Duchenne Muscular Dystrophy (DMD) MedDRA version: 20.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Santhera Pharmaceuticals (Switzerland) Limited
Eligibility
Sex/Gender
Male
Inclusion criteria
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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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 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), 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 <30mL/min/1.73m2). 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).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: 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 time to clinically relevant events and disease milestones ? 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;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 secondary endpoints.;Timepoint(s) of evaluation of this end point: 78 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints will be evaluated in the following order in a hierarchical manner: 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 | — |
Countries
Austria, Belgium, Bulgaria, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States
Contacts
Public ContactQuentin Desvigne
Santhera Pharmaceuticals (Switzerland) Limited
Outcome results
None listed