Brief Title
Pharmacokinetics and Safety of rFVIIIFc Manufactured at 15,000 L (15K) Scale
Official Title
A Randomized, Open-Label Study to Evaluate the Pharmacokinetics and Safety of Recombinant Factor VIII Fc Fusion Protein (rFVIIIFc; BIIB031) Manufactured at 15K Scale and at Different Vial Strengths in Previously Treated Subjects With Severe Hemophilia A
Brief Summary
The primary objective of the study is to compare the pharmacokinetic (PK) of recombinant
coagulation factor VIII Fc fusion protein (rFVIIIFc) manufactured at the current scale of
2000 L (2K) to the PK of rFVIIIFc manufactured at the 15,000 L (15K) scale in previously
treated participants with severe hemophilia A. The secondary objectives are: to characterize
the PK of rFVIIIFc manufactured at the 15K scale at the 15K baseline and after 13 weeks of
treatment; to characterize the PK of rFVIIIFc manufactured at the 15K scale at 1000 IU/vial
and 6000 IU/vial strengths; and to evaluate the safety of rFVIIIFc manufactured at the 15K
scale.
Detailed Description
PK assessments are in 3 phases: Pharmacokinetic Assessment 1(PK1): PK assessments following
single injection of rFVIIIFc manufactured at the 2K scale. Pharmacokinetic Assessment 2
(PK2): PK assessments are made following a single injection of rFVIIIFc manufactured at the
15K scale where participants are randomized to the 1000 IU vial or 6000 IU/vial strengths.
Pharmacokinetic Assessment 3 (PK3): PK assessments are made following 13 weeks of rFVIIIFc
treatment manufactured at the 15K scale where participants are randomized to the 1000 IU vial
or 6000 IU/vial strengths. After study completion, in countries where rFVIIIFc is not
commercially available, eligible participants will be offered enrollment into a long-term
safety and efficacy extension study (8HA01EXT [NCT01454739]).
Study Phase
Phase 3
Study Type
Interventional
Primary Outcome
Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by One-stage Activated Partial Thromboplastin Time (aPTT) Clotting Assay for Pharmacokinetic Assessment 1 (PK1) and Pharmacokinetic Assessment 2 (PK2)
Secondary Outcome
Maximum Activity (Cmax) of rFVIIIFc as Measured by One-stage aPTT Clotting Assay for PK1 and PK2
Condition
Severe Hemophilia A
Intervention
rFVIIIFc
Study Arms / Comparison Groups
rFVIIIFc (15K scale) 1000 IU vial
Description: Single injection of rFVIIIFc (current 2K scale) followed by 2 single injections of rFVIIIFc (15K scale) 1000 IU vial at PK2 and PK3 timepoints. Participants will be on prophylaxis regimen along with treatment for bleeding episodes for 26 weeks of treatment period using the rFVIIIFc (15K scale) 1000 IU vial.
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
Biological
Estimated Enrollment
24
Start Date
August 2015
Completion Date
June 2017
Primary Completion Date
April 2017
Eligibility Criteria
Key Inclusion Criteria:
- Have severe hemophilia A, defined as <1 IU/dL (<1%) endogenous FVIII as determined by
one-stage clotting assay from the central laboratory at Screening.
- Previously treated subject, defined as having at least 150 documented prior exposure
days (EDs) to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate
products at Day 1. Fresh frozen plasma treatment must not be considered in the count
for documented exposure days.
- No history of a positive inhibitor test or clinical signs of decreased response to
FVIII administrations. Family history of inhibitors will not exclude the subject.
- No measurable inhibitor activity using the Nijmegen-modified Bethesda assay (>=0.6
Bethesda Unit per milliliter [BU/mL] is considered positive) at Screening.
Key Exclusion Criteria:
- Current enrollment in any interventional clinical study in which an investigational
drug or approved therapy for investigational use is administered within 30 days prior
to the Baseline Visit OR prior participation in any of the following Biogen studies:
998HA101 (NCT01027377), 997HA301 (NCT01181128), 8HA02PED (NCT01458106), 997HA307
(NCT02083965), and 8HA01EXT (NCT01454739).
- Previous participation in this study.
- Any concurrent clinically significant major disease that, in the opinion of the
Investigator or Biogen, makes the subject unsuitable for participation in the study.
- Other coagulation disorder(s) in addition to hemophilia A.
- History of hypersensitivity or anaphylaxis associated with FVIII or intravenous (IV)
immunoglobulin administration.
NOTE: Other protocol-defined inclusion/exclusion criteria may apply.
Gender
Male
Ages
12 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Medical Director, ,
Location Countries
Australia
Location Countries
Australia
Administrative Informations
NCT ID
NCT02502149
Organization ID
997HA309
Secondary IDs
2014-003895-21
Responsible Party
Sponsor
Study Sponsor
Bioverativ Therapeutics Inc.
Collaborators
Swedish Orphan Biovitrum
Study Sponsor
Medical Director, Study Director, Bioverativ Therapeutics Inc.
Verification Date
March 2018