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

• Conditions: Hemophilia A; MedDRA version: 9.1Level: LLTClassification code 10060613Term: Hemophilia A (Factor VIII); MedDRA version: 9.1Level: LLTClassification code 10018937Term: Haemophilia A

• Registration Number: EUCTR2007-003718-32-BE
• Lead Sponsor: Bayer HealthCare AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2008-01-04
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Male
• Target Recruitment: 100

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 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.
Subjects with no history of FVIII inhibitor antibody formation. (=0.6BU/mL using the Nijmegen-modified Bethesda assay)
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 elevated LDL- and total cholesterol profile according to AHA-ATP recommendations 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. Subjects may have water only. Food intake on the day of injection should be documented.

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 within last 5 years prior to enrollment (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. anti-histamines)
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.