Pharmacokinetics of rFVIIIFc at Two Vial Strengths

NCT02083965 | Completed Phase 1 Results

• 2 other identifiers: 997HA3072013-003013-18
• Study Type: interventional
• Target: 19
• Locations: 3 countries
• Sites: 8

Brief Summary

The primary objective of the study is to characterize the pharmacokinetics (PK) of rFVIIIFc administered at vial strengths of 1000 and 3000 IU in subjects with severe hemophilia A. The secondary objective of the study is to evaluate the safety of rFVIIIFc beyond the PK assessment for up to 6 months for a continued treatment period.

Conditions

Severe Hemophilia A

Outcome Measures

Primary Outcomes (2)

• Area Under the Concentration-time Curve From Time Zero to Infinity (AUCinf) as Measured by Activated Partial Thromboplastin Time (aPTT) Clotting Assay

  Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0 - ∞).

  Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

• Incremental Recovery (IR, K Value) as Estimated From the FVIII Activity Data Measured by aPTT Clotting Assay

  The rise in FVIII activity in IU/dL per unit dose administered in IU/kg (IR, K value), as estimated from the FVIII activity data.

  Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

Secondary Outcomes (25)

• Maximum Activity (Cmax) as Measured by the aPTT Clotting Assay

  Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

• Half-life (t½) as Measured by aPTT Clotting Assay

  Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

• Clearance (CL) as Measured by the aPTT Clotting Assay

  Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

• Volume of Distribution at Steady State (Vss) as Measured by the aPTT Clotting Assay

  Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

• Mean Residence Time (MRT) as Measured by the aPTT Clotting Assay

  Predose, 0.5 hour (+-5 minutes); 1 hour and 6 hours (+-10 minutes); and 24, 48, 72, and 96 hours (+-60 minutes) after each injection

Study Arms (2)

rFVIIIFc 1000 / 3000 PK Assessment

EXPERIMENTAL

A single intravenous (IV) injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator.

Biological: rFVIIIFc

rFVIIIFc 3000 / 1000 PK Assessment

EXPERIMENTAL

A single IV injection of rFVIIIFc 50 IU/kg at a strength of 3000 IU/vial followed by a single IV injection of rFVIIIFc 50 IU/kg at a strength of 1000 IU/vial. Following the PK assessment, participants will receive either an episodic (on-demand) regimen with doses between 20 and 50 IU/kg based on the severity of the bleeding episode, or 1 of 2 prophylactic regimens: 50 IU/kg every 3 to 5 days or 65 IU/kg weekly. Participants will be allowed to switch from one regimen to another if approved by the Investigator.

Biological: rFVIIIFc

Interventions

rFVIIIFc BIOLOGICAL

Administered as specified in the treatment arm.

Also known as: Eloctate, antihemophilic factor [recombinant] FC fusion protein, recombinant coagulation factor VIII Fc fusion protein, efmoroctocog alfa, BIIB031, Elocta

rFVIIIFc 1000 / 3000 PK Assessment; rFVIIIFc 3000 / 1000 PK Assessment

Eligibility Criteria

• Age: 12 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Have severe hemophilia A
• Previously treated subject, defined as having at least 150 documented prior exposure days to any recombinant and/or plasma-derived FVIII and/or cryoprecipitate products (other than any use of rFVIIIFc- study drug or commercial product) 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 subjects.
• No measurable inhibitor activity using the Nijmegen-modified Bethesda assay at Screening.
• Platelet count ≥100,000 platelets/μL at screening
• CD4 lymphocytes \>200 mm3 if known as HIV antibody positive at screening.
• Viral load of \<400 copies/mL if known HIV antibody positive at screening.

You may not qualify if:

• Subject is at high risk of bleeding during the 5-day period between the first and second injections for PK analyses, as per Investigator discretion.
• Previous treatment with rFVIIIFc as study drug or commercial product.
• Other coagulation disorder(s) in addition to hemophilia A.
• History of hypersensitivity or anaphylaxis associated with any FVIII or IV immunoglobulin administration.
• Currently taking (or likely to require during the study) acetylsalicylic acid (ASA), except for low-dose ASA as prophylaxis (other nonsteroidal anti-inflammatory drugs are permitted).
• Concurrent systemic treatment with immunosuppressive drugs within 12 weeks prior to Day 1. Exceptions to this include: ribavirin for treatment of hepatitis C virus (HCV), and/or systemic steroids (a total of 2 courses of pulse treatments lasting no more than 7 days at a dose of ≤1 mg/kg within 12 weeks prior to Day 1) and/or inhaled steroids.

Sponsors & Collaborators

• Bioverativ Therapeutics Inc.: lead

Study Sites (8)

Research Site

Los Angeles, California, United States

Location

Research Site

Salt Lake City, Utah, 84101, United States

Location

Research Site

Seattle, Washington, United States

Location

Research Site

Herston, Australia

Location

Research Site

Perth, Australia

Location

Research Site

Basingstoke, United Kingdom

Location

Research Site

Cambridge, United Kingdom

Location

Research Site

London, United Kingdom

Location

MeSH Terms

Conditions

Hemophilia A

Interventions

factor VIII-Fc fusion protein

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Bioverativ Study Medical Director
• Organization: Bioverativ

clinicaltrials@bioverativ.com

Study Officials

• Medical Director

  Bioverativ Therapeutics Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2014
• First Posted: March 11, 2014
• Study Start: March 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: May 1, 2015
• Last Updated: December 19, 2020
• Results First Posted: August 19, 2016

Record last verified: 2017-05

Locations

AU (2); US (3); GB (3)