|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Duchenne Muscular Dystrophy (DMD)
|Medical condition in easily understood language
|DMD is a genetic disease characterised by rapidly progressive muscle weakness and wasting which leads to severe disability
|Diseases [C] - Musculoskeletal Diseases [C05]
|E.1.2 Medical condition or disease under investigation
|Duchenne muscular dystrophy
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
| To assess the efficacy of idebenone compared to placebo, in delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by changes in Forced Vital Capacity percent predicted (FVC %p) using clinic-based spirometry
|Secondary objectives of the trial
| To assess the efficacy of idebenone compared to placebo in delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by:
Changes in Peak Expiratory Flow percent predicted (PEF %p) using clinic-based spirometry
Time to loss of 10% of Baseline Forced Vital Capacity (FVC) using clinic-based spirometry
To assess the efficacy of idebenone compared to placebo in delaying the loss of inspiratory muscle function as measured by changes in Inspiratory Flow Reserve (IFR) using clinic-based spirometry
- To assess the time to clinically relevant events and disease
|Trial contains a sub-study
|Principal inclusion criteria
|1. Male patients with a 35% ≤ FVC ≤ 80% of predicted value at Screening and at Baseline and who, in the opinion of the investigator are in the respiratory function decline phase.
2. Minimum 10 years old at Screening.
3. Signed and dated Informed Consent Form.
4. Documented diagnosis of DMD (severe dystrophinopathy) and clinical features consistent of typical DMD at diagnosis (i.e. documented delayed motor skills and muscle weakness by age 5 years). DMD should be confirmed by mutation analysis in the dystrophin gene or by substantially reduced levels of dystrophin protein (i.e. absent or <5% of normal) on Western blot or immunostaining.
5. Chronic use of systemic glucocorticoid steroids for DMD related conditions continuously for at least 12 months prior to Baseline without any dose adjustments on a mg/kg basis in the last 6 months (only dose adjustment determined by weight changes are allowed).
6. Ability to provide reliable FVC values at Screening and Baseline, and reproducible within 15% (relative change) at Baseline compared to Screening.
7. Patients assessed by the Investigator as willing and able to comply with the requirements of the study, possess the required cognitive abilities and are able to swallow study medication.
8. Patients who prior to screening have been immunized with 23-valent pneumococcal polysaccharide vaccine or any other pneumococcal polysaccharide vaccine as per national recommendations, as well as annually immunized with inactivated influenza vaccine.
|Principal exclusion criteria
|1. Symptomatic heart failure (defined as patients with structural heart disease, dyspnea, fatigue and impaired tolerance to exercise; Stage C by the ACCF/AHA guideline or NYHA Classes III-IV) and/or symptomatic ventricular arrhythmias.
2. Ongoing participation in any other therapeutic trial and/or intake of any investigational drug within 90 days prior to Baseline (only exception allowed is use of Deflazacort in the US as part of the Expanded Access Program or any corticosteroid product in trial for regimen optimization, for which the patient met the inclusion criterion 5)
3. Ongoing exon-skipping therapy or read-through gene therapy for DMD; previous exon-skipping or read-through gene therapy is allowed if the stop date was more than 6 months prior to Screening.
4. Planned or expected spinal fixation surgery during the study period (as judged by the Investigator, i.e. due to rapidly progressing scoliosis), prior spinal fixation surgery is allowed if it took place more than 6 months prior to Screening.
5. Asthma, bronchitis/COPD, bronchiectasis, emphysema, pneumonia or presence of any other non-DMD respiratory illness that affects respiratory function.
6. Chronic use of beta2-agonists or any use of other bronchodilating/bronchoconstricting medication (inhaled steroids, sympathomimetics, anti-cholinergics, antihistamines); chronic use is defined as a daily intake for more than 14 days.
7. Any bronchopulmonary illness that required treatment with antibiotics within 3 months prior to Screening.
8. Moderate or severe hepatic impairment as assessed and documented by the investigator (Liver function tests LFT, medical history or, when the parameters of the formula are available to site (see Appendix B), (use as guidance Child-Pugh class B [7 to 9 points] or Child- Pugh class C [10 to 15 points] could be indicative of such conditions) or severe renal impairment (eGFR <30 mL/min/1.73 m2).
9. Prior or ongoing medical condition or laboratory abnormality which in the Investigator’s opinion may put the patient at significant risk, may confound the study results or may interfere significantly with the patient’s participation in the study .
10. History of or current drug or alcohol abuse or use of any tobacco/marijuana products/smoking.
11. Known individual hypersensitivity to idebenone or to any of the ingredients/excipients of the study medication.
12. Daytime ventilator assistance (defined as use of any assisted ventilation while awake).
|E.5 End points
|Primary end point(s)
|The change from Baseline to Week 78 (or slope of changes over 78
weeks) in FVC %p assessed by clinic-based spirometry measurements.
The change from Baseline to Week 78 is considered the primary endpoint
for the FDA and the slope of changes over 78 weeks is considered the
primary endpoint for the EMA. The same principle applies for the
|Timepoint(s) of evaluation of this end point
|Secondary end point(s)
|The secondary endpoints will be evaluated in the following order in a
1. Rate of bronchopulmonary adverse events
2. The time to first 10% decline in FVC %p during the 78-week
treatment period, assessed by clinic-based spirometry measurements
3. The change from Baseline to Week 78 (or slope of changes over 78
weeks) in PEF %p assessed by clinic-based spirometry measurements
4. Rate of use of antibiotics
5. Proportion of patients with hospitalizations due to respiratory causes
6. The change from Baseline to Week 78 (or slope of changes over 78
weeks) in IFR assessed by clinic-based spirometry measurements
|Timepoint(s) of evaluation of this end point
|Secondary endpoint 1: 78 weeks
Secondary endpoint 2: 13, 26, 39, 52, 65 and 78 weeks
Secondary endpoint 3: 78 weeks
Secondary endpoint 4: 78 weeks
Secondary endpoint 5: 78 weeks
Secondary endpoint 6: 78 weeks
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
|Number of treatment arms in the trial
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial months