An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic FVIII in Patients With Severe Hemophilia A

CSL Behring175 enrolled

Overview

This is an open-label, non-randomized, efficacy, safety and pharmacokinetic (PK) study comparing octocog alfa and rVIII-SingleChain. The study consists of three parts, a PK period (Part 1), a continuation of dosing safety and efficacy period (Part 2) and a safety, efficacy, and repeat PK period (Part 3) and also includes a surgical sub-study for subjects enrolled in Parts 2 and 3.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

175

Conditions

Hemophilia A

Interventions

rVIII-SingleChainBIOLOGICAL

In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg recombinant, single-chain coagulation factor VIII (rVIII-SingleChain) preceded by a 4-day washout period. In Parts 2 and 3 of the study, subjects received repeat injections of rVIII-SingleChain either as an on-demand or prophylaxis regimen at a dose and frequency determined by their study doctor. Subjects participating in the Part 3 PK analyses received a single infusion of 50 IU/kg rVIII-SingleChain and a repeat dose of the same strength of rVIII-SingleChain after 3 to 6 months. Subjects from Parts 2 and 3 participating in the surgical substudy received an individualized dose regimen of rVIII-SingleChain, based on the type of surgery and the clinical status of the subject.

Octocog alfaBIOLOGICAL

In Part 1 of the study, subjects received a single intravenous infusion of 50 IU/kg of octocog alfa preceded by a 4-day washout period. Octocog alfa is the international nonproprietary name (INN) for recombinant human coagulation factor VIII.

Eligibility

Sex: MALEMin age: 12 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Diagnosis of severe hemophilia A defined as \<1% FVIII:C documented in medical records. * Males between 18 and 65 years of age (Parts 1 and 2). * Males between 12 and 65 years of age (Part 3). * Subjects who have received or are currently receiving FVIII products (plasma-derived and/or recombinant FVIII) and have had \>150 exposure days (EDs) with a FVIII product * Written informed consent for study participation obtained before undergoing any study specific procedures. Exclusion Criteria: * Any history of or current FVIII inhibitors * Any first order family history of FVIII inhibitors * Use of an Investigational Medicinal Product within 30 days prior to the first rVIII-SingleChain administration. * Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain or reference product. * Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein. * Any known congenital or acquired coagulation disorder other than congenital FVIII deficiency. * Platelet count \< 100,000/µL at screening. * Human immunodeficiency virus (HIV) positive subjects with a CD4 count \< 200/mm3, in their medical history or at screening if available results are older than one year. (HIV positive subjects may participate in the study and antiviral therapy are permitted, at the discretion of the Investigator). * Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment. * Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) values \> 5 times (x) the upper limit of normal (ULN) at Screening. * Subjects with serum creatinine values \> 2 x ULN at Screening. * Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months prior to Day 1. * Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months prior to Day 1.

Locations (56)

Outcomes

Primary Outcomes

Treatment Success

The investigator rated the efficacy of the treatment based on a 4-point rating scale "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point; the percentage of bleeding events with a rating of excellent or good and the 95% confidence interval are presented. The denominator includes all treated bleeding events. The 95% confidence interval is based on a model to account for within-subject correlation.

Time frame: Up to 24 months

Inhibitor Formation to FVIII

Number of subjects who develop inhibitors to FVIII

Time frame: Up to 24 months

Annualized Spontaneous Bleeding Rate

The annualized spontaneous bleeding rate (AsBR) was derived for each subject as follows: 365.25\*(number of spontaneous bleeding episodes requiring treatment) / (observed treatment period of interest).

Time frame: Up to 24 months

Treatment Success During the Peri-operative Surgical Sub-study

Subjects received rVIII-SingleChain before and during surgery based on the type of surgery and the clinical status of the subject. The investigator rated the efficacy of the treatment based on a 4-point surgical treatment rating scale of "excellent, good, moderate or poor/no response". Efficacy ratings of "excellent" or "good" were considered treatment success for this end point. The rate of success, defined as the percentage of surgeries with a rating of excellent or good for hemostatic efficacy on the surgical treatment scale is presented for the Surgical Population, based on the total number of surgeries (N=16) as denominator.

Time frame: From the start of surgery through the post-operative recovery (generally up to 14 days after surgery)

Secondary Outcomes

AUC0-∞ (Part 1)

AUC0-∞ (AUC from 0 extrapolated to infinity) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.

Data from ClinicalTrials.gov

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