E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Duchenne Muscular Dystrophy (DMD), Becker Muscular Dystrophy (BMD) and symptomatic carriers for DMD or BMD |
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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 | 14.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10059117 |
E.1.2 | Term | Becker's muscular dystrophy |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10052655 |
E.1.2 | Term | Duchenne muscular dystrophy gene carrier |
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 | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the ability of CRD007 to decrease creatine kinase activity levels in subjects with DMD or BMD and in subjects being carriers for DMD or BMD |
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E.2.2 | Secondary objectives of the trial |
-To assess the ability of CRD007 to decrease the level of a range of other disease related biomarkers
-To assess the ability of CRD007 to improve the outcome of functional tests
-To assess the safety of CRD007
- To assess the safety margins of CRD007 in relation to plasma concentrations of pemirolast observed in clinical and toxicological studies |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1.Documented diagnosis of dystrophinopathy in the form of mutation analysis in the dystrophin gene
2.Clinically documented delayed motor skills and muscle weakness
3.Prior documented elevated creatine kinase (>5 x ULN)
4.Age <12 years (females in the pre-pubertal stage as defined by Tanner criterion I)
5.Body weight ≥14 kg
6.Informed assent from subject before any trial related activity is carried out
7.Written informed consent obtained from parent(s) / legal guardian(s) before any trial related activity is carried out
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E.4 | Principal exclusion criteria |
1.Severe functional impairment (e.g. non-walkers) resulting in inability to perform meaningful repeated assessment of functional capabilities, according to the investigator’s judgment
2.Moderate or severe hepatic impairment or severe renal impairment, according to the investigator’s judgment
3.Prior or ongoing medical condition or laboratory abnormality that in the investigator’s opinion could adversely affect the safety of the subject.
4.Subject or parent(s) / legal guardian(s) not willing and able to comply with the requirements of the study
5.Subject not able to follow trial procedures, according to the investigator’s judgement
6.Known individual hypersensitivity to any of the ingredients/excipients of the study medication (see Section 7.1.1)
7. Applicable for part B, only: Systemic glucocorticoid therapy within 30 days prior to start of IMP treatment
8.Planned systemic glucocorticoid therapy during the trial period
9.Previous exposure to idebenone
10.Participation in any other therapeutic trial and/or intake of any investigational drug within 90 days prior to Visit 1
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E.5 End points |
E.5.1 | Primary end point(s) |
The relative change in creatine kinase from enrolment (Visit 1) to 12 weeks of treatment
(Visit 5)
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From enrolment (Visit 1) to 12 weeks of treatment (Visit 5)
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E.5.2 | Secondary end point(s) |
•The relative change in other disease related biomarkers between baseline and 12 weeks of treatment
a. Myoglobin
b. miR-1, miR-133, miR-206
•The relative change in the total North Star Ambulatory Assessment score
•The relative change in the time needed to perform "Rise from floor", "Run (10 m)", "Climb 4 steps"
Change in safety related assessments between baseline and 12 weeks
a. Blood pressure (diastolic and systolic) and pulse
b. Electrocardiogram
c. Biochemistry laboratory values
d. Hematology laboratory values
•Incidence of adverse events by type and severity
•Cpl(CRD007) and derived pharmacokinetic parameters |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Myoglobin: at baseline and 12 weeks of treatment
•miR-1, miR-133, miR-206:at baseline and 12 weeks of treatment
•The relative change in the total North Star Ambulatory Assessment score:at baseline and 12 weeks of treatment
•The relative change in the time needed to perform "Rise from floor", "Run (10 m)", "Climb 4 steps": at baseline and 12 weeks of treatment
•Change in safety related assessments : at baseline, after 6 and 12 weeks of treatment
•Incidence of adverse events: at baseline and once every week and 2 weeks after end of treatment
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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 | 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) | 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 | 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.8.3 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
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 | 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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The end of trial is defined as the date of last subject last visit. |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |