodies (IgG and IgM) against FVIII, polyethylene glycol (PEG) and PEGylated FVIII (PEG-FVIII) were analyzed using enzyme-linked immunosorbent assay (ELISA).

Time Frame

Baseline through end of study (53 months)

Title

Number of Participants With Anti-Chinese Hamster Ovary (CHO) Antibodies

Description

Testing for binding of anti-CHO protein antibodies was performed on citrate-anti-coagulated plasma using an ELISA employing polyclonal antihuman IgG antibodies.

Time Frame

Baseline through end of study (53 months)

Title

Change From Baseline in Bleed Severity

Description

Time Frame

Baseline, end of study (53 months)

Title

Change From Baseline in Pain Severity

Description

Time Frame

Baseline, end of study (53 months)

Title

Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Short Form-36 (SF-36)

Description

Time Frame

Baseline, end of study (53 months)

Title

Change From Baseline in Patient Reported Outcomes: Health-related Quality of Life (HRQoL): Pediatrics Quality of Life (PedsQL) Questionnaire

Description

Time Frame

Baseline, end of study (53 months)

10. Eligibility

Sex

All

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

INCLUSION CRITERIA Participants Transitioning from Other BAX 855 Studies: Participants transitioning from other BAX 855 studies can be provided with the continuation study informed consent form (ICF) prior to the end of study visit to review and consider participation in this continuation study. These participants will complete any additional screening assessments within 2 weeks of the previous study's end of study visit and will return to the study site within 6 (± 1) weeks of the previous study end of study visit to confirm eligibility for this continuation study. Participants transitioning from other BAX 855 studies who meet ALL of the following criteria are eligible for this study: Participant has completed a previous BAX 855 study and is willing to immediately transition into this continuation study. Participant is ≤75 years of age at screening of the previous BAX 855 study. Participant continues to have a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged < 16 years) performance score of ≥ 60. Participant is human immunodeficiency virus negative (HIV-); or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening. Participant is hepatitis C virus negative (HCV-) by antibody or polymerase chain reaction (PCR) testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis. If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study. Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol. BAX 855 Naïve Participants: BAX 855 naïve participants who are ≥ 12 years of age can only be enrolled in this continuation study after enrollment in the phase 2/3 pivotal study is closed. BAX 855 naïve participants who are < 12 years of age can only be enrolled in this continuation study after enrollment in the pediatric previously treated patient (PTP) study is closed. - Enrolment of BAX 855 naïve participants will only start once the sponsor has notified the study sites accordingly. BAX 855 naïve participants who meet ALL of the following criteria are eligible for this study: Participant is ≤75 years of age at screening. Participant is naïve to BAX 855. Participant has severe hemophilia A (FVIII clotting activity < 1%) as confirmed by central laboratory at screening after at least a 72-hour washout period. Participant aged ≥ 6 years has documented previous treatment with plasma-derived FVIII or rFVIII for ≥ 150 exposure days (EDs). Participant aged < 6 years has documented previous treatment with plasma-derived FVIII concentrates or rFVIII for ≥ 50 EDs. Participant is currently receiving prophylaxis or on-demand therapy with FVIII. Participant has a Karnofsky (for participants aged ≥ 16 years) or Lansky (for participants aged < 16 years) performance score of ≥ 60. Participant is HIV-; or HIV+ with stable disease and CD4+ count ≥ 200 cells/mm^3, as confirmed by central laboratory at screening. Participant is HCV- by antibody or PCR testing (if positive, antibody titer will be confirmed by PCR), as confirmed by central laboratory at screening; or HCV+ with chronic stable hepatitis. If female of childbearing potential, participant presents with a negative urine pregnancy test and agrees to employ adequate birth control measures for the duration of the study. Participant and/or legally authorized representative is willing and able to comply with the requirements of the protocol. EXCLUSION CRITERA - Participants Transitioning from Other BAX 855 Studies: Participants transitioning from other BAX 855 studies who meet ANY of the following criteria are not eligible for this study: Participant had detectable factor VIII (FVIII) inhibitory antibodies (≥ 0.6 Bethesda unit (BU) using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening. Participant has developed FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay as determined at central laboratory in a previous BAX 855 study). Participant has acquired a hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease) in a previous BAX 855 study. Participant has severe chronic hepatic dysfunction (eg, ≥ 5 times upper limit of normal alanine aminotransferase [ALT], as confirmed by central laboratory at screening). Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening. Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry. Participant is scheduled to use other PEGylated drugs during study participation. Participant is planning to take part in any other clinical study during the course of the continuation study, with the exception of any other parallel BAX 855 study. Participant has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance. Participant is a family member or employee of the investigator. BAX 855 Naïve Participants: BAX 855 naïve participants who meet ANY of the following criteria are not eligible for this study: Participant has detectable FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay) as confirmed by central laboratory at screening. Participant has history of FVIII inhibitory antibodies (≥ 0.6 BU using the Nijmegen modification of the Bethesda assay or the Bethesda assay) at any time prior to screening. Participant has been diagnosed with an inherited or acquired hemostatic defect other than hemophilia A (eg, qualitative platelet defect or von Willebrand's disease). Participant has known hypersensitivity towards mouse or hamster proteins, polyethylene glycol (PEG), or Tween 80. Participant has severe chronic hepatic dysfunction eg, ≥ 5 times upper limit of normal ALT, as confirmed by central laboratory at screening). Participant has severe renal impairment (serum creatinine > 2.0 mg/dL), as confirmed by central laboratory at screening. Participant experienced a life-threatening or gastrointestinal bleeding episode within 3 months prior to study entry. Participant has current or recent (< 30 days) use of other PEGylated drugs prior to study participation or scheduled use of such drugs during study participation. Participant has participated in another clinical study involving an IP other than BAX 855 or device within 30 days prior to enrollment or is scheduled to participate in another clinical study involving an investigational product (IP) or investigational device during the course of this study. Participant has medical, psychiatric, or cognitive illness or recreational drug/alcohol use that, in the opinion of the investigator, would affect participant safety or compliance. Participant is a family member or employee of the investigator.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Study Director

Organizational Affiliation

Takeda

Official's Role

Study Director

Facility Information:

Facility Name

Phoenix Childrens Hospital

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85016-7710

Country

United States

Facility Name

University of Colorado

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Facility Name

University of Florida College of Medicine

City

Gainesville

State/Province

Florida

ZIP/Postal Code

32610-0278

Country

United States

Facility Name

Ann & Robert H. Lurie Children's Hospital of Chicago

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611-2605

Country

United States

Facility Name

Bleeding and Clotting Disorders Institute

City

Peoria

State/Province

Illinois

ZIP/Postal Code

61614

Country

United States

Facility Name

University of Kentucky Medical Center

City

Lexington

State/Province

Kentucky

ZIP/Postal Code

40536-0284

Country

United States

Facility Name

University of Louisville

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Tulane University School of Medicine

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70112

Country

United States

Facility Name

Children's Mercy Hospitals & Clinics

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64108

Country

United States

Facility Name

North Shore-Long Island Jewish Health System

City

New Hyde Park

State/Province

New York

ZIP/Postal Code

11040

Country

United States

Facility Name

New York - Presbyterian/Weill Cornell Medical Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

University of North Carolina at Chapel Hill

City

Chapel Hill

State/Province

North Carolina

ZIP/Postal Code

27599-7016

Country

United States

Facility Name

Duke University Medical Center

City

Durham

State/Province

North Carolina

ZIP/Postal Code

27705

Country

United States

Facility Name

Cincinnati Children's Hospital Medical Center

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45229

Country

United States

Facility Name

Cleveland Clinic Foundation

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

Nationwide Children's Hospital

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43205

Country

United States

Facility Name

University of Oklahoma

City

Oklahoma City

State/Province

Oklahoma

ZIP/Postal Code

73104

Country

United States

Facility Name

Penn State Hershey Cancer Center

City

Hershey

State/Province

Pennsylvania

ZIP/Postal Code

17033

Country

United States

Facility Name

Palmetto Health Richland

City

Columbia

State/Province

South Carolina

ZIP/Postal Code

29203-6863

Country

United States

Facility Name

University of Utah

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84108

Country

United States

Facility Name

Puget Sound Blood Group

City

Seattle

State/Province

Washington

ZIP/Postal Code

98104

Country

United States

Facility Name

Royal Adelaide Hospital

City

Adelaide

State/Province

South Australia

ZIP/Postal Code

5000

Country

Australia

Facility Name

The Alfred Hospital

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3004

Country

Australia

Facility Name

Fremantle Hospital

City

Fremantle

State/Province

Western Australia

ZIP/Postal Code

6160

Country

Australia

Facility Name

Landes-Frauen-und Kinderklinik Linz

City

Linz

ZIP/Postal Code

4020

Country

Austria

Facility Name

Universitatsklinik fur Innere Medizin I

City

Vienna

ZIP/Postal Code

1090

Country

Austria

Facility Name

UMHAT "Sv. Georgi", EAD

City

Plovdiv

ZIP/Postal Code

4002

Country

Bulgaria

Facility Name

SHAT of Oncohaematology Diseases

City

Sofia

ZIP/Postal Code

1527

Country

Bulgaria

Facility Name

MHAT 'Sv. Marina', EAD

City

Varna

ZIP/Postal Code

9010

Country

Bulgaria

Facility Name

Fakultni nemocnice Brno

City

Brno

ZIP/Postal Code

625 00

Country

Czechia

Facility Name

Fakultni nemocnice Olomouc

City

Olomouc

ZIP/Postal Code

775 20

Country

Czechia

Facility Name

Fakultni nemocnice v Motole

City

Praha 5

ZIP/Postal Code

150 06

Country

Czechia

Facility Name

Werlhof-Institut GmbH

City

Hannover

State/Province

Niedersachsen

ZIP/Postal Code

30159

Country

Germany

Facility Name

Gerinnungszentrum Rhein-Ruhr

City

Duisburg

State/Province

Nordrhein Westfalen

ZIP/Postal Code

47051

Country

Germany

Facility Name

Vivantes Klinikum im Friedrichshain - Landsberger Allee

City

Berlin

ZIP/Postal Code

10249

Country

Germany

Facility Name

Universitaetsklinikum Hamburg-Eppendorf

City

Hamburg

ZIP/Postal Code

20246

Country

Germany

Facility Name

Prince of Wales Hospital

City

Shatin

ZIP/Postal Code

00000

Country

Hong Kong

Facility Name

Rambam Health Care Campus

City

Haifa

ZIP/Postal Code

3109601

Country

Israel

Facility Name

Chaim Sheba Medical Center

City

Ramat-Gan

ZIP/Postal Code

52621

Country

Israel

Facility Name

Nagoya University Hospital

City

Nagoya-shi

State/Province

Aichi-Ken

ZIP/Postal Code

466-8560

Country

Japan

Facility Name

University of Occupational and Environmental Health Hospital

City

Kitakyushu-shi

State/Province

Fukuoka-Ken

ZIP/Postal Code

807-8556

Country

Japan

Facility Name

Hiroshima University Hospital

City

Hiroshima-shi

State/Province

Hiroshima-Ken

ZIP/Postal Code

734-8551

Country

Japan

Facility Name

St. Marianna University School of Medicine Hospital

City

Kawasaki-shi

State/Province

Kanagawa-Ken

ZIP/Postal Code

216-8511

Country

Japan

Facility Name

Nara Medical University Hospital

City

Kashihara-shi

State/Province

Nara-Ken

ZIP/Postal Code

634-8522

Country

Japan

Facility Name

Tokyo Medical University Hospital

City

Shinjuku-ku

State/Province

Tokyo-To

ZIP/Postal Code

160-0023

Country

Japan

Facility Name

Ogikubo Hospital

City

Suginami City

State/Province

Tokyo

ZIP/Postal Code

167-8515

Country

Japan

Facility Name

Chonnam National University Hwasun Hospital

City

Hwasun-gun

State/Province

Jeollanam-do

ZIP/Postal Code

519-763

Country

Korea, Republic of

Facility Name

Pusan National University Hospital

City

Busan

ZIP/Postal Code

602-739

Country

Korea, Republic of

Facility Name

Eulji University Hospital

City

Daejeon

ZIP/Postal Code

302-799

Country

Korea, Republic of

Facility Name

Kyung Hee University Hospital at Gangdong

City

Seoul

ZIP/Postal Code

134-727

Country

Korea, Republic of

Facility Name

Ulsan University Hospital

City

Ulsan

ZIP/Postal Code

682-714

Country

Korea, Republic of

Facility Name

Vilnius University Hospital Santariskiu Clinics, Public Institution

City

Vilnius

ZIP/Postal Code

8661

Country

Lithuania

Facility Name

Children's Hospital, Affiliate of Vilnius University Hospital Santariskiu Klinikos

City

Vilnius

ZIP/Postal Code

LT-08406

Country

Lithuania

Facility Name

Penang General Hospital

City

George Town

State/Province

Penang

ZIP/Postal Code

10990

Country

Malaysia

Facility Name

Hospital Umum Sarawak

City

Kuching

State/Province

Sarawak

ZIP/Postal Code

93586

Country

Malaysia

Facility Name

Hospital Sibu

City

Sibu

State/Province

Sarawak

ZIP/Postal Code

96000

Country

Malaysia

Facility Name

Hospital Ampang

City

Ampang

State/Province

Selangor

ZIP/Postal Code

68000

Country

Malaysia

Facility Name

Pusat Darah Negara

City

Kuala Lumpur

ZIP/Postal Code

50400

Country

Malaysia

Facility Name

Hospital Pulau Pinang

City

Pulau Pinang

ZIP/Postal Code

10450

Country

Malaysia

Facility Name

Academisch Medisch Centrum

City

Amsterdam

ZIP/Postal Code

1105 AZ

Country

Netherlands

Facility Name

Uniwersyteckie Centrum Kliniczne

City

Gdansk

ZIP/Postal Code

80-952

Country

Poland

Facility Name

Wojewodzki Szpital Specjalistyczny im.M.Kopernika w Lodzi

City

Lodz

ZIP/Postal Code

93-510

Country

Poland

Facility Name

Sanador SRL

City

Bucuresti

ZIP/Postal Code

11038

Country

Romania

Facility Name

LLC "Alba Dent"

City

Kirov

ZIP/Postal Code

610000

Country

Russian Federation

Facility Name

Regional Clinical Hospital

City

Krasnoyarsk

ZIP/Postal Code

660022

Country

Russian Federation

Facility Name

Hospital Universitari Son Espases

City

Palma de Mallorca

State/Province

Baleares

ZIP/Postal Code

7010

Country

Spain

Facility Name

Complejo Hospitalario Universitario A Coruña

City

A Coruña

State/Province

La Coruña

ZIP/Postal Code

15006

Country

Spain

Facility Name

Hospital Regional Universitario de Malaga

City

Malaga

State/Province

Málaga

ZIP/Postal Code

29010

Country

Spain

Facility Name

Hospital Universitario La Paz

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Hospital Universitari i Politecnic La Fe

City

Valencia

ZIP/Postal Code

46026

Country

Spain

Facility Name

Sjukhusapoteket Malmo

City

Malmo

ZIP/Postal Code

21428

Country

Sweden

Facility Name

Karolinska

City

Stockholm

ZIP/Postal Code

17164

Country

Sweden

Facility Name

Universitaetsspital Zuerich

City

Zuerich

ZIP/Postal Code

8091

Country

Switzerland

Facility Name

Taichung Veterans General Hospital

City

Taichung

ZIP/Postal Code

40705

Country

Taiwan

Facility Name

Tri-Service General Hospital

City

Taipei

ZIP/Postal Code

11490

Country

Taiwan

Facility Name

Ankara University Medical Faculty

City

Ankara

ZIP/Postal Code

063100

Country

Turkey

Facility Name

Akdeniz University Faculty of Medicine

City

Antalya

ZIP/Postal Code

07059

Country

Turkey

Facility Name

Istanbul University Cerrahpasa Medical Faculty

City

Istanbul

ZIP/Postal Code

34098

Country

Turkey

Facility Name

SI V.K.Gusak Emergency and Reconstructive Surgery Institute of NAMSU

City

Donetsk

ZIP/Postal Code

83045

Country

Ukraine

Facility Name

SI Institute of Blood Pathology and Transfusion Medicine of NAMSU

City

Lviv

ZIP/Postal Code

79044

Country

Ukraine

Facility Name

Bristol Royal Hospital for Children

City

Bristol

State/Province

Avon

ZIP/Postal Code

BS2 8BJ

Country

United Kingdom

Facility Name

St Thomas' Hospital

City

London

State/Province

Greater London

ZIP/Postal Code

SE1 7EH

Country

United Kingdom

Facility Name

Royal Free Hospital

City

London

State/Province

Greater London

ZIP/Postal Code

WC1E 6AG

Country

United Kingdom

Facility Name

Great Ormond Street Hospital for Children

City

London

State/Province

Greater London

ZIP/Postal Code

WC1N 3JH

Country

United Kingdom

Facility Name

Royal Manchester Children's Hospital

City

Manchester

State/Province

Greater Manchester

ZIP/Postal Code

M13 9WL

Country

United Kingdom

Facility Name

Southampton General Hospital

City

Southampton

State/Province

Hampshire

ZIP/Postal Code

SO16 6YD

Country

United Kingdom

Facility Name

Leicester Royal Infirmary

City

Leicester

State/Province

Leicestershire

ZIP/Postal Code

LE1 5WW

Country

United Kingdom

Facility Name

Birmingham Children's Hospital

City

Birmingham

State/Province

West Midlands

ZIP/Postal Code

B4 6NH

Country

United Kingdom

Facility Name

The Churchill Hospital

City

Oxford

ZIP/Postal Code

OX3 7LE

Country

United Kingdom

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/

Learn more about this trial

BAX 855 Continuation

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