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

Phase 3

Completed

• Conditions: Hemophilia A

• Registration Number: NCT00162019
• Lead Sponsor: Baxalta now part of Shire

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2003-03-31
• Primary Completion: 2004-08-24
• Study Completion: 2004-08-24
• Study First Submitted: 2005-09-08
• Study First Submitted QC: 2005-09-12
• Study First Posted: 2005-09-13
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-28
• Last Update Posted: 2021-04-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 56

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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 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
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.

Trial Locations

Locations (5)

National Centre of Hematology and Transfusiology; 🇧🇬 Sofia, Bulgaria

National Medical Center, National Hemophilia Center; 🇭🇺 Budapest, Hungary

University Hospital Motol; 🇨🇿 Prague, Czechia

Klinika Hemetologii I Onkologii Dzieciecej; 🇵🇱 Warsaw, Poland

Klinika Hematologii i Onkologii Dzieciecej; 🇵🇱 Wroclaw, Poland