A two part randomized, cross-over, open-label trial to evaluate the pharmacokinetics, efficacy, and safety profile of plasma-protein free recombinant FVIII formulated with sucrose (BAY 81-8973) in previously treated subjects with severe hemophilia A under prophylaxis therapy.

• 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 disorders; MedDRA version: 13.1Level: LLTClassification code 10053753Term: Hemophilia A without inhibitorsSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 13.1Level: LLTClassification code 10060612Term: Hemophilia ASystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2009-012149-43-DK
• Lead Sponsor: Bayer HealthCare AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2010-08-09
• Last Update Posted: 28 October 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 60

Inclusion Criteria

• 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 6): Documented historical evidence from a recognized (certified)
clinical laboratory (acceptable to GCL) demonstrating < 1% FVIII:C as determined by one-stage clotting assay,
or 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 on-demand or any type of prophylaxis treatment regimen with any FVIII product.
• No current evidence of inhibitor antibody as measured by the Nijmegen modified Bethesda assay [<0.3
Bethesda units (BU/mL)] (as of Amd 5) 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. Second negative, confirmatory sample testing 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 5) prior to the collection of samples for inhibitor testing.
• No history of FVIII inhibitor formation, defined as inhibitor antibody < 0.6 BU/mL, by the Bethesda assay.
However, patients with a maximum historical titer of 1.0 BU (as of Amd 5) 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: 5
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 62
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• 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 significant portal vein hypertension in the judgment of the
Investigator. (as of Amd 5)
• 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/uL (as of Amd 5)
• 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 mouse protein.
• Any subject who cannot forego at least 3 days without receiving FVIII for washout purposes.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified