E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060613 |
E.1.2 | Term | Hemophilia A (Factor VIII) |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018937 |
E.1.2 | Term | Haemophilia A |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
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. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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 the 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
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E.5 End points |
E.5.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
without comparator in follow-up phase |
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E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 36 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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is provided in the protocol (see visit 11) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |