Clinical trial NCT00162019: Pharmacokinetics, Efficacy and Safety Study of IMMUNATE SD (Human Plasma-Derived Coagulation Factor VIII Concentrate) in Hemophilia A Patients
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hemophilia A
Keywords: Factor VIII Deficiency
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2005-09-13
Enrollment: 56
Sex: MALE
Minimum age (years): 12
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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.


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

Primary outcomes:
measure: To compare the PK parameters of IMMUNATE S/D and IMMUNATE in subjects with severe hemophilia A (baseline factor VIII <= 1%)
timeFrame: 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.
measure: 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
timeFrame: 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.
measure: 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
timeFrame: Post-Infusion for a minimum of 27 weeks ±7 days or at least 50 treatment EDs, whichever occurs first.
measure: 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
timeFrame: Post-Infusion for a minimum of 27 weeks ±7 days or at least 50 treatment EDs, whichever occurs first.
measure: to assess the clinical safety of IMMUNATE S/D
timeFrame: Throughout the study period of approximately 18 months.
measure: to retrospectively explore the PK parameters of the VWF moiety of IMMUNATE S/D in subjects with severe hemophilia A (baseline factor VIII <= 1%).
timeFrame: Up to approximately 6.5 months
Secondary outcomes:
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: National Centre of Hematology and Transfusiology
city: Prague
country: Czechia
facility: University Hospital Motol
city: Budapest
country: Hungary
facility: National Medical Center, National Hemophilia Center
city: Warsaw
country: Poland
facility: Klinika Hemetologii I Onkologii Dzieciecej
city: Wroclaw
country: Poland
facility: Klinika Hematologii i Onkologii Dzieciecej
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: