E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne Muscular Dystrophy |
|
E.1.1.1 | Medical condition in easily understood language |
|
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10013801 |
E.1.2 | Term | Duchenne muscular dystrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
|
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 |
A phase I/II/III study consisting of 3 parts: - Part 1: To determine the dose of IMP: a safe and tolerable dose with acceptable gene expression, to carry over to part 2. - Part 2: To demonstrate clinical efficacy of IMP vs placebo at 1 year after inclusion. To assess the safety and tolerability of IMP vs placebo at 1 year after inclusion. - Part 3. To assess the safety and tolerability of IMP |
|
E.2.2 | Secondary objectives of the trial |
- To assess the biodistribution of IMP - To demonstrate the pharmacodynamic activity of IMP - To assess the immunogenicity of IMP - To compare the efficacy on the disease course after 2 years after inclusion, between patients treated with active IMP at first and patients treated after a delay of one year |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 Male 2 Being included in the GNT-014-MDYF study 3 6 to 10 years (inclusive) 4 Positive gene testing with detailed genotyping confirmation of DMD, ie DMD mutations expected to abolish the production of dystrophin |
|
E.4 | Principal exclusion criteria |
1 Presence of neutralizing antibodies against AAV8 2 Cardiomyopathy based on physical/cardiological examination and echocardiography with Left Ventricular Ejection Fraction (LVEF) below 55% and/or fractional shortening (SF) below 28% 3 Any respiratory assistance needed including non-invasive daytime or nocturnal ventilation 4 Inability to perform the planned respiratory functions tests |
|
E.5 End points |
E.5.1 | Primary end point(s) |
NSAA: change from baseline at week 52 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
- Safety and tolerability, measured by the incidence of adverse event (AE) or serious adverse event (SAE) evaluated by changes in laboratory parameters, vital signs and in the physical examination - PK/PD endpoints including vector shedding quantification in blood, urine, saliva, feces - Clinical efficacy endpoints including NSAA, Time to 10 Meters Walk/Run Test (10MWRT), Time to Rise From Floor (RFF), 6-Minutes Walk Test (6MWT)
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
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) | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
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 |
France |
Israel |
United Kingdom |
United States |
|
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
|
Last patient last visit (LPLV) of the 5 years safety follow up period after IMP infusion. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 8 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 8 |