Overview

This trial is active, not recruiting.

Condition severe hemophilia a
Treatment rfviiifc
Phase phase 3
Sponsor Biogen
Collaborator Swedish Orphan Biovitrum
Start date August 2015
End date April 2017
Trial size 24 participants
Trial identifier NCT02502149, 2014-003895-21, 997HA309

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 a higher strength vial; and to evaluate the safety of rFVIIIFc manufactured at the 15K scale.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacokinetics study
Intervention model parallel assignment
Masking open label
Arm
(Experimental)
Single injection of rFVIIIFc (current 2K scale) followed by 2 single injections of rFVIIIFc (15K scale) 1000 IU vial at PK2 and PK3 timepoints. Prophylaxis and treatment of bleeding episodes is permitted during the 26 week treatment period using the rFVIIIFc (15K scale).
rfviiifc Eloctate; BIIB031; efmoroctocog alfa; recombinant coagulation factor VIII Fc fusion protein; antihemophilic factor [recombinant]
As per arm description
(Experimental)
Single injection of rFVIIIFc (current 2K scale) followed by 2 single injections of rFVIIIFc high strength vial (15K scale) at PK2 and PK3 timepoints. Prophylaxis and treatment of bleeding episodes is permitted during the 26 week treatment period using the rFVIIIFc (15K scale).
rfviiifc Eloctate; BIIB031; efmoroctocog alfa; recombinant coagulation factor VIII Fc fusion protein; antihemophilic factor [recombinant]
As per arm description

Primary Outcomes

Measure
Area under the concentration time curve from time zero to infinity (AUCinf) for PK1 and PK2
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
Incremental recovery (IR) for PK1 and PK2
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr

Secondary Outcomes

Measure
area under the concentration-time curve from time zero to infinity (AUCinf) for PK2 and PK3
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
incremental recovery (IR) for PK2 and PK3
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
the maximum rFVIIIFc activity (Cmax) for PK2 and PK3
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
half-life (t½) for PK2 and PK3
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
clearance (CL) for PK2 and PK3
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
volume of distribution at steady state (Vss) at PK2 and PK3
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
mean residence time (MRT) at PK2 and PK3
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
AUCinf of rFVIIIFc manufactured at the 15K scale at different vial strengths
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
IR of rFVIIIFc manufactured at the 15K scale at different vial strengths
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
Cmax of rFVIIIFc manufactured at the 15K scale at different vial strengths
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
t½ of rFVIIIFc manufactured at the 15K scale at different vial strengths
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
CL of rFVIIIFc manufactured at the 15K scale at different vial strengths
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
Vss of rFVIIIFc manufactured at the 15K scale at different vial strengths
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
MRT of rFVIIIFc manufactured at the 15K scale at different vial strengths
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
Cmax at PK1 and Pk2
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
t½ at PK1 and Pk2
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
CL at PK1 and Pk2
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
Vss at PK1 and Pk2
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
MRT at PK1 and Pk2
time frame: Pre-dose and post dose at: 0.5 hr, 1, hr, 6 hr, 24 hr, 48 hr, 72 hr and 96 hr
Development of inhibitors as measured by the Nijmegen-modified Bethesda assay
time frame: pre-dose, week 13 of PK2 and 26 weeks post PK2
Number of participants that experience adverse events (AEs) and serious adverse events (SAEs)
time frame: Up to 26 weeks post PK injection

Eligibility Criteria

Male participants at least 12 years old.

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 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.

Additional Information

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
Description PK assessments are in 3 phases: PK1: PK assessments following single injection of rFVIIIFc manufactured at the 2K scale. 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 a higher strength vial. 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 a higher strength vial. 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]).
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Biogen.