Clinical Trials Register

Summary
EudraCT Number:	2016-000602-10
Sponsor's Protocol Code Number:	SNT-III-012
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-09-20
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2016-000602-10

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

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

A.3.2

Name or abbreviated title of the trial where available

SIDEROS

A.4.1

Sponsor's protocol code number

SNT-III-012

A.5.4

Other Identifiers

Name:

US IND

Number:

103801

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Santhera Pharmaceuticals (Switzerland) Limited
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Santhera Pharmaceuticals (Switzerland) Limited
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Santhera Pharmaceuticals (Switzerland) Limited
B.5.2	Functional name of contact point	Quentin Desvigne
B.5.3	Address:
B.5.3.1	Street Address	Hohenrainstrasse 24
B.5.3.2	Town/ city	Pratteln
B.5.3.3	Post code	4133
B.5.3.4	Country	Switzerland
B.5.4	Telephone number	+41619068917
B.5.5	Fax number	+41619068951
B.5.6	E-mail	quentin.desvigne@santhera.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Raxone
D.2.1.1.2	Name of the Marketing Authorisation holder	Santhera Pharmaceuticals (Deutschland) GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/07/437
D.3 Description of the IMP
D.3.1	Product name	Idebenone
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IDEBENONE
D.3.9.1	CAS number	58186-27-9
D.3.9.3	Other descriptive name	IDEBENONE
D.3.9.4	EV Substance Code	SUB08114MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Film-coated tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Duchenne Muscular Dystrophy (DMD)

E.1.1.1

Medical condition in easily understood language

DMD is a genetic disease characterised by rapidly progressive muscle weakness and wasting which leads to severe disability

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10013801
E.1.2	Term	Duchenne muscular dystrophy
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

 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

E.2.2

Secondary objectives of the trial

 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

E.2.3

Trial contains a sub-study

E.3

Principal 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.

E.4

Principal 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 approved 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 Appedix 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 <30 mL/min/1.73 m2).
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).

E.5 End points

E.5.1

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

78 weeks

E.5.2

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

E.5.2.1

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

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Israel

United States

Austria

Belgium

France

Germany

Italy

Netherlands

Spain

Sweden

Switzerland

United Kingdom

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

266

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

200

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

DMD is mainly diagnosed in the first decade of life and therefore patients below the age of consent are expected to be enrolled into the trial

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

130

F.4.2.2

In the whole clinical trial

266

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

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 idebenone is commercially available for patients included in the study or the SIDEROS-E is terminated by the Sponsor whichever occurs first.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-09-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-04-26

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-10-05

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