E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
An inherited gender-related coagulation disorder in which affected males do not produce functional coagulation factor VIII (FVIII) in sufficient quantities to achieve satisfactory blood clotting. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018938 |
E.1.2 | Term | Haemophilia A (Factor VIII) |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the annualised total bleeding rate of individually tailored prophylaxis with the historical bleeding rate observed in patients having received on-demand treatment with Human-cl rhFVIII from study GENA-01 |
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E.2.2 | Secondary objectives of the trial |
1.To compare the annualised spontaneous bleeding rate of individually tailored prophylaxis with the historical bleeding rate observed in patients having received on-demand treatment with Human-clrhFVIII
2.To compare the annualised total bleeding rate in patients with 2x/week(or less) prophylaxis with the historical bleeding rate observed in patients having received on-demand treatment with Human-clrhFVIII
3.To assess the median prophylactic dosing interval
4.To assess the PK of Human-clrhFVIII in terms of FVIII:C
5.To assess the safety of Human-clrhFVIII
Additional Objectives
1.To assess the clinical efficacy of Human-clrhFVIII in the treatment of breakthrough bleeding episodes (BEs)
2.To assess the clinical efficacy of Human-clrhFVIII in surgical prophylaxis
3.To assess the correlation of VWF antigen concentration and half-life of Human-clrhFVIII
4.To assess the association between ABO blood type and half-life of Human-cl rhFVIII
5.To assess Human-cl rhFVIII consumption data |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(a) Severe haemophilia A (FVIII:C < 1%) according to medical history
(b) Male patients ≥ 18 years of age
(c) Previous treatment with a FVIII concentrate (regular prophylaxis with good compliance or on-demand treatment) for at least 150 EDs
(d) Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start
(e) Immunocompetence (CD4+ count > 200/μL)
(f) Freely given written informed consent |
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E.4 | Principal exclusion criteria |
(a) Any coagulation disorder other than haemophilia A
(b) Present or past FVIII inhibitor activity (≥ 0.6 BU) according to medical history
(c) Severe liver or kidney disease (ALT and AST levels > 5 times of upper limit of normal, creatinine > 120 μmol/L)
(d) Treatment with any investigational medicinal product (IMP) except FVIII IMP within 14 days prior to the screening visit |
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E.5 End points |
E.5.1 | Primary end point(s) |
Reduction of the annualised total bleeding rate observed in the GENA-01 study (58.1 total bleeding episodes per patient per year) by 50% during individually tailored prophylaxis |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During individually tailored prophylaxis phase |
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E.5.2 | Secondary end point(s) |
1.Reduction of the annualised spontaneous bleeding rate observed in the GENA-01 study (38.5 spontaneous bleeding episodes per patient per year) by 50% during individually tailored prophylaxis
2. Reduction of the annualised bleeding rate observed in GENA-01 by 50% in patients with 2x/week prophylaxis or less
3. Median prophylactic dosing interval during individually tailored prophylaxis
4. Safety and tolerability of Human-cl rhFVIII by monitoring adverse events (AEs) throughout the study
|
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Secondary End Points 1-3 - During individually tailored prophylaxis phase
Secondary End Point 4 - 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 | 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 | 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) | No |
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.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 7 |
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 | No |
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 |
Canada |
Finland |
France |
Netherlands |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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
|
LVLS (in case more than 3 patients develop a neutralizing antibody (inhibitor) to Human-cl rhFVIII, the study will be stopped) |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |