An Open-label Safety, Efficacy and Pharmacokinetic Study of a Recombinant FVIII Compared to Recombinant Human Antihemophilic FVIII in Patients With Severe Hemophilia A
- Conditions
- Hemophilia A
- Interventions
- Biological: rVIII-SingleChainBiological: Octocog alfa
- Registration Number
- NCT01486927
- Lead Sponsor
- CSL Behring
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Male
- Target Recruitment
- 175
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Recombinant Factor VIII (rFVIII) Octocog alfa - Recombinant Factor VIII (rFVIII) rVIII-SingleChain -
- Primary Outcome Measures
Name Time Method Annualized Spontaneous Bleeding Rate Up to 24 months 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).
Treatment Success During the Peri-operative Surgical Sub-study From the start of surgery through the post-operative recovery (generally up to 14 days after surgery) 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.
Inhibitor Formation to FVIII Up to 24 months Number of subjects who develop inhibitors to FVIII
Treatment Success Up to 24 months 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.
- Secondary Outcome Measures
Name Time Method AUC0-∞ (Part 1) Before infusion and at up to 10 time points within 72 hours of infusion 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.
Cmax (Part 1) Before infusion and at up to 10 time points within 72 hours of infusion Cmax of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Tmax (Part 1) Before infusion and at up to 10 time points within 72 hours of infusion Tmax = time of Cmax (with correction for subject's predose plasma FVIII activity) after a single infusion of octocog alfa and rVIII-SingleChain.
Half-life (t1/2) (Part 1) Before infusion and at up to 10 time points within 72 hours of infusion. Half-life (t1/2) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Mean Residence Time (MRT) (Part 1) Before infusion and at up to 10 time points within 72 hours of infusion Mean residence time (MRT) of a single infusion of octocog alfa and rVIII-SingleChain without correction for subject's predose plasma FVIII activity.
Clearance (Cl) (Part 1) Before infusion and at up to 10 time points within 72 hours of infusion Clearance (Cl) 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.
Volume of Distribution at Steady-state (Vss) (Part 1) Before infusion and at up to 10 time points within 72 hours of infusion Volume of distribution at steady-state (Vss) 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.
Incremental Recovery (Part 1) At 30 minutes after infusion Incremental recovery of a single infusion of octocog alfa and rVIII-SingleChain with correction for subject's predose plasma FVIII activity. FVIII activity values for octocog alfa are dose-adjusted for chromogenic potency.
Annualized Bleeding Rate for Total Bleeds and Traumatic Bleeds Up to 24 months The annualized bleeding rate was derived for each subject as follows: 365.25\*(number of bleeding episodes requiring treatment) / (observed treatment period of interest).
Proportion of Bleeding Episodes Requiring 1, 2, 3 or > 3 Infusions of rVIII-SingleChain to Achieve Hemostasis During the study (up to 24 months; assessed at Months 1, 2, 3, 4, 5, 6, 9, 12, 15, 18, 21 and 24) Percentage of bleeding episodes requiring 1, 2, 3 or \> 3 infusions of rVIII-SingleChain to achieve hemostasis. The denominator includes all treated bleeding episodes.
Trial Locations
- Locations (1)
Study Site
🇬🇧London, United Kingdom