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 |
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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 | 14.0 |
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 | 10010331 - Congenital, familial and genetic disorders |
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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 determine the long-term immunogenicity and tolerability of Human-cl rhFVIII in previously treated children with severe Haemophilia A. |
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E.2.2 | Secondary objectives of the trial |
To determine the long-term efficacy of Human-cl rhFVIII in the prophylaxis and in the treatment of (breakthrough) BEs, and in surgical prophylaxis in previously treated children with severe Haemophilia A. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Evaluable completion of study GENA-03 by having a study participation period of 6 months, provided that prophylaxis with Human-cl rhFVIII is continued without intermediate interruption.
2. Voluntarily given, fully informed written and signed consent obtained from the parents (or legal guardians) before any study-related procedures are conducted. The need for obtaining assent will depend on the subjects’ developmental stage and intellectual capacity.
3. Capability to understand and comply with the relevant aspects of the study.
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E.4 | Principal exclusion criteria |
1. Development of FVIII inhibitors (≥0.6 Bethesda units [BU]) in the course of study GENA-03.
2. Any severe liver or kidney disease (alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels >5 times of upper limit of normal, creatinine >120 µmol/L).
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E.5 End points |
E.5.1 | Primary end point(s) |
Long-term immunogenicity and tolerability are the primary endpoints of the study. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Inhibitor activity will be determined at tri-monthly intervals until study completion. Simultaneously, anti-rhFVIII antibodies will be measured. The same parameters will also be determined in case an inhibitor development is suspected. The sampling for inhibitor and antibody measurements should be performed not less than 48 hours after the previous administration of any FVIII product. In the case of positive inhibitor results, an inhibitor retesting using a second separately drawn sample should be performed.
Long-term clinical tolerability will be assessed by monitoring Adverse Events (AEs) throughout the entire study duration.
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E.5.2 | Secondary end point(s) |
1. Long-Term Efficacy of Prophylactical Treatment
2. Long-Term Efficacy of Treatment of Bleeding Episodes
3. Efficacy in Surgical Prophylaxis |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Efficacy is to be assessed by evaluating the frequency of IMP injections, and to the prophylactic IMP doses needed. The number of spontaneous breakthrough BEs will be evaluated. Overall study drug consumption data (FVIII [IU/kg]), per month and per year), per subject and in total, will be analysed.
2. Efficacy is to be assessed by the subject/subject’s parents (or legal guardians) at the end of a BE (in collaboration with the Investigator in case of on-site treatment).
3. Efficacy will be assessed by the surgeon at the end of surgery (i.e. after last suture), as well as postoperatively (i.e. at date of discharge or on postoperative Day 6, whichever occurs later) by both the surgeon and the haematologist. |
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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 | No |
E.8.1.2 | Open | No |
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.8.3 |
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 | 13 |
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 |
Russian Federation |
Turkey |
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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
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Once the patient has completed the study, the IMP is commercially available, and treatment with human-cl rhFVIII can be continued. The decision on the treatment is the responsibility of the treating physician.
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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 | 3 |
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 | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |