Study of Recombinant Factor IX Fc Fusion Protein (rFIXFc) in Participants With Hemophilia B

Bioverativ

Status and phase: Completed; Phase 3

Conditions: Severe Hemophilia B

Treatments: Drug: Factor IX (rFIXFc); Drug: rFIX

Study type: Interventional

Funder types: Industry

Identifiers

NCT01027364

2009-014295-21 (EudraCT Number)

998HB102

Details and patient eligibility

About

The primary objectives of the study were: to evaluate the safety and tolerability of rFIXFc; to evaluate the efficacy of rFIXFc in all treatment arms; to evaluate the effectiveness of prophylaxis over on-demand (episodic) therapy by comparing the annualized number of bleeding episodes between participants receiving rFIXFc on each prevention (prophylaxis) regimen and participants receiving rFIXFc on an episodic regimen. The secondary objectives of the study were: to evaluate and assess the pharmacokinetic (PK) parameter estimates of rFIXFc and rFIX (BeneFIX®) at baseline in the Sequential PK subgroup as well as rFIXFc at Week 26 (±1 week); to evaluate participants' response to treatment; to evaluate rFIXFc consumption.

Enrollment: 123 patients

Sex: Male

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and 12 years of age and older and weigh at least 40 kg
• Diagnosed with hemophilia B (baseline Factor IX level less than or equal to 2%)
• History of at least 100 exposure days to any Factor IX product
• Platelet count ≥100,000 cells/μL

Exclusion criteria

• History of Factor IX inhibitors
• Kidney or liver dysfunction
• Diagnosed with another coagulation defect other than hemophilia B
• Prior history of anaphylaxis associated with any Factor IX or intravenous (IV) immunoglobulin administration

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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123 participants in 4 patient groups

Fixed Weekly Interval

Experimental group

Description:

50 IU/kg rFIXFc via intravenous (IV) injection once every 7 days initially, then at a dose indicated by the participant's baseline pharmacokinetic (PK) assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial weekly dose of rFIXFc (50 IU/kg) were to be made based on baseline PK assessments, occurrence of spontaneous bleeding episodes, and the trough levels, which were to be monitored at Weeks 4, 16, 26, and 39. Prior to the first dose of rFIXFc, participants in the Sequential PK subgroup were to receive a single dose of 50 IU/kg BeneFIX administered IV in the clinic, followed by PK sampling. A single dose of 50 IU/kg rFIXFc was administered following a 120-hour washout from BeneFIX, followed by PK sampling for a baseline PK profiling. At Week 26 (±1 week) subjects were to receive a single dose of 50 IU/kg rFIXFc for repeat PK profiling.

Treatment:

Drug: rFIX

Drug: Factor IX (rFIXFc)

Individualized Interval

Experimental group

Description:

100 IU/kg rFIXFc via IV injection once every 10 days initially, then at an interval derived from the baseline PK assessment that ensured a target trough of 1% to 3% above baseline or higher, as clinically indicated. Adjustments to the initial 10-day interval were to be made based on baseline PK assessments and trough levels, which were monitored at Weeks 4, 16, 26, and 39.

Treatment:

Drug: Factor IX (rFIXFc)

On Demand

Experimental group

Description:

20 to 100 IU/kg rFIXFc via IV injection, or the dose indicated by the participant's baseline PK to target a plasma level of 20% to 100%, as needed for the treatment of mild to severe bleeding episodes

Treatment:

Drug: Factor IX (rFIXFc)

Surgery

Experimental group

Description:

The surgical period and dosing are dependent on the type of surgery the participant undergoes. Participants who started the study in one of the other treatment arms prior to surgery will return to the original treatment arm. Participants who joined the study in the Surgery arm will be assigned to one of the other treatment arms following post-operative rehabilitation.

Treatment:

Drug: Factor IX (rFIXFc)