Study of Recombinant Coagulation Factor IX Fc Fusion Protein, BIIB029, in Previously Treated Pediatric Participants With Hemophilia B

NCT01440946 | Completed Phase 3 Results DMC

• 2 other identifiers: 9HB02PED2011-003076-36
• Study Type: interventional
• Target: 30
• Locations: 6 countries
• Sites: 15

Brief Summary

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

Conditions

Hemophilia B

Outcome Measures

Primary Outcomes (1)

• Occurence of Factor IX (FIX) 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 exposure days (EDs) to rFIXFc. In addition, the incidence for all participants, regardless of their EDs to rFIXFc, 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 50 weeks +/- 7 days, or up to 50 EDs if reached prior to Week 50

Secondary Outcomes (15)

• Annualized Bleeding Rate

  Up to 50 weeks +/- 7 days (efficacy period as defined in description)

• Annualized Joint Bleeding Rate (Spontaneous)

  Up to 50 weeks +/- 7 days (efficacy period as defined in description)

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

  Up to 50 weeks +/- 7 days

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

  Up to 50 weeks +/- 7 days

• Annualized rFIXFc Consumption by Type of Injection

  Up to 50 weeks +/- 7 days (efficacy period as defined in description)

Study Arms (1)

rFIXFc Prophylaxis

EXPERIMENTAL

At Baseline and at Day 1, participants receive a single intravenous (IV) injection of prestudy FIX and rFIXFc, respectively, over 10 (±5) minutes at a dose of 50 IU/kg. Immediately after the last PK sampling, the first prophylactic dose of approximately 50 to 60 IU/kg will be administered in clinic as an IV injection. Dose could be increased or decreased in increments of 10 IU/kg; increases to a maximum of 100 IU/kg and frequency of administration to a maximum of twice weekly, were allowed as indicated.

Drug: rFIXFc; Drug: FIX

Interventions

rFIXFc DRUG

Vials of rFIXFc 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: BIIB029, recombinant coagulation factor IX Fc fusion protein, Alprolix®

rFIXFc Prophylaxis

FIX DRUG

Vials of prestudy FIX (provided by the participants) 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.

Also known as: Factor IX

rFIXFc Prophylaxis

Eligibility Criteria

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

You may qualify if:

• Severe hemophilia B defined as ≤ 2 IU/dl (≤ 2%) endogenous FIX
• Male \< 12 years and weight ≥ 13 kg
• History of at least 50 documented prior exposure days to FIX
• No history of, or currently detectable, inhibitor

You may not qualify if:

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

Sponsors & Collaborators

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

Study Sites (15)

Research Site

Phoenix, Arizona, United States

Location

Research Site

Sacramento, California, United States

Location

Research Site

Atlanta, Georgia, United States

Location

Research Site

Honolulu, Hawaii, United States

Location

Research Site

Indianapolis, Indiana, United States

Location

Research Site

East Lansing, Michigan, United States

Location

Research Site

Pittsburgh, Pennsylvania, United States

Location

Research Site

Parkville, Victoria, Australia

Location

Research Site

Subiaco, Western Australia, Australia

Location

Research Site

Dublin, Ireland

Location

Research Site

Utrecht, Netherlands

Location

Research Site

Johannesburg, South Africa

Location

Research Site

Basingstoke, United Kingdom

Location

Research Site

Cambridge, United Kingdom

Location

Research Site

London, United Kingdom

Location

Related Publications (2)

• Shapiro AD, Kulkarni R, Ragni MV, Chambost H, Mahlangu J, Oldenburg J, Nolan B, Ozelo MC, Foster MC, Willemze A, Barnowski C, Jain N, Winding B, Dumont J, Lethagen S, Barnes C, Pasi KJ. Post hoc longitudinal assessment of the efficacy and safety of recombinant factor IX Fc fusion protein in hemophilia B. Blood Adv. 2023 Jul 11;7(13):3049-3057. doi: 10.1182/bloodadvances.2022009230.

  PMID: 36848635 DERIVED

• Fischer K, Kulkarni R, Nolan B, Mahlangu J, Rangarajan S, Gambino G, Diao L, Ramirez-Santiago A, Pierce GF, Allen G. Recombinant factor IX Fc fusion protein in children with haemophilia B (Kids B-LONG): results from a multicentre, non-randomised phase 3 study. Lancet Haematol. 2017 Feb;4(2):e75-e82. doi: 10.1016/S2352-3026(16)30193-4.

  PMID: 28159192 DERIVED

MeSH Terms

Conditions

Hemophilia B

Interventions

factor IX Fc fusion protein; Factor IX

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; Genetic Diseases, X-Linked

Intervention Hierarchy (Ancestors)

Enzyme Precursors; Enzymes and Coenzymes; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Protein Precursors; Biological Factors

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: September 16, 2011
• First Posted: September 27, 2011
• Study Start: June 1, 2012
• Primary Completion: November 1, 2014
• Study Completion: November 1, 2014
• Last Updated: December 19, 2020
• Results First Posted: June 18, 2015

Record last verified: 2018-08

Locations

ZA (1); GB (3); AU (2); US (7); IE (1); NL (1)