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 | 8.1 |
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 | No |
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 frequency of all bleeds compared to once-a-week prophylaxis regimen and to on-demand treatment (OD) with rFVIII-FS in WFI (Kogenate Bayer). |
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E.2.2 | Secondary objectives of the trial |
The main secondary objective is to evaluate the effect of a once-a-week prophylaxis regimen with BAY 79-4980 on the frequency of spontaneous bleeds (e.g joints, muscle) compared to once-a-week prophylaxis regimen and on-demand treatment (OD) with rFVIII-FS-WFI (Kogenate Bayer). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Males aged 12 to 70 years • Severe hemophilia A (< 1% FVIII:C) • 150 ED with any FVIII, > 20 ED during last year • On-demand treatment for the past year (Subjects having received isolated courses of prophylaxis for 6 consecutive weeks or less in a maximum of 2 occasions in the previous 12 months are also eligible) • At least 20 documented bleeds during the last 12 months (Or equivalent annualized bleeding frequency in no less than the previous 6 months, or documented corresponding infusions > 4 days apart, or if the treating physician confirms this bleeding frequency and this information is documented in the subjects medical records or a combination of them). • No current evidence of inhibitor antibody measured using the Nijmegen modified Bethesda assay (<0.6 BU/mL) 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 and measured by Nijmegen. Second sample –confirmatory- must in all cases be performed by the central lab. If a first recent sample is not available then 2 negative samples by 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. • No history of FVIII inhibitor antibody formation. (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] thereafter are also eligible) • Written informed consent by subject and parent / legal representative, if < 18 years
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E.4 | Principal exclusion criteria |
• Individuals with von Willebrand disease • Any individual with thrombocytopenia (platelets < 100 000/mm3) • Any individual with abnormal renal function (serum creatinine > 2.0 mg/dL) • Any individual with active hepatic disease (AST or ALT > 5xULN) • Any individual on treatment with immunomodulatory agents within the last 3 months prior to study entry or during the study. (the following drugs are allowed: alpha interferon 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) • Any individual with (HIV, HCV or due to another suspicious condition) an absolute CD4 lymphocyte cell count < 250 cells/mm3 • Individuals with positive Lupus Anticoagulant antibodies • Any individual with known hypersensitivity to the active substance, mouse or hamster protein, liposomes or PEG • Any individual who was receiving or had received other experimental drugs within 3 months prior to study entry • Any individual who required any pre-medication for FVIII infusions (e.g. anti-histamines) • Any individual with hypertension (diastolic blood pressure > 100 mmHg) which is uncontrollable with proper medication • Any individual with known unstable coronary artery angina and/or with known history of myocardial infarction. • Any individual who is unwilling to comply with study visits or any of the possible treatment regimens (e.g. not willing to receive on-demand treatment for one year) • Planned major surgery (including orthopedic) during the study
• Planned radio-isotopic synovectomy during the study
• Any individual who is not suitable for participation in this study for any reason, according to the Investigator
• Only for subjects participating in the PK substudy:
o Any individual receiving any pegylated medication (i.e. PEG interferon) in th e month prior to the PK session o Any subject not willing to or able to comply with fasting requirements (from 10pm previous night until 6 hours post infusion)
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable will be the number of all bleeds (spontaneous and trauma) occurring during 49 weeks of active treatments excluding the cumulative 10 weeks of placebo treatment |
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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 | No |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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 | Yes |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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 |
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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 | 10 |
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 | 10 |