Brief Title
Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in Previously Treated Subjects With Severe Hemophilia A
Official Title
A-LONG: An Open-Label, Multicenter Evaluation of the Safety, Pharmacokinetics, and Efficacy of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc) in the Prevention and Treatment of Bleeding in Previously Treated Subjects With Severe Hemophilia A
Brief Summary
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.
Detailed 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).
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Incidence Rate of FVIII Inhibitor Development
Secondary Outcome
Comparison of Annualized Bleeding Rates: Arm 2 Versus Arm 3
Condition
Severe Hemophilia A
Intervention
Factor VIII (rFVIIIFc)
Study Arms / Comparison Groups
Individualized (Tailored) Prophylaxis
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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
165
Start Date
November 2010
Completion Date
August 2012
Primary Completion Date
August 2012
Eligibility Criteria
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
Gender
Male
Ages
12 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Medical Director, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT01181128
Organization ID
997HA301
Responsible Party
Sponsor
Study Sponsor
Bioverativ Therapeutics Inc.
Collaborators
Swedish Orphan Biovitrum
Study Sponsor
Medical Director, Study Director, Bioverativ Therapeutics Inc.
Verification Date
July 2017