A phase II/III, randomized, cross-over, open-label trial to demonstrate superiority of prophylaxis over on-demand therapy in previously treated subjects with severe hemophilia A treated with plasma protein-free recombinant FVIII formulated with sucrose (BAY 81-8973)
- Conditions
- Severe Hemophilia-A (< 1% FVIII:C)MedDRA version: 13.1Level: LLTClassification code 10060613Term: Hemophilia A (Factor VIII)System Organ Class: 10010331 - Congenital, familial and genetic disordersMedDRA version: 13.1Level: LLTClassification code 10053753Term: Hemophilia A without inhibitorsSystem Organ Class: 10010331 - Congenital, familial and genetic disordersMedDRA version: 13.1Level: LLTClassification code 10060612Term: Hemophilia ASystem Organ Class: 10010331 - Congenital, familial and genetic disorders
- Registration Number
- EUCTR2009-012150-20-CZ
- Lead Sponsor
- Bayer HealthCare AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 80
•Male, aged 12 to 65 years
•Severe hemophilia A, defined as < 1% FVIII:C as determined by one-stage clotting assay at the time of screening. If screening result turns out to be equal to or higher than 1%, then severe hemophilia A may be confirmed by one of the following (as of Amd 3):
Documented historical evidence from a recognized (certified) clinical laboratory (acceptable to GCL) demonstrating < 1% FVIII:C as determined by one-stage clotting assay
Assay results from a previous Bayer hemophilia clinical trial
•=150 exposure days (ED) in total with any recombinant FVIII or plasma-derived FVIII only. Cryoprecipitate and fresh frozen plasma treatments are not considered in this total. (as of Amd 1)
•Currently receiving episodic treatment with FVIII; and no regular prophylaxis for > 6 consecutive months in the previous 5 years
•No current evidence of inhibitor antibody as measured by the Nijmegen-modified Bethesda assay [<0.3 Bethesda units (BU/mL)] (as of Amd 1) in 2 consecutive samples and absence of clinical signs or symptoms of decreased response to FVIII administration. (First negative sample can be historical if obtained within 3 months prior to screening with a result of ? 0.6 BU/mL by a classical Bethesda assay. The testing for a second negative, confirmatory sample must, in all cases, be performed by a central laboratory using the Nijmegen test. If a first recent sample is not available, then testing for 2 negative samples must be performed by the central laboratory at least 1 week apart). Subjects may not receive FVIII within 72 hours (as of Amd 1) prior tothe collection of samples for inhibitor testing. The time period since the last FVIII injection should not be longer than 4 weeks.
•No history of FVIII inhibitor formation defined as inhibitor antibody <0.6 BU/mL by the Nijmegen-modified or classical Bethesday assay. However subjects with a maximum historical titer of 1.0 BU with the Classical Bethesda assay on no more than 1 occasion but with at least 3 subsequent (as of Amd 1) successive negative results (<0.6 BU) thereafter are also eligible.
•Willingness and ability to complete training in the use of the study electronic patient diary (EPD) by the subject or a surrogate (a caregiver or family member over 18 years of age). (as of Amd 1).
•Written informed consent by subject and parent/legal representative, if under age of consent per local regulation.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
•Presence of another bleeding disease that is different from hemophilia A (e.g., von Willebrand disease, hemophilia B)
•Thrombocytopenia (platelet count < 100 000/mm3)
•Abnormal renal function (serum creatinine > 2.0 mg/dL)
•Presence of active liver disease verified by medical history or persistent and increased alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5x the upper limit of normal (ULN) or severe liver disease as evidenced by an INR >4, hypoalbuminemia, and portal vein hypertension.
•Received treatment with immunomodulatory agents within the last 3 months prior to study entry or requires treatment during the study. [The following drugs are allowed: interferon-a treatment for hepatitis C virus (HCV), highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV), and or a total of 2 courses of pulse treatment with steroids for a maximum of 7 days at 1 mg/kg or less].
•Absolute CD4 lymphocyte cell count < 250 cells/?L (as of Amd 1).
•Receiving or has received other experimental drugs within 3 months prior to study entry, with the exception of Bayer Kogenate (Bayer factor VIII study drugs) received in studies within 2 weeks prior to study entry. (as of Amd 1)
•Requires any pre-medication to tolerate FVIII injections (e.g., antihistamines)
•Unwilling to comply with study visits or other protocol requirements or is not suitable for participation in this study for any reason, according to the Investigator
•Known hypersensitivity to hamster and/or mouse protein.
•Any subject who cannot forego at least 2-3 days without receiving FVIII for washout purposes. (as of Amd 3)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method