E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe hemophilia A (FVIII:C <1%) |
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E.1.1.1 | Medical condition in easily understood language |
Blood coagulation factor VIII disorder |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018937 |
E.1.2 | Term | Haemophilia A |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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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 |
To determine the pharmacokinetics of human-cl rhFVIII in terms of the FVIII coagulant activity (FVIII:C) and to compare it with the licensed FVIII concentrate Kogenate/Helixate in previously treated subjects suffering from severe hemophilia A. |
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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 clinical efficacy and safety of human-cl rhFVIII in the treatment of bleeding episodes (BE). To assess clinical efficacy and safety of human-cl rhFVIII in surgical prophylaxis. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Must have severe hemophilia A (FVIII:C <1%).
Male subjects greater/equal 12 and less or equal than 65 years of age.
Body weight 25 kg to 110 kg.
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 hemophilia A.
Present or past FVIII inhibitor activity (>0.6 BU).
Severe liver or kidney disease (ALT and AST 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare the AUC of human-cl rhFVIII and Kogenate/Helixate for FVIII:C (normalized for the administered dose) using both the chromogenic (CHR) and the one-stage (OS) assay and the actual potency of human-cl rhFVIII and Kogenate/Helixate. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after pharmacokinetic cycle 2. |
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E.5.2 | Secondary end point(s) |
- To calculate the incremental recovery of FVIII:C for human-cl rhFVIII
- To investigate the immunogenic potential of human-cl rhFVIII
- To assess clinical efficacy and safety of human-cl rhFVIII in the treatment of bleeding episodes (BE)
- To assess clinical efficacy and safety of human-cl rhFVIII in surgical prophylaxis. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Recovery: Will be determined for each patient at study entry and after 3 and 6 months of treatment.
Immunogenic potential: Inhibitor activity and anti-rhFVIII antibodies will be determined at study entry, immediately before both pharmacokinetic cycles, in the 48 hour sample of both pharmacokinetic cycles, after 10 to 15 exposure days with human-cl rhFVIII, at the 3-month visit and every 3 months until study completion.
Safety: Will be assessed by monitoring vital signs, routine laboratory parameters at screening, at both pharmacokinetic cycles, at the 3-month and 6-month visits and at the study completion visit, and by monitoring adverse events throughout the study. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | Yes |
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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | Yes |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 3 |
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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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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |