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 |
Hemophilia A (Factor VIII deficiency) |
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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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060613 |
E.1.2 | Term | Hemophilia 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 demonstrate safety of GreenGene™ F with respect to inhibitor development (neutralizing anti-Factor VIII antibodies) and long-term safety •To evaluate the hemostatic efficacy in prophylaxis (rate of breakthrough bleeding) and on demand treatment in the management of acute bleeding events •To evaluate the physicians and subjects rating of response for on demand treatment of bleeding episodes; and •To evaluate peri-operative hemostatic control of GreenGene™ F during surgical and invasive diagnostic procedures. |
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E.2.2 | Secondary objectives of the trial |
Please see main objective above. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetic sub-study. This is described in the main clinical study Protocol. Objectives are: •To demonstrate pharmacokinetic (PK) profile of GreenGene™ F •To compare the PK profile of GreenGene™ F to an approved recombinant Factor VIII product (Refacto AF); and •To determine the PK parameters for GreenGene™ F after 50 exposure days in a cohort of subjects who participated in the initial PK analysis and compare these parameters to those recorded at the beginning of the study. |
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E.3 | Principal inclusion criteria |
1.Male or female subjects age ≥ 12 years at time of informed consent 2.Body weight ≥ 35 kg 3.Diagnosed with severe hemophilia A. Subjects must have severe hemophilia A with baseline FVIII < 1%, <0.01 IU/mL 4.Have ≥ 150 previous exposure days to FVIII concentrates, as documented in the subject's medical records 5.Subjects included in the on-demand treatment cohort must have a verifiable record of at least three bleeding episodes per month on average in the last 6 months prior to enrollment 6.Negative assays for FVIII inhibitor at inclusion(<0.6BU Nijmegen assay) 7.Negative assays for FVIII inhibitor in subject files(<0.6BU Nijmegen assay). No history of positive inhibitor is allowed |
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E.4 | Principal exclusion criteria |
1.Presence at Screening of FVIII inhibitor ≥ 0.6 BU as tested with the Nijmegen modification of the Bethesda assay in either central or local laboratory 2.History of FVIII inhibitor of ≥ 0.6 BU as measured using the Nijmegen modification of the Bethesda assay 3.History of FVIII inhibitor ≥ 1.0 BU if the subject has been tested routinely using the original Bethesda assay, or history of periods with low recovery and no response to Factor VIII treatment 4.Demonstrated an inability to respond to conventional doses of FVIII therapy 5.History of incremental recovery of Factor VIII <1.35% per IU/kg infused 6.Hematological disorders or blood coagulation diseases(e.g., idiopathic thrombocytopenic purpura, von Willebrand disease, etc.) other than haemophilia A 7.Laboratory or clinical evidence of portal vein hypertension including, but not limited to, an INR>1.4, the presence of splenomegaly and/or spider aniomata of physical examination and/or a history of esophageal hemorrhage or documented esophageal varices |
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety and efficacy; The primary safety objective is to demonstrate a sufficiently low incidence of inhibitor associated with the use GreenGene™ F. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Safety and efficacy; Following a minimum 50 exposure days for both prophylaxis and on demand patients |
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E.5.2 | Secondary end point(s) |
Safety and efficacy: • Frequency of breakthrough bleeds (total, trauma and joint); • Subject evaluation of efficacy; • Number of infusions per bleeding episodes; • Units of FVIII per infusion per bleeding episode; • Units of FVIII per bleeding; and • Units of FVIII per prophylaxis treatment. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Safety and efficacy; Following a minimum 50 exposure days for both prophylaxis and on demand patients. |
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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 | 3 |
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 | 23 |
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 |
Croatia |
Moldova, Republic of |
New Zealand |
Poland |
Romania |
Russian Federation |
Ukraine |
United Kingdom |
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
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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 | 4 |
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 |