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

NCT ID: NCT02234323

Last Updated: 2022-04-11

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

108 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-01-12

Study Completion Date

2019-09-23

Brief Summary

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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.

Detailed Description

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Conditions

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Hemophilia A

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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rFVIIIFc

Participants 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.

Group Type EXPERIMENTAL

rFVIIIFc

Intervention Type BIOLOGICAL

Administered as specified in arm description

Interventions

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rFVIIIFc

Administered as specified in arm description

Intervention Type BIOLOGICAL

Other Intervention Names

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Eloctate; BIIB031; efmoroctocog alfa; recombinant coagulation factor VIII Fc fusion protein; antihemophilic factor [recombinant] Fc fusion protein

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Maximum Eligible Age

5 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Swedish Orphan Biovitrum

INDUSTRY

Sponsor Role collaborator

Bioverativ, a Sanofi company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Little Rock, Arkansas, United States

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Duarte, California, United States

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Sacramento, California, United States

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San Francisco, California, United States

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Torrance, California, United States

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Indianapolis, Indiana, United States

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Louisville, Kentucky, United States

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Brewer, Maine, United States

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East Lansing, Michigan, United States

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Minneapolis, Minnesota, United States

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St Louis, Missouri, United States

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Buffalo, New York, United States

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New York, New York, United States

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Rochester, New York, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Dallas, Texas, United States

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Dallas, Texas, United States

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Milwaukee, Wisconsin, United States

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Brisbane, , Australia

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Parkville, , Australia

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Perth, , Australia

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Westmead, , Australia

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Campinas, , Brazil

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Canoas, , Brazil

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Ribeirão Preto, , Brazil

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Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Hamilton, , Canada

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London, , Canada

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Toronto, , Canada

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Caen, , France

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Le Kremlin-Bicêtre, , France

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Lille, , France

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Nantes, , France

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Strasbourg, , France

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Toulouse, , France

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Tours, , France

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Berlin, , Germany

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Bonn, , Germany

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Düsseldorf, , Germany

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Frankfurt, , Germany

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Hannover, , Germany

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Dublin, , Ireland

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Vicenza, VI, Italy

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Bari, , Italy

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Florence, , Italy

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Genova, , Italy

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Milan, , Italy

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Napoli, , Italy

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Padua, , Italy

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Rome, , Italy

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Rome, , Italy

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Leiden, , Netherlands

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Utrecht, , Netherlands

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Auckland, , New Zealand

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Christchurch, , New Zealand

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Gdansk, , Poland

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Krakow, , Poland

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Lublin, , Poland

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Warsaw, , Poland

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Barcelona, , Spain

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Madrid, , Spain

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Stockholm, , Sweden

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Cambridge, Cambridgeshire, United Kingdom

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Basingstoke, Hampshire, United Kingdom

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Whitechapel, London, United Kingdom

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Cardiff, , United Kingdom

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London, , United Kingdom

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Sheffield, , United Kingdom

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Countries

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United States Australia Brazil Canada France Germany Ireland Italy Netherlands New Zealand Poland Spain Sweden United Kingdom

References

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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.

Reference Type DERIVED
PMID: 38266154 (View on PubMed)

Konigs 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.

Reference Type DERIVED
PMID: 35421219 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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2013-005512-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

997HA306

Identifier Type: -

Identifier Source: org_study_id

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