Randomized, active-controlled, double-blind, parallel design study to evaluate the efficacy and safety of a once-a-week prophylaxis treatment with BAY 79-4980 compared to three times-per-week prophylaxis with rFVIII-FS in previously treated patients with severe hemophilia A. - ND

• Conditions: Severe hemophilia A; MedDRA version: 9.1Level: LLTClassification code 10056493Term: Haemophilia A without inhibitors

• Registration Number: EUCTR2007-003718-32-IT
• Lead Sponsor: BAYER

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-07-02
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 250

Inclusion Criteria

-Males aged 12 to 70 years, inclusion of adolescent subjects will start after 20 adults have completed the run-in phase with acceptable tolerability and the DSMB has approved the start of recruitment of adolescent subjects -Subjects with severe hemophilia A (< 1% FVIII:C) -Subjects with equal or greater than 150 EDs with any FVIII in total -Subjects who have been on-demand treatment (no more than 40% of patients and at least 20% are high-frequency bleeders [≥20 bleeds/year]) with an average of minimum 1 relevant bleed per month or have been on secondary prophylaxis treatment with not more than a 3x/week schedule with the history of minimum 12 relevant bleeds per year prior to be on secondary prophylaxis treatment -Subjects with bleeding events and/or treatments during the last 6 months prior to study entry which are documented in the subjects medical records. -Subjects with no measurable inhibitor activity using the Nijmegen-modified Bethesda assay (>0.6BU/mL is considered positive) in two 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 sample -confirmatory- must in all cases be performed by the central lab using the Nijmegen test. If a first recent sample is not available then 2 negative samples by the central lab at least 1 week apart should be obtained). At least 3 days without receiving FVIII must have passed prior to collect samples for inhibitors; borderline cases will be excluded (values between ≥0.3 to <0.6 BU). -Subjects with no history of FVIII inhibitor antibody formation. (≥0.6BU/mL using the Nijmegen-modified Bethesda assay; subjects with a maximum historical titer of 1.0 BU in no more than one occasion with the Classical Bethesda assay but at least three successive negative [<0.6 BU] results thereafter are also eligible) -Subjects who complete an EPD (electronic patient diary) device training and demonstrate the ability to correctly use it -Written informed consent by subject and parent / legal representative, if < 18 years. Only for subjects who are participating in the lipid-profile: -Subjects with no abnormal LDL- and total cholesterol profile prior to study entry and not on lipid-lowering drugs -Subjects who are willing to or able to comply with fasting requirements -12 hours overnight fasting followed by additional 3 hours after injection. Subjects may have water only.
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) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

-Subjects who are receiving primary prophylaxis (start of prophylaxis before or directly after the first joint bleed without relevant interruptions) -Subjects on prophylaxis with documented requirements of > 75 IU/kg/week -Subjects with any other bleeding disease beside hemophilia A (i.e., von Willebrand disease) -Subjects with thrombocytopenia (platelets < 100,000/mm3) -Subjects with abnormal renal function (serum creatinine > 2.0 mg/dL) -Subjects with elevated hepatic transaminases (AST or ALT > 5xULN) -Subjects on treatment with immunomodulatory agents within the last 3 months prior to study entry or during the study (the following drugs are allowed: interferon-alpha-treatment for HCV, HAART therapy for HIV and/or a total of two courses of pulse treatment with steroids for a maximum of 7 days at 1mg/kg or less) -Subjects with an absolute CD4 lymphocyte cell count < 250 cells/mm3 -Subjects with positive Lupus Anticoagulant antibodies or history thereof -Subjects with known hypersensitivity to the active substance, mouse or hamster protein, liposomes or PEG -Subjects with severe dyslipidemia of all causes LDL-C ≥ 190 mg/dl) -Subjects who are receiving or had received other experimental drugs within 3 months prior to study entry -Subjects who require any pre-medication for FVIII injections (e.g. antihistamines) -Subjects with uncontrollable hypertension (diastolic blood pressure > 100 mmHg) -Subjects with known unstable coronary artery angina and/or with known history of myocardial infarction. -Subjects who are unwilling to comply with study visits or the treatment regimens -Subjects who have planned major surgery (including orthopedic) or radioisotopic synovectomy during the study -Subjects who are not suitable for participation in this study for any reason, according to the Investigator Only for subjects who are participating in the PK sub-study: -Subjects who are receiving any pegylated medication (e.g. PEG interferon) in the month prior to the PK session.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective is to evaluate the effect of a once-a-week prophylaxis regimen with BAY 79-4980 on the protection from total bleeds compared to a three times-per-week prophylaxis regimen with rFVIII-FS.;Secondary Objective: The secondary objective is to evaluate the effect of a once-a-week prophylaxis regimen with BAY 79-4980 on the protection from joint bleeds compared to a three times-per-week prophylaxis regimen with rFVIII-FS.;Primary end point(s): The primary efficacy variable will be the percentage of subjects with less than 9 total bleeds per year. The three weeks run-in phase will not be considered for efficacy analyses.