E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe haemophilia A (FVIII:C <1%) |
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MedDRA Classification |
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 |
To determine in previously treated subjects suffering from severe haemophilia A the efficacy of human-cl rhFVIII during prophylactic treatment, in the treatment of bleeding episodes and in surgical prophylaxis. |
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E.2.2 | Secondary objectives of the trial |
To calculate the incremental recovery of FVIII:C for human-cl rhFVIII.· To investigate the immunogenic potential of human-cl rhFVIII.· To assess the safety of human-cl rhFVIII. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Severe haemophilia A (FVIII:C less/equal 1%).· Male subjects greater/equal 12 years of age.· Previously treated with FVIII concentrate, at least 150 EDs.· Immunocompetent (CD4+ count >200/µL).· Negative for anti-HIV; if positive, viral load <200 particles/µL or <400,000 copies/mL. Freely given written informed consent. |
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E.4 | Principal exclusion criteria |
Other coagulation disorder than haemophilia A.· Present or past FVIII inhibitor activity (>0.6 BU).· Severe liver or kidney disease (ALAT and ASAT levels >5 times of upper limit of normal, creatinine >120 µmol/L).· Receiving or scheduled to receive immuno-modulating drugs (other than anti-retroviral chemotherapy) such as alpha-interferon, prednisone (equivalent to >10 mg/day), or similar drugs.· Participation in another interventional clinical study currently or during the past month. · Participation in any other study with human-cl rhFVIII. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: Prophylactic treatments: · Overall efficacy assessment after a total of at least 50 EDs per subject at the end of the study at 6 months.· The frequency of bleeds under prophylactic treatment will be calculated. Study drug consumption data (FVIII IU/kg per month, per year) per subject and in total will be evaluated.
The following parameters will be documented in addition:· Dates and times of study product infusions.· Details of dose(s) and product batch numbers used for prophylactic treatment (in IU).· Details of BEs (if any) occurring under prophylactic treatment.
Bleeding episodes: Efficacy assessment of each IMP infusion and an overall efficacy assessment at the end of the BE.
The following parameters have to be documented in addition:· Type, site, severity of bleeding.· Start/end date and time of BE.· Dates and times of study product infusions.·
Details of dose(s) and batch number used to treat BE- increased and decreased doses of human-cl rhFVIII used to treat individual bleeding episodes (frequency and relative magnitude of dose changes)- changes in the doses per infusion and changes in the total dose used to treat subsequent bleeding episodes of the same type (e.g. elbow, knee, etc.) in the same patient (frequency and relative magnitude of dose changes).
Surgical prophylaxis:· Overall efficacy assessment (taking the intra- and post operative assessment into account) after the end of the surgical prophylactic treatment phase by the surgeon and haematologist.· Average and maximum expected estimated blood loss compared to the actual estimated blood loss.
The following parameters will be documented in addition:· Location, severity, and type (planned or emergency) of surgery.· Expected and actual duration of surgical procedure.· Details of administered dose(s) of human-cl rhFVIII given pre-, intra- and/or post-operatively including dates, times, and batch number.· Pre-, intra-, and post-operative FVIII plasma levels.· Details on concomitantly administered products.· A brief narrative describing the outcome of the intervention. |
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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 | Yes |
E.6.3 | Therapy | Yes |
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 | 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) | 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 | No |
E.8.1.1 | Randomised | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |