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

Bioverativ

Status and phase

Completed

Phase 3

Conditions

Severe Hemophilia A

Treatments

Drug: Advate®

Drug: Factor VIII (rFVIIIFc)

Study type

Interventional

Funder types

Industry

Identifiers

NCT01181128

997HA301

Details and patient eligibility

About

The primary objectives of this study are: to evaluate the safety and tolerability of rFVIIIFc administered as a prophylaxis (Arm 1), weekly (Arm 2), on-demand (Arm 3), and surgical treatment regimen; to evaluate the efficacy of the rFVIIIFc tailored prophylaxis regimen (Arm 1); to evaluate the efficacy of rFVIIIFc administered as an on-demand (Arm 3) and surgical treatment regimen. The secondary objectives of this study are: to characterize the PK profile of rFVIIIFc and compare the PK of rFVIIIFc with the currently marketed product, Advate®; to characterize the range of dose and schedules required to adequately prevent bleeding in a prophylaxis regimen, maintain hemostasis in a surgical setting, or to treat bleeding episodes in an on-demand, weekly treatment, or prophylaxis setting.

Full description

Participants are assigned to one of three treatment regimens: 1) a tailored prophylaxis regimen, 2) a weekly dosing regimen, or 3) an on-demand regimen. Treatment continued for 28 (±2) to 52 (±2) weeks. PK assessments for all participants are conducted on varying schedules, according to participants' group assignments. Additionally, two subgroups are defined. One subgroup of participants undergo PK profiling with a single dose of the comparator Advate®. A second subgroup consists of participants from any of the treatment arms that required surgery during the study. Depending upon country location, participants might have the option of continuing treatment within study 8HA01EXT (NCT01454739).

Enrollment

165 patients

Sex

Male

Ages

12+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male, ≥12 years of age with weight at least 40 kg
Diagnosed with severe hemophilia A, defined as <1 IU/dL (<1%) endogenous Factor VIII)
History of at least 150 documented prior exposure days to any Factor VIII product
Platelet count ≥100,000 cells/μL

Exclusion criteria

History of Factor VIII inhibitors
Kidney and liver dysfunction
Diagnosed with other coagulation disorder(s) in addition to hemophilia A
Prior history of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

165 participants in 3 patient groups

Individualized (Tailored) Prophylaxis

Experimental group

Description:

On rFVIIIFc Day 0, all participants underwent pharmacokinetic (PK) analysis with 50 IU/kg rFVIIIFc to estimate their PK parameters and guide the appropriate dose or interval of dosing. A subset of participants (Sequential PK subgroup) also had PK analyses performed with a single dose of 50 IU/kg Advate (Advate Day 0) within 8 weeks prior to rFVIIIFc Day 0. A \>= 96 hour washout was performed before the PK dose of Advate or rFVIIIFc was administered. Repeat PK profiling with a single dose of 50 IU/kg rFVIIIFc was conducted at Week 14 or after 12 to 24 weeks of prophylaxis with rFVIIIFc. After PK assessments, all participants started twice weekly treatment with 25 IU/kg of rFVIIIFc via intravenous (IV) injection on Day 1 and 50 IU/kg on Day 4, followed by individualized dose and interval modification within the range of 25 to 65 IU/kg every 3 to 5 days, as determined by rFVIIIFc PK analysis, to maintain a trough level of 1% to 3% (or higher, as clinically indicated) FVIII activity.

Treatment:

Drug: Factor VIII (rFVIIIFc)

Drug: Advate®

Weekly Prophylaxis

Experimental group

Description:

65 IU/kg of rFVIIIFc via IV injection every 7 days

Treatment:

Drug: Factor VIII (rFVIIIFc)

Episodic (On-Demand) Dosing

Experimental group

Description: