Clinical trial NCT02234323: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Keywords: prophylaxis treatment
Hemophilia A
Hemophilia
episodic treatment
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Swedish Orphan Biovitrum
First posted: 2014-09-09
Enrollment: 108
Sex: MALE
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Key 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.

Key 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.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With Confirmed Inhibitor Development as Measured by the Nijmegen-Modified Bethesda Assay
timeFrame: Up to 3 years
Secondary outcomes:
measure: Annualized Number of Bleeding Episodes (Spontaneous and Traumatic) Per Participant (Annualized Bleeding Rate [ABR])
timeFrame: Up to 3 years
measure: Annualized Number of Spontaneous Joint Bleeding Episodes
timeFrame: Up to 3 years
measure: Number of rFVIIIFc Injections With Excellent or Good, Moderate or None Treatment Response Assessed Using a 4-Point Scale
timeFrame: Up to 3 years
measure: Total Number of Exposure Days (EDs)
timeFrame: Up to 3 years
measure: Total Annualized rFVIIIFc Consumption Per Participant for the Prevention and Treatment of Bleeding Episodes
timeFrame: Up to 3 years
measure: Number of Injections of rFVIIIFc Required to Resolve a Bleeding Episode
timeFrame: Up to 3 years
measure: Average Dose Per Injection of rFVIIIFc Required to Resolve a Bleeding Episode
timeFrame: Up to 3 years
measure: Change From Baseline in rFVIIIFc Incremental Recovery (IR)
timeFrame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120
measure: Number of Participants With Response to Immune Tolerance Induction (ITI)
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Research Site
state: Arkansas
city: Duarte
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: San Francisco
country: United States
facility: Research Site
state: California
city: Torrance
country: United States
facility: Research Site
state: California
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Brewer
country: United States
facility: Research Site
state: Maine
city: East Lansing
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Buffalo
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Brisbane
country: Australia
facility: Research Site
city: Parkville
country: Australia
facility: Research Site
city: Perth
country: Australia
facility: Research Site
city: Westmead
country: Australia
facility: Research Site
city: Campinas
country: Brazil
facility: Research Site
city: Canoas
country: Brazil
facility: Research Site
city: Ribeirão Preto
country: Brazil
facility: Research Site
city: Rio de Janeiro
country: Brazil
facility: Research Site
city: São Paulo
country: Brazil
facility: Research Site
city: Hamilton
country: Canada
facility: Research Site
city: London
country: Canada
facility: Research Site
city: Toronto
country: Canada
facility: Research Site
city: Caen cedex 9
country: France
facility: Research Site
city: Le Kremlin Bicêtre cedex
country: France
facility: Research Site
city: Lille Cedex
country: France
facility: Research Site
city: Nantes Cedex 1
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Toulouse cedex
country: France
facility: Research Site
city: Tours cedex 9
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Bonn
country: Germany
facility: Research Site
city: Duesseldorf
country: Germany
facility: Research Site
city: Frankfurt
country: Germany
facility: Research Site
city: Hannöver
country: Germany
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
city: Vicenza
country: Italy
facility: Research Site
state: VI
city: Bari
country: Italy
facility: Research Site
city: Florence
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Milan
country: Italy
facility: Research Site
city: Napoli
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Rome
country: Italy
facility: Research Site
city: Leiden
country: Netherlands
facility: Research Site
city: Utrecht
country: Netherlands
facility: Research Site
city: Auckland
country: New Zealand
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
state: Cambridgeshire
city: Basingstoke
country: United Kingdom
facility: Research Site
state: Hampshire
city: Whitechapel
country: United Kingdom
facility: Research Site
state: London
city: Cardiff
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
Study officials:
References:
citation: 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.