Trial record 1 of 8 for:    rFVIIIFc
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Pharmacokinetics and Safety of rFVIIIFc Manufactured at 15,000 L (15K) Scale (15K Scale Up)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2015 by Biogen
Sponsor:
Collaborator:
Swedish Orphan Biovitrum
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT02502149
First received: May 29, 2015
Last updated: July 16, 2015
Last verified: July 2015
  Purpose

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 subjects 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.


Condition Intervention Phase
Severe Hemophilia A
Biological: rFVIIIFc
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
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

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    Area under the concentration-time curve from time zero to infinity (AUCinf), incremental recovery (IR) following dosing of rFVIIIFc manufactured at 2K scale (PK1) and for pharmacokinetic assessment 2 with rFVIIIFc manufactured at 15K scale (PK2)

  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Development of inhibitors as measured by the Nijmegen-modified Bethesda assay [ Time Frame: pre-dose, week 13 of PK2 and 26 weeks post PK2 ] [ Designated as safety issue: Yes ]
  • Number of participants that experience adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 26 weeks post PK injection ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: September 2015
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rFVIIIFc (15K scale) 1000 IU vial
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).
Biological: rFVIIIFc
As per arm description
Other Names:
  • Eloctate; BIIB031; efmoroctocog alfa; recombinant coagulation factor VIII Fc fusion protein; antihemophilic factor [recombinant]
  • Fc fusion protein
Experimental: rFVIIIFc (15K scale) Higher Strength vial
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).
Biological: rFVIIIFc
As per arm description
Other Names:
  • Eloctate; BIIB031; efmoroctocog alfa; recombinant coagulation factor VIII Fc fusion protein; antihemophilic factor [recombinant]
  • Fc fusion protein

Detailed 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 subjects will be offered enrollment into a long-term safety and efficacy extension study (8HA01EXT [NCT01454739]).

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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 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.
  • 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 IV immunoglobulin administration.

NOTE: Other protocol-defined inclusion/exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02502149

Contacts
Contact: Biogen clinicaltrials@biogen.com

Sponsors and Collaborators
Biogen
Swedish Orphan Biovitrum
Investigators
Study Director: Medical Director Biogen
  More Information

No publications provided

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02502149     History of Changes
Other Study ID Numbers: 997HA309, 2014-003895-21
Study First Received: May 29, 2015
Last Updated: July 16, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Biogen:
rFVIIIFc
Eloctate
Hemophilia

Additional relevant MeSH terms:
Hemophilia A
Hemophilia B
Blood Coagulation Disorders
Blood Coagulation Disorders, Inherited
Coagulation Protein Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hematologic Diseases
Hemorrhagic Disorders
Factor VIII
Coagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on September 01, 2015