Pharmacokinetics of rFVIIIFc at Two Vial Strengths

Bioverativ

Status and phase: Completed; Phase 1

Conditions: Severe Hemophilia A

Treatments: Biological: rFVIIIFc

Study type: Interventional

Funder types: Industry

Identifiers

NCT02083965

997HA307

2013-003013-18 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

This is a randomized, open-label, crossover study during which each participant receives a single injection of rFVIIIFc from 2 different vial concentrations (PK assessment). After the PK assessment, participants are provided with rFVIIIFc for either prophylactic or episodic (on-demand) treatment for up to 6 months.

Enrollment: 19 patients

Sex: Male

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• 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.

Key Exclusion Criteria:

• 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.

NOTE: Other protocol-defined inclusion/exclusion Criteria May Apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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19 participants in 2 patient groups

rFVIIIFc 1000 / 3000 PK Assessment

Experimental group

Description:

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.

Treatment:

Biological: rFVIIIFc

rFVIIIFc 3000 / 1000 PK Assessment

Experimental group

Description:

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.

Treatment:

Biological: rFVIIIFc