A clinical study to assess how effective and safe is idebenone treatment in patients with Duchenne Muscular Dystrophy (DMD) who are currently receiving Glucocorticoid steroids

• Register: EUCTR
• Last refreshed on: 26 October 2020
• Main ID: EUCTR2016-000602-10-DE
• Date of registration: 30/05/2016
• Prospective Registration: Yes
• Primary sponsor: Santhera Pharmaceuticals (Switzerland) Limited
• Public title: A clinical study to assess how effective and safe is idebenone treatment in patients with Duchenne Muscular Dystrophy (DMD) who are currently receiving Glucocorticoid steroids
• 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 - SIDEROS
• Date of first enrolment: 17/11/2016
• Target sample size: 266
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-000602-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: yes; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: yes; Other: no; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

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

Contacts

• Name: Quentin Desvigne
• Affiliation: Santhera Pharmaceuticals (Switzerland) Limited

• Name: Quentin Desvigne
• Affiliation: Santhera Pharmaceuticals (Switzerland) Limited

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 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 266
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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).



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

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

Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

Intervention(s)

Trade Name: Raxone
Product Name: Idebenone
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IDEBENONE
CAS Number: 58186-27-9
Other descriptive name: IDEBENONE
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 78 weeks

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.

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

Secondary Outcome(s)

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

Secondary ID(s)

SNT-III-012

103801

Source(s) of Monetary Support

Santhera Pharmaceuticals (Switzerland) Limited

Ethics review

Status: Approved
Approval date: 17/11/2016
Contact: