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

The SIDEROS trial is a randomized, placebo controlled, parallel group study of the efficacy
of idebenone in delaying the loss of respiratory function, whilst also monitoring safety and
tolerability of idebenone in at least 266 DMD patients taking stable dose of concomitant
glucocorticoid steroids.

The study treatment period will be 18 months/ 78 weeks and the idebenone dose will be 900
mg/day. Participants can use deflazacort or prednisolone and be on any dose regimen.

Since glucocorticoid steroids are widely used in ambulant boys from an early age until late
into teenage and even adult years, this study will not take age and ambulatory status into
account and will only exclude patients that need daytime ventilator assistance.

The schedule of assessments will include a Screening Visit and up to 9 protocol visits,
including a Follow-up Visit.

A Screening Visit will take place a maximum of 6 weeks prior to the Baseline Visit (Visit 1,
study day -1). Beginning at Baseline, the patient will receive study medication to be taken
at home, and will undergo regular assessments in the clinic throughout the study period until
Visit 8 at Week 78 at which time the study will be completed and medication discontinued.

All patients completing Visit 8/Week 78, and considered eligible by the Investigator will be
able to participate in an open-label extension study (SIDEROS-E) and will continue to receive
idebenone until the SIDEROS-E is terminated or Marketing Authorization is obtained for
idebenone in DMD, whichever occurs first. The duration of the SIDEROS-E study will be defined
in a separate protocol.

For all patients not participating in the extension study (SIDEROS-E), a Follow-up Visit
(Visit 9/Follow-up Visit) will take place 4 weeks after end of Treatment at Visit 8/Week 78
or after premature discontinuation of study medication.

Each hospital visit will include efficacy assessments (respiratory function assessed by
hospital-based spirometry, oxygen saturation, end-tidal CO2) and safety assessments (adverse
events, concomitant medication, physical examination, vital signs, safety laboratory
evaluations). In addition, respiratory function will be assessed weekly at home with a
hand-held device in order to closely monitor respiratory function between hospital visits.

The study medication, all medical procedures and laboratory testing, and the visits to the
study centre are free of charge. In addition the patients will receive a travel allowance to
cover reasonable expenses to and from the study centre. Participants will not otherwise be
compensated for this study.

Inclusion Criteria:

1. Male patients with a 30% ≤ FVC ≤ 80% of predicted value at Screening and at Baseline.

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 and reproducible repeat FVC within 15% (relative change)
of the screening assessment at Baseline

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 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)

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 (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.