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

• Register: ClinicalTrials.gov
• Last refreshed on: 6 December 2021
• Main ID: NCT02814019
• Date of registration: 17/06/2016
• Prospective Registration: Yes
• Primary sponsor: Santhera Pharmaceuticals
• Public title: A Phase III Double-blind Study With Idebenone in Patients With Duchenne Muscular Dystrophy (DMD) Taking Glucocorticoid Steroids SIDEROS
• Scientific title: A Phase III Double-blind, Randomized, Placebo-Controlled Study Assessing the Efficacy, Safety and Tolerability of Idebenone in Patients With Duchenne Muscular Dystrophy Receiving Glucocorticoid Steroids
• Date of first enrolment: September 2016
• Target sample size: 255
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT02814019
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Austria, Belgium, Bulgaria, France, Germany, Hungary, Ireland, Israel, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States

Key inclusion & exclusion 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.



Age minimum: 10 Years
Age maximum: N/A
Gender: Male

Health Condition(s) or Problem(s) studied

Duchenne Muscular Dystrophy (DMD)

Intervention(s)

Drug: placebo

Drug: Idebenone 150 mg film-coated tablets

Primary Outcome(s)

Change From Baseline in Forced Vital Capacity percent predicted (FVC %p) at Week 78 [Time Frame: 78 weeks]

Secondary Outcome(s)

Change from Baseline in Inspiratory Flow Reserve (IFR) at Week 78 [Time Frame: 78 weeks]

Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF %p) at Week 78 [Time Frame: 78 weeks]

Change From Baseline in Forced Vital Capacity (FVC) at Week 78 [Time Frame: 78 weeks]

Secondary ID(s)

SNT-III-012

Source(s) of Monetary Support

Please refer to primary and secondary sponsors