E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe haemophilia A (FVIII:C less than or equal to 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 |
|
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 preventative treatment with a new Factor VIII concentrate (human-cl rhFVIII), in the treatment of bleeding episodes and in the control of bleeding during planned surgery. |
|
E.2.2 | Secondary objectives of the trial |
The secondary aims of the study are:
- To calculate the recovery of Factor VIII (by measuring the clotting activity before and after administering human-cl rhFVIII)
- To investigate whether the new treatment provokes an immune response in the body
- To assess the safety of human-cl rhFVIII |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
In order to qualify for study enrolment, each subject must satisfy the following criteria before
study entry.
1. Must have severe haemophilia A (FVIII:C less than or equal to 1%).
2. Male subjects 12 years of age and above.
3. Previously treated with FVIII concentrate, at least 150 EDs.
4. Immunocompetent (CD4+ count above >200/µL).
5. Negative for anti-HIV; if positive, respective viral load <200 particles/µL.
6. Freely given written informed consent. |
|
E.4 | Principal exclusion criteria |
Subjects will not be included if any of the following exclusion criteria are met.
1. Other coagulation disorder than haemophilia A.
2. Present or past FVIII inhibitor activity (greater than or equal to 0.6 BU).
3. Severe liver or kidney disease (ALAT and ASAT levels >5 times of upper limit of normal, creatinine >120 µmol/L).
4. 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.
5. Participation in another interventional clinical study currently or during the past month.
6. Participation in any other study with human-cl rhFVIII. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the efficacy of human-cl rhFVIII in:
- Prophylactic Treatment
- On-Demand Treatment of Bleeding Episodes
- Surgical Prophylaxis |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
end of the study at 6 months |
|
E.5.2 | Secondary end point(s) |
Secondary endpoints are:
- Calculate the incremental recorvery of FVIII:C for human-cl rhFVIII.
- Investigate the immunogenic potential of human-cl rhFVIII.
- Assess the safety of human-cl rhFVIII.
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Recovery: Will be determined for each patient at the beginning of the study, after 3 months and at study completion after 6 months.
Immunogenic potential: Inhibitor activity and anti-rhFVIII antibodies will be determined at screening, prior to the first and second infusion of human-cl rhFVIII, after 10 to 15 EDs, and prior to infusion human-cl rhFVIII at the 3-month and 6-month visit.
Safety: Will be assessed by monitoring vital signs, routine laboratory parameters at screening, on the day of first infusion, and after 3 and 6 months (completion visit), and by monitoring adverse events throughout the study.
|
|
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 | 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 | No |
E.8.1.1 | Randomised | No |
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 | No |
E.8.1.7 | Other | No |
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.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 5 |
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 | No |
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 | 11 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |