E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe haemophilia A (FVIII:C <=1%) |
|
E.1.1.1 | Medical condition in easily understood language |
Blood coagulation factor VIII disorder |
|
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 | 13.1 |
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 human-cl rhFVIII during prophylactic treatment, in the treatment of bleeding episodes and in surgical prophylaxis. |
|
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. |
|
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. |
|
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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
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.
Treatment of bleeding episodes:
The proportion of bleeding episodes successfully treated with human-cl rhFVIII will be evaluated for all BEs as well as for BEs of different severity. “Successfully treated” are all “excellent” and “good” efficacy ratings of treated BEs.
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. |
|
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) |
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 | 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 | No |
E.8.1.2 | Open | Information not present in EudraCT |
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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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
|
|
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 | 5 |
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 |