Pharmacokinetics, Efficacy and Safety Study of IMMUNATE SD (Human Plasma-Derived Coagulation Factor VIII Concentrate) in Hemophilia A Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to evaluate whether IMMUNATE S/D is effective and safe in the treatment of hemophilia A patients. The study consists of 3 parts: Part 1 is a pharmacokinetic comparison of IMMUNATE S/D and its predecessor IMMUNATE. Part 2 is an evaluation of efficacy and safety of IMMUNATE S/D. Part 3 is a pharmacokinetic study of IMMUNATE S/D.

Official Title
-----------------
Phase 3, Prospective, Multicenter Study to Evaluate the Pharmacokinetics, Immunogenicity, Safety, and Efficacy of IMMUNATE Solvent Detergent (IMMUNATE SD) in Previously Treated Patients With Severe or Moderately Severe Hemophilia A

Conditions
-----------------
Hemophilia A

Intervention / Treatment
-----------------
* Drug: Human Plasma-Derived Coagulation Factor VIII Concentrate (Virus Inactivated by Polysorbate 80 Treatment and Vapor Heat Treatment)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - Plasma factor VIII level as follows: for Parts 1 & 3: Subjects with severe hemophilia A (plasma baseline factor VIII level <= 1% measured at time of screening) for Part 2: Subjects with severe (plasma baseline factor VIII level <= 1% measured at time of screening) or moderately severe hemophilia A (plasma baseline factor VIII level <= 2% measured at time of screening) Males >= 12 but <= 65 years of age >= 35 kg body weight Previously treated with factor VIII concentrate(s) for a minimum of 150 exposure days (as documented in the subject's medical history) Evidence of a protective titer to HAV and HBV at the time of screening Immunocompetent as defined by a CD4+ lymphocyte count >400/mm3 and an absolute neutrophil count (ANC) >1500 Signed informed consent obtained from subject or legally authorized representative Exclusion Criteria: Documented history of inhibitor to factor VIII with a titer >= 0.8 BU Current evidence of inhibitor to factor VIII with a titer >= 0.8 BU, measured at the time of screening Abnormal renal function (serum creatinine > 1.5 mg/dL) HIV-seropositive individuals with any of the following at the time of screening: CD4+ lymphocyte count >400/mm3 AIDS-related complex symptomatic AIDS Note: HIV-seropositive subjects with an absolute CD4+ lymphocyte count > 400/mm3 are eligible to participate. HIV-seropositive subjects receiving highly active anti-retroviral therapy (HAART) regimens are eligible for enrollment if they are not excluded by the above criteria Active hepatic disease (ALT and AST levels > 5 times the upper limit of normal) Clinical or laboratory evidence of hepatic cirrhosis including (but not limited to) a recent and persistent INR (international normalized ratio) > 1.4, the presence of splenomegaly and/or significant spider angiomata on physical exam, and/or a history of esophageal hemorrhage or documented esophageal varices Known hypersensitivity to IMMUNATE The subject is currently participating in another investigational drug study, or has participated in any clinical study involving an investigational drug within 30 days of study entry The subject is currently receiving, or is scheduled to receive during the course of the study, an immunomodulating drug other than anti-retroviral chemotherapy (e.g., a-interferon, steroids at a dose greater than 10 mg/day) The subject is identified by the investigator as being unable or unwilling to perform study procedures

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Human Plasma-Derived Coagulation Factor VIII Concentrate (Virus Inactivated by Polysorbate 80 Treatment and Vapor Heat Treatment)|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To compare the PK parameters of IMMUNATE S/D and IMMUNATE in subjects with severe hemophilia A (baseline factor VIII <= 1%) |  | Within 30 minutes pre-infusion; and at 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 9 hours, 24 hours, 28 hours, 32 hours, and 48 hours post-infusion. | 
| to re-evaluate PK parameters for IMMUNATE S/D after a minimum of 14 weeks ± 7 days of treatment with at least 10 exposure days with IMMUNATE S/D |  | Within 30 minutes pre-infusion; and at 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 9 hours, 24 hours, 28 hours, 32 hours, and 48 hours post-infusion. | 
| to monitor the incidence of factor VIII inhibitor development over a minimum of 27 weeks ± 7 days or at least 50 exposure days, whichever occurs first, in all subjects |  | Post-Infusion for a minimum of 27 weeks ±7 days or at least 50 treatment EDs, whichever occurs first. | 
| to evaluate the hemostatic efficacy of IMMUNATE S/D in the management of acute bleeding episodes and in the perioperative management of surgical prophylaxis, if required, over the same period of treatment |  | Post-Infusion for a minimum of 27 weeks ±7 days or at least 50 treatment EDs, whichever occurs first. | 
| to assess the clinical safety of IMMUNATE S/D |  | Throughout the study period of approximately 18 months. | 
| to retrospectively explore the PK parameters of the VWF moiety of IMMUNATE S/D in subjects with severe hemophilia A (baseline factor VIII <= 1%). |  | Up to approximately 6.5 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Factor VIII Deficiency