Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Recombinant Coagulation Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Pediatric Subjects With Hemophilia A

NCT01458106 | Completed Phase 3 Results DMC

• 2 other identifiers: 8HA02PED2011-003073-28
• Study Type: interventional
• Target: 71
• Locations: 8 countries
• Sites: 23

Brief Summary

The primary objective of the study is to evaluate the safety of Recombinant Coagulation Factor VIII Fc Fusion Protein (rFVIIIFc) in previously treated pediatric subjects with hemophilia A. Secondary objectives of this study in this study population are as follows: to evaluate the efficacy of rFVIIIFc for prevention and treatment of bleeding episodes; to evaluate and assess the pharmacokinetics (PK) of rFVIIIFc; and to evaluate rFVIIIFc consumption for prevention and treatment of bleeding episodes.

Conditions

Hemophilia A

Outcome Measures

Primary Outcomes (1)

• Occurrence of FVIII Inhibitor Development

  An inhibitor test result ≥0.6 Bethesda units (BU)/mL, confirmed on 2 separate samples drawn 2 to 4 weeks apart, was considered positive. Both tests were to be performed by the central laboratory using the Nijmegen-modified Bethesda Assay. Incidences were summarized for any positive inhibitor for participants with ≥50 EDs to rFVIIIFc. In addition, the incidence for all participants, regardless of their EDs to rFVIIIFc, was also summarized. An exact 95% CI for the proportion of participants with a confirmed inhibitor was calculated using the Clopper-Pearson exact method for a binomial proportion.

  Up to Week 26 +/- 7 days, or up to 50 exposure days (EDs) if reached prior to Week 26

Secondary Outcomes (34)

• Annualized Bleeding Rate

  Up to Week 26 +/- 7 days (efficacy period as defined in description)

• Annualized Joint Bleeding Rate (Spontaneous)

  Up to Week 26 +/- 7 days (efficacy period as defined in description)

• Participant Assessment of Response to Injections to Treat a Bleeding Episode

  Up to Week 26 +/- 7 days

• Physician's Global Assessment of the Participant's Response to His rFVIIIFc Regimen

  Up to Week 26 +/- 7 days

• Annualized rFVIIIFc Consumption Per Participant

  Up to Week 26 +/- 7 days (efficacy period as defined in description)

Study Arms (1)

All participants

EXPERIMENTAL

PK subgroup: After a Washout Period of ≥72 hours, at the Baseline Visit (28±7 days prior to Day 1), participants receive a single IV injection of prestudy FVIII over 5 (±2) minutes at a dose of 50 IU/kg, rounded up to the nearest 250 IU increment, for a PK assessment. Following a second Washout Period of ≥72 hours, participants receive a single IV injection of rFVIIIFc over 5 (±2) minutes at a dose of 50 IU/kg for PK assessment. The first prophylactic dose of rFVIIIFc is administered at a starting dose of 25 IU/kg IV injection on Day 1 and 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated. Non-PK subgroup: On Day 1, a first prophylactic dose of rFVIIIFc of 25 IU/kg IV injection is given, followed by a dose of 50 IU/kg on Day 4. Dose increases to a maximum of 80 IU/kg, and frequency of administration to a minimum interval of once every 2 days, are allowed as indicated.

Drug: BIIB031 (rFVIIIFc); Drug: FVIII (PK subgroup only)

Interventions

BIIB031 (rFVIIIFc) DRUG

Vials of rFVIIIFc were combined as needed, based on the actual labeled potency to achieve the participant's calculated dose. Partial vial use was allowed, in order to achieve the calculated dose.

Also known as: ELOCTATE, efmoroctocog alfa, antihemophilic factor (recombinant), Fc fusion protein, recombinant coagulation factor VIII Fc fusion protein

All participants

FVIII (PK subgroup only) DRUG

Baseline prestudy FVIII dosing in participants who enter the PK subgroup. Vials of prestudy FVIII were combined as needed, based on the nominal labeled potency (e.g., 250 IU, 500 IU, and 1000 IU), to achieve the participant's calculated dose.

All participants

Eligibility Criteria

• Age: Up to 11 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Severe hemophilia A defined as \<1 IU/dL (\<1%) endogenous FVIII
• Male \<12 years of age and weight ≥13 kg
• History of at least 50 documented prior exposure days to FVIII
• No current, or history of, inhibitor development to FVIII

You may not qualify if:

• Other coagulation disorders in addition to Hemophilia A
• History of anaphylaxis associated with any FVIII or IV immunoglobulin administration

Sponsors & Collaborators

• Bioverativ Therapeutics Inc.: lead
• Swedish Orphan Biovitrum: collaborator

Study Sites (23)

Research Site

Los Angeles, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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Aurora, Colorado, United States

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Chicago, Illinois, United States

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Indianapolis, Indiana, United States

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St Louis, Missouri, United States

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Las Vegas, Nevada, United States

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Cincinnati, Ohio, United States

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Columbus, Ohio, United States

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Portland, Oregon, United States

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Pittsburgh, Pennsylvania, United States

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Brisbane, Queensland, Australia

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Melbourne, Victoria, Australia

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Hong Kong, Hong Kong

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Dublin, Ireland

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Groningen, Netherlands

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Lublin, Poland

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Johannesburg, South Africa

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Cambridge, Cambridgshire, United Kingdom

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Basingstoke, Hampshire, United Kingdom

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Glasgow, United Kingdom

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London, United Kingdom

Location

Related Publications (3)

• Raheja P, Kragh N, Bystricka L, Eriksson D, Aroui K, Mezghani M, Barbier S, Linari S. Long-term efmoroctocog alfa prophylaxis improves perceived pain, mental, and physical health in patients with hemophilia A: post hoc analysis of phase III trials using patient-reported outcomes. Ther Adv Hematol. 2024 Jul 30;15:20406207241257917. doi: 10.1177/20406207241257917. eCollection 2024.

  PMID: 39091324 DERIVED

• Katragadda S, Neelakantan S, Diao L, Wong N. Population Pharmacokinetic Analysis of Recombinant Factor VIII Fc Fusion Protein in Subjects With Severe Hemophilia A: Expanded to Include Pediatric Subjects. J Clin Pharmacol. 2021 Jul;61(7):889-900. doi: 10.1002/jcph.1854. Epub 2021 Apr 14.

  PMID: 33719084 DERIVED

• Young G, Mahlangu J, Kulkarni R, Nolan B, Liesner R, Pasi J, Barnes C, Neelakantan S, Gambino G, Cristiano LM, Pierce GF, Allen G. Recombinant factor VIII Fc fusion protein for the prevention and treatment of bleeding in children with severe hemophilia A. J Thromb Haemost. 2015 Jun;13(6):967-77. doi: 10.1111/jth.12911. Epub 2015 Apr 23.

  PMID: 25912075 DERIVED

MeSH Terms

Conditions

Hemophilia A

Interventions

factor VIII-Fc fusion protein

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Bioverativ Study Medical Director
• Organization: Bioverativ

clinicaltrials@bioverativ.com

Study Officials

• Medical Director

  Bioverativ Therapeutics Inc.

  STUDY DIRECTOR

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: October 20, 2011
• First Posted: October 24, 2011
• Study Start: November 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 19, 2020
• Results First Posted: December 12, 2014

Record last verified: 2018-08

Locations

HK (1); US (12); IE (1); AU (2); PL (1); GB (4); NL (1); ZA (1)