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 |
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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 | 17.1 |
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 |
Core study: To preliminarily assess the effect of PRO051 at different dose levels in patients with DMD. To assess the safety and tolerability of PRO051 at different dose levels in patients with DMD. To determine the pharmacokinetics of PRO051 at different dose levels after SC administration in patients with DMD. Administration of PRO051 beyond the core study period (SC administration): To assess the effect of PRO051 after SC administration at 6 mg/kg or capped at 300 mg in patients with DMD. To assess the safety and tolerability of PRO051 after SC at 6 mg/kg or capped at 300 mg in patients with DMD. To determine the pharmacokinetics of PRO051 after SC administration at 6 mg/kg in patients with DMD. Administration of PRO051 beyond the core study period (IV administration): IV dosing will be investigated as an alternative route of administration: Please refer to page no.25 of protocol. |
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E.2.2 | Secondary objectives of the trial |
To determine the pharmacokinetics of PRO051 at different dose levels after subcutaneous administration in patients with Duchenne muscular dystrophy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Boys aged between 5 and 16 years inclusive 2. Duchenne muscular dystrophy resulting from a mutation correctable by treatment with PRO051 3. Not ventilator dependent 4. Life expectancy of at least 6 months 5. No previous treatment with investigational medicinal treatment within 6 months prior to the study 6. Willing and able to adhere to the study visit schedule and other protocol requirements. 7. Written informed consent signed (by parent(s)/legal guardian and/or the patient, according to the local regulations). |
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E.4 | Principal exclusion criteria |
1. Aberrant RNA splicing and/or aberrant response to PRO051, detected by in vitro PRO051 assay during screening. 2. Known presence of dystrophin in ≥ 5% of fibres in a pre-study diagnostic muscle biopsy 3. Severe muscle abnormalities defined as increased signal intensity in >50% of the tibialis anterior muscle at MRI 4. FEV1 and/or FVC < 60% of predicted 5. Current or history of liver or renal disease 6. Acute illness within 4 weeks prior to treatment (Day 0) which may interfere with the measurements 7. Severe mental retardation which in the opinion of the investigator prohibits participation in this study 8. Severe cardiac myopathy which in the opinion of the investigator prohibits participation in this study 9. Need for mechanical ventilation 10. Creatinine concentration above 1.5 times the upper limit of normal (age corrected) 11. Serum ASAT and/or ALAT concentration(s) which suggest hepatic impairment 12. Use of anticoagulants, antithrombotics or antiplatelet agents 13. Subject has donated blood less than 90 days before the start of the study 14. Current or history of drug and/or alcohol abuse 15. Participation in another trial with an investigational product |
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E.5 End points |
E.5.1 | Primary end point(s) |
Effect parameters • Dystrophin expression in muscle biopsy • Exon skip efficiency (RT-PCR on dystrophin mRNA from muscle biopsy and mononuclear blood cells) • Muscle function (timed tests and 6-minutes walk) • Muscle strength (QMT, MMT, handheld myometry, spirometry)
Safety • Frequency and number of adverse events • Local tolerability • Complement activation (complement split products C3a, C5a, Bb) • Coagulation (aPTT) • Cytokines (IL-6, TNF-a) and chemokine (MCP-1) • Immune response to dystrophin (antibodies) • ECG, heart rate and blood pressure • Safety haematology and biochemistry parameters • Urinalysis |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
See Table 4-14 in protocol: schedule of assesments |
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E.5.2 | Secondary end point(s) |
Pharmacokinetic parameters • t1/2 • AUC: 0-24h, 2hh-7d, 0-∞ • Cmax, Ctrough 7d • tmax • distribution volume • clearance |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
See Table 4-14 in protocol: schedule of assesments |
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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 | 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 | 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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
dose escalation followed by continued treatment |
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E.7.2 | Therapeutic exploratory (Phase II) | Yes |
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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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.8.2.4 | 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 | 2 |
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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Last visit of last subject |
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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 | 7 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 7 |
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 |