An Open Label Study to Determine the Safety and Efficacy of Replacement Factor VIII Protein (Known as rFVIIIFc) in Previously Untreated Males With Severe Hemophilia A
An Open-Label, Multicenter Evaluation of the Safety and Efficacy of Recombinant Coagulation Factor VIII Fc Fusion Protein (rFVIIIFc; BIIB031) in the Prevention and Treatment of Bleeding in Previously Untreated Patients With Severe Hemophilia A
2 other identifiers
interventional
108
14 countries
71
Brief Summary
The primary objective of the study was to evaluate the safety of rFVIIIFc (BIIB031) in previously untreated participants (PUPs) with severe hemophilia A. The secondary objectives were to evaluate the efficacy of rFVIIIFc in the prevention and treatment of bleeding episodes in PUPs, to evaluate rFVIIIFc consumption for the prevention and treatment of bleeding episodes in PUPs, and to describe experience with the use of rFVIIIFc for immune tolerance induction (ITI) in participants with inhibitors.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Jan 2015
Longer than P75 for phase_3
71 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 29, 2014
CompletedFirst Posted
Study publicly available on registry
September 9, 2014
CompletedStudy Start
First participant enrolled
January 12, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 23, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
September 23, 2019
CompletedResults Posted
Study results publicly available
August 13, 2020
CompletedApril 11, 2022
March 1, 2022
4.7 years
August 29, 2014
July 28, 2020
March 15, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay
A positive/confirmed inhibitor result occurs when a participant has a value \>=0.6 BU/mL by central laboratory testing using Nijmegen-modified Bethesda assay, that is confirmed on re-testing of a separate sample collected \>=2 weeks after the initial sample. Confirmed inhibitor development was based on all participants who had reached \>=10 EDs and had \>=1 inhibitor test performed at or beyond this milestone or who had an inhibitor. Exposure day (ED) is a 24-hour period in which participant received \>=1 dose of rFVIIIFc injections. Participants who did not develop an inhibitor but reached the milestone number of EDs were included in the denominator during calculation of percentage. Additionally, any participant who developed an inhibitor following the initial rFVIIIFc administration was included in the numerator and denominator during calculation of percentage.
Up to 3 years
Secondary Outcomes (9)
Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])
Up to 3 years
Annualized Number of Spontaneous Joint Bleeding Episodes
Up to 3 years
Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale
Up to 3 years
Total Number of Exposure Days (EDs)
Up to 3 years
Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes
Up to 3 years
- +4 more secondary outcomes
Study Arms (1)
rFVIIIFc
EXPERIMENTALParticipants were to receive rFVIIIFc as follows- Prophylaxis regimen (PR): rFVIIIFc 25-80 international units per kilogram (IU/kg), at 3- to 5-day intervals until participant reached greater than or equal to (\>=) 50 exposure days (ED: 24-hour period in which \>=1 injection/dose of rFVIIIFc was given), or study withdrawal/end of study. Adjustments to dose/dosing interval was done as needed by investigator; Treatment with an optional ER (Episodic regimen) can be initiated before PR at investigators discretion; ITI: rFVIIIFc 200 IU/kg, daily for participants who, after exposure to rFVIIIFc, had positive high titer inhibitor (\>=5.00 Bethesda Units per milliliter \[BU/mL\]) or positive low titer inhibitor (\>=0.60 and \<5.00 BU/mL) and had poorly controlled bleeding despite increased rFVIIIFc doses, or required bypassing agent to treat bleeding.
Interventions
Administered as specified in arm description
Eligibility Criteria
You may qualify if:
- Ability of the participant's legally authorized representative (e.g. their parent or legal guardian) to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use confidential health information in accordance with national and local participant privacy regulations.
- Weight \>=3.5 kg at the time of screening.
- Severe hemophilia A defined as less than (\<) 1 IU/dL (\<1%) endogenous FVIII documented in the medical record or as tested during the Screening Period.
You may not qualify if:
- Any exposure to blood components, factor VIII replacement products, including commercially available rFVIIIFc at any time prior to or during screening.
- History of positive inhibitor testing. A prior history of inhibitors was defined based on a patient's historical positive inhibitor test using the local laboratory Bethesda value for a positive inhibitor test (ie, equal to or above lower level of detection).
- History of hypersensitivity reactions associated with any rFVIIIFc administration.
- Other coagulation disorder(s) in addition to hemophilia A.
- Any concurrent clinically significant major disease that, in the opinion of the Investigator, would make the participant unsuitable for enrollment.
- Current systemic treatment with chemotherapy and/or other immunosuppressant drugs.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Bioverativ, a Sanofi companylead
- Swedish Orphan Biovitrumcollaborator
Study Sites (71)
Research Site
Little Rock, Arkansas, 72202, United States
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Duarte, California, 91010, United States
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Sacramento, California, 95817, United States
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San Francisco, California, 94143, United States
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Torrance, California, 90509, United States
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Indianapolis, Indiana, 46260, United States
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Louisville, Kentucky, 40202, United States
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Brewer, Maine, 04412, United States
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East Lansing, Michigan, 48823, United States
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Minneapolis, Minnesota, 55404, United States
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St Louis, Missouri, 63104, United States
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Buffalo, New York, 14209, United States
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New York, New York, 10065, United States
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Rochester, New York, 14621, United States
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Columbus, Ohio, 43205, United States
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Portland, Oregon, 97239, United States
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Philadelphia, Pennsylvania, 19104, United States
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Dallas, Texas, 75230, United States
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Dallas, Texas, 75235, United States
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Milwaukee, Wisconsin, 53226, United States
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Brisbane, 4029, Australia
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Parkville, 3052, Australia
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Perth, 6008, Australia
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Westmead, 2145, Australia
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Campinas, 13083-878, Brazil
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Canoas, 92425-900, Brazil
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Ribeirão Preto, 14048-900, Brazil
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Rio de Janeiro, 20211-030, Brazil
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São Paulo, 01227-200, Brazil
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Hamilton, L8S 4K1, Canada
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London, N6A 4G5, Canada
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Toronto, M5G 1X8, Canada
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Caen, 14033, France
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Le Kremlin-Bicêtre, 94270, France
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Lille, 59037, France
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Nantes, 44093, France
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Strasbourg, 67200, France
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Toulouse, 31059, France
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Tours, 37044, France
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Berlin, 13353, Germany
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Bonn, 53127, Germany
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Düsseldorf, 40225, Germany
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Frankfurt, 60590, Germany
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Hannover, 30625, Germany
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Dublin, D12 N512, Ireland
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Vicenza, VI, 36100, Italy
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Bari, 70123, Italy
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Florence, 50134, Italy
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Genova, 16148, Italy
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Milan, 20122, Italy
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Napoli, 80123, Italy
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Padua, 35128, Italy
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Rome, 161, Italy
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Rome, 165, Italy
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Leiden, 2333 ZA, Netherlands
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Utrecht, 3584 CX, Netherlands
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Auckland, 1023, New Zealand
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Christchurch, 8011, New Zealand
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Gdansk, 80-952, Poland
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Krakow, 30-663, Poland
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Lublin, 20-093, Poland
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Warsaw, 02-091, Poland
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Barcelona, 08035, Spain
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Madrid, 28046, Spain
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Stockholm, 171 76, Sweden
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Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom
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Basingstoke, Hampshire, RG24 9NA, United Kingdom
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Whitechapel, London, E1 1BB, United Kingdom
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Cardiff, CF14 4XW, United Kingdom
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London, WC1N3JH, United Kingdom
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Sheffield, S10 2TH, United Kingdom
Related Publications (2)
Carcao M, Schiavulli M, Kulkarni R, Rendo P, Foster M, Santagostino E, Casiano S, Konigs C. A post hoc analysis of previously untreated patients with severe hemophilia A who developed inhibitors in the PUPs A-LONG trial. Blood Adv. 2024 Mar 26;8(6):1494-1503. doi: 10.1182/bloodadvances.2023011475.
PMID: 38266154DERIVEDKonigs C, Ozelo MC, Dunn A, Kulkarni R, Nolan B, Brown SA, Schiavulli M, Gunawardena S, Mukhopadhyay S, Jayawardene D, Winding B, Carcao M. First study of extended half-life rFVIIIFc in previously untreated patients with hemophilia A: PUPs A-LONG final results. Blood. 2022 Jun 30;139(26):3699-3707. doi: 10.1182/blood.2021013563.
PMID: 35421219DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Trial Transparency Team
- Organization
- Bioverativ, a Sanofi company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 29, 2014
First Posted
September 9, 2014
Study Start
January 12, 2015
Primary Completion
September 23, 2019
Study Completion
September 23, 2019
Last Updated
April 11, 2022
Results First Posted
August 13, 2020
Record last verified: 2022-03
Data Sharing
- IPD Sharing
- Will share
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org