E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne Muscular Dystrophy |
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E.1.1.1 | Medical condition in easily understood language |
Duchenne Muscular Dystrophy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
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 |
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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 |
We want to test whether is possible to prepare genetically corrected cells from DMD patients and administer the cells to few muscles of the same patients to verify how much dystrophin is produced. We want to test whether the treatment is safe. |
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E.2.2 | Secondary objectives of the trial |
In case of positive results (i.e. dystrophin produced at 10% or more of the level of a healthy muscle) we want to know whether this is sufficient to improve/stabilise the force of contraction of the thumb. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Age between 12 and 16 years at time of study entry, provided that participants matching the eligibility criteria can be identified. Otherwise patients of progressively younger age may be recruited up to a minimum age of 8 years. 2. Non-ambulant at the time of recruitment. 3. Confirmed diagnosis of DMD with documented exon 51 skippable mutations in dystrophin gene. 4. Progression of muscle degeneration ≤ to 50% reduction of muscle mass as determined by quantitative MRI (grade 2: Kinali et al. 2011). 5. Written informed consent of caregivers of DMD patients and patient’s assent. |
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E.4 | Principal exclusion criteria |
1. Positive hepatitis B surface antigen, hepatitis C antibody test, or human immunodeficiency virus (HIV) test. 2. Presence of immune deficiency, neoplastic or autoimmune disease (based on clinical history). 3. Bleeding disorder. 4. Any known allergies to products likely to be used in the study. 5. Prior or ongoing medical condition (e.g. concomitant illness, psychiatric condition, behavioural disorder, drug abuse), medical history, physical findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject, making it unlikely that the course of treatment or follow-up would be completed, or could impair the assessment of study results. 6. Ongoing participation in any other therapeutic clinical trial or treatment with exon skipping oligonucleotides. Use of steroids is considered standard care, as well as concomitant medications (e.g. B blockers, ACEI, ARBs, vitamin D, bisphosphonates) and therefore permitted. 7. FS (fraction shortening) < 28% or ECG finding significant for underlying cardiac impairment. 8. Pulmonary function tests assessed by spirometry (if cooperative) of FEV1 and FVC <30% of the predicted values. If unable, pulse oximetry < 95 % in room air. 9. Change of medication related to DMD within last 3 months with the exception of adjustment based on weight gain of current medications. 10. Presence of severe scoliosis (curve >50°). 11. Presence of significant impairment of renal or hepatic function. |
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E.5 End points |
E.5.1 | Primary end point(s) |
We will test safety of treatment and efficacy in restoring synthesis of dystrophin in the injected muscle.
Safety: To assess the incidence of adverse events (any grade) in DMD patients treated with intra muscular foot injections of auto-MABS after genetic correction with a lentiviral vector expressing a small nuclear RNA engineered to skip exon 51 of the dystrophin gene. Note: In vitro/in vivo pre-clinical safety assessments will be performed on IMP prior to injection, as described in the IMPD.
Efficacy: To determine cell engraftment and dystrophin expression after a single intramuscular injection into the foot medial Extensor Digitorum Brevis (EDB) of genetically corrected auto-MABS. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Monitoring for SAE will be carried out throughout the trial. Evaluation of dystrophin expression will be carried out three months after IMP injection. |
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E.5.2 | Secondary end point(s) |
Safety: Incidence and severity of local and systemic adverse events (any grade) in DMD patients treated with intramuscular injections of genetically corrected auto-MABS for one year from the injection.
Efficacy: Enhancement, stabilization or decrease of the thumb muscle strength in DMD patients treated with injections of genetically corrected auto-MABS, evaluated periodically (starting at recruitment) up to 1 year from the last injection and in comparison with contralateral non injected thumb. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Evaluation will be carried out throughout the trial. |
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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 | No |
E.6.3 | Therapy | No |
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) | 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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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) | 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.8.3 |
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 | No |
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
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The end of the trial is tentatively planned after the final visit of the last patient (12-18 months after the last patient receives the foot injection). In case of a SAE, linked to the trial, the trial may end prematurely. On the other hand, should the clinical benefit persist up to completion, a new observational study may be planned to monitor the force of contraction of the transplanted hand until it remains constant (± 10 % of the average values recorded in the previous years). |
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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 | |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 28 |