Hemophilia A
Conditions
Keywords
Factor VIII Deficiency
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.
Interventions
DRUGHuman Plasma-Derived Coagulation Factor VIII Concentrate (Virus Inactivated by Polysorbate 80 Treatment and Vapor Heat Treatment)
Sponsors
Baxalta now part of Shire
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
12 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| 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 |
Countries
Bulgaria, Czechia, Hungary, Poland
Outcome results
None listed