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

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

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.

Study Overview

• Status: Completed
• Conditions: Hemophilia A
• Intervention / Treatment: Drug: Human Plasma-Derived Coagulation Factor VIII Concentrate (Virus Inactivated by Polysorbate 80 Treatment and Vapor Heat Treatment)

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1756
    • National Centre of Hematology and Transfusiology
• Czechia
  • Prague, Czechia, 150 06
    • University Hospital Motol
• Hungary
  • Budapest, Hungary, 1135
    • National Medical Center, National Hemophilia Center
• Poland
  • Warsaw, Poland, 00-5 76
    • Klinika Hemetologii I Onkologii Dzieciecej
  • Wroclaw, Poland, 50-345
    • Klinika Hematologii i Onkologii Dzieciecej

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Baxalta now part of Shire

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2003
• Primary Completion (Actual): August 24, 2004
• Study Completion (Actual): August 24, 2004

Study Registration Dates

• First Submitted: September 8, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (Estimate): September 13, 2005

Study Record Updates

• Last Update Posted (Actual): April 29, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: Factor VIII Deficiency
• Additional Relevant MeSH Terms: Hematologic Diseases; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Blood Coagulation Disorders; Hemophilia A; Coagulants; Factor VIII
• Other Study ID Numbers: 040201