Clinical trial: A Phase III Double-blind Study With Idebenone in Patients With Duchenne Muscular Dystrophy (DMD) Taking Glucocorticoid Steroids (NCT02814019)

Eligibility 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 <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 adjustments 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.

        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 approved
             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 fusion surgery during the study period (as judged by the
             Investigator; i.e. due to rapidly progressing scoliosis), previous spinal fusion
             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, anticholinergics, 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 (use as guidance Child-Pugh class B [7 to 9
             points] or Child-Pugh class C [10 to 15 points] - see Appendix B) or severe renal
             impairment (eGFR <30 mL/min/1.73 m2).

          9. Prior or ongoing medical condition or laboratory abnormality that 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. Relevant history of or current drug or alcohol abuse, or use of any tobacco or
             marijuana products/smoking.

         11. Known individual hypersensitivity to idebenone or to any of the ingredients or
             excipients of the study medication.

         12. Daytime ventilator assistance (defined as use of any assisted ventilation while
             awake).

        Note: Patients who suffer from a severe, unstable condition including (but not limited to)
        cancer, auto-immune diseases, hematological diseases, metabolic disorders or
        immunodeficiencies, and who are at risk of an aggravation unrelated to the study condition,
        can only be included in the study if accepted in writing by the Sponsor's Senior Clinical
        Research Physician.
Male
No healthy subjects accepted to join the trial.
Subject must be at least 10 Years old.


Patient description (medical language): An 8-year-old boy is brought to the clinic by his parents because of weakness and difficulty of standing up from a sitting position. The mother is healthy but had a brother who died in his 20th after being disabled and using wheelchairs in the last few years of his life. Physical examination shows 3/5 lower extremity muscle strength and enlarged calf muscles. The other physical examination and vital signs are unremarkable. Muscle biopsy showed absence of dystrophin protein. The patient is diagnosed with DMD.

Patient description (patient's own words): I brought my  8-year-old son to the doctor's clinic. He was struggling to stand up from a chair for the past few days. My wife is healthy but she was pretty worried since his brother died in his 20s after being disabled and using a wheelchair for the last years of his life. The doctor did an exam which highlighted weakness in the leg muscles and unusually large calf muscles. The rest of the exam was fine, and his vitals were normal. My son did a muscle biopsy, and it showed that the protein important for muscle strength and function is missing. The doctor diagnosed him with Duchenne muscular dystrophy.

Does the patient match the trial criteria? Contradiction