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

NCT ID: NCT02814019

Last Updated: 2021-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE3

Total Enrollment

255 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-30

Study Completion Date

2020-12-01

Brief Summary

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The purpose of the study is to assess the efficacy of idebenone in delaying the loss of respiratory function in patients with DMD receiving concomitant glucocorticoid steroids

Detailed Description

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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 4 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 idebenone is commercially available for patients included in the study or SIDEROS-E is terminated by the Sponsor, 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.

Conditions

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Duchenne Muscular Dystrophy (DMD)

Keywords

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respiratory function in DMD

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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idebenone 150 mg film-coated tablets

900 mg idebenone/day (2 tablets to be taken 3 times a day with meals)

Group Type EXPERIMENTAL

Idebenone 150 mg film-coated tablets

Intervention Type DRUG

placebo

matching placebo tablets

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Interventions

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Idebenone 150 mg film-coated tablets

Intervention Type DRUG

placebo

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

10 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Santhera Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama

Birmingham, Alabama, United States

Site Status

Phoenix Children's Hospital

Phoenix, Arizona, United States

Site Status

Banner University of Arizona Medical Center

Tucson, Arizona, United States

Site Status

Childrens Hospital of Los Angeles

Los Angeles, California, United States

Site Status

David Geffen School of Medicine at UCLA

Los Angeles, California, United States

Site Status

UC Davis Department of Physical Medicine and Rehabilitation

Sacramento, California, United States

Site Status

Loma Linda University Healthcare

San Bernardino, California, United States

Site Status

Shriners Hospitals for Children-Tampa

Tampa, Florida, United States

Site Status

Rare Disease Research

Atlanta, Georgia, United States

Site Status

University of Iowa

Iowa City, Iowa, United States

Site Status

University of Kansas

Fairway, Kansas, United States

Site Status

Johns Hopkins University

Baltimore, Maryland, United States

Site Status

Children's Hospital Boston

Boston, Massachusetts, United States

Site Status

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, United States

Site Status

University of Rochester Medical Center

Rochester, New York, United States

Site Status

Neurosciences Institute, Neurology - Charlotte Carolinas Healthcare System

Charlotte, North Carolina, United States

Site Status

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Cook Children's Medical Center

Fort Worth, Texas, United States

Site Status

Gottfried von Preyer'sches Kinderspital

Vienna, , Austria

Site Status

University Hospital Leuven

Leuven, , Belgium

Site Status

Centre de Référence Neuromusculaire, CHR Citadelle

Liège, , Belgium

Site Status

Sofia Medical University

Sofia, , Bulgaria

Site Status

Service de neuropédiatrie Pôle Pédiatrie CHRU de Lille - Hôpital Jeanne de Flandre

Lille, , France

Site Status

CHRU de Montpellier - Hôpital Gui de Chauliac

Montpellier, , France

Site Status

Hôpital Hôtel Dieu

Nantes, , France

Site Status

I-Motion - Plateforme d'essais cliniques pédiatriques Hôpital Armand Trousseau bâtiment Lemariey porte 20

Paris, , France

Site Status

Hôpital des enfants

Toulouse, , France

Site Status

Universitätsmedizin Berlin Campus Virchow-Klinikum

Berlin, , Germany

Site Status

Uniklinik Köln

Cologne, , Germany

Site Status

Universitätsklinikum Essen

Essen, , Germany

Site Status

Universitätsklinik Freiburg Zentrum für Kinderheilkunde und Jugendmedizin

Freiburg im Breisgau, , Germany

Site Status

Universitätsklinikum Hamburg-Eppendorf, Klinik für Kinder- und Jugendmedizin

Hamburg, , Germany

Site Status

Universitätsklinikum Heidelberg Zentrum für Kinder- und Jugendmedizin

Heidelberg, , Germany

Site Status

Zentrum für neuromuskuläre Erkrankungen

München, , Germany

Site Status

Semmelweis University 2nd Department of Paediatrics

Budapest, , Hungary

Site Status

Children's University Hospital

Dublin, , Ireland

Site Status

Institute of Neurology at Schneider Children's Medical Center of Israel

Petah Tikva, , Israel

Site Status

Fondazione IRCCS Eugenio Medea

Bosisio Parini, , Italy

Site Status

Istituto Giannina Gaslini

Genova, , Italy

Site Status

Scientific Coordinator Nemo Sud Clinical Center

Messina, , Italy

Site Status

Centro Clinico NEMO (NEuroMuscular Omnicentre), Niguarda Hospital

Milan, , Italy

Site Status

Servizio di Cardiomiologia e Genetica Medica, AOU Università degli Studi della Campania "Luigi Vanvitelli"

Napoli, , Italy

Site Status

Reparto Di Neurologia dell'Osperdale Di Padova

Padua, , Italy

Site Status

Dipartimento di Clinica Neurologica e Psichiatrica dell'Età Evolutiva della Fondazione IRCCS "C. Mondino" di Pavia

Pavia, , Italy

Site Status

U.O.C. Neuropsichiatria Infantile

Roma, , Italy

Site Status

LUMC

Leiden, , Netherlands

Site Status

Radboud university medical centre

Nijmegen, , Netherlands

Site Status

Hospital Sant Joan de Déu Neuropediatra

Barcelona, , Spain

Site Status

Hospital Universitari Vall D' Hebron

Barcelona, , Spain

Site Status

Hospital Universitario La Paz

Madrid, , Spain

Site Status

Hospital Universitario Virgen del Rocio

Seville, , Spain

Site Status

Hospital La Fe de Valencia

Valencia, , Spain

Site Status

Sahlgrenska University Hospital

Gothenburg, , Sweden

Site Status

Center for neuromuscular disorders, Universitäts-Kinderspital beider Basel (UKBB)

Basel, , Switzerland

Site Status

Leeds Teaching Hospital NHS Trust

Leeds, , United Kingdom

Site Status

UCL, National Hospital for Neurology and Neurosurgery

London, , United Kingdom

Site Status

Great Ormond Street Hospital for Children

London, , United Kingdom

Site Status

John Walton Muscular Dystrophy Research Centre

Newcastle, , United Kingdom

Site Status

Robert Jones and Agnes Hunt Orthopaedic Hospital

Oswestry, , United Kingdom

Site Status

Oxford University hospitals NHS Foundation Trust

Oxford, , United Kingdom

Site Status

Royal Hallamshire Hospital

Sheffield, , United Kingdom

Site Status

Countries

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

References

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Buyse GM, Voit T, Schara U, Straathof CSM, D'Angelo MG, Bernert G, Cuisset JM, Finkel RS, Goemans N, McDonald CM, Rummey C, Meier T; DELOS Study Group. Efficacy of idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids (DELOS): a double-blind randomised placebo-controlled phase 3 trial. Lancet. 2015 May 2;385(9979):1748-1757. doi: 10.1016/S0140-6736(15)60025-3. Epub 2015 Apr 20.

Reference Type BACKGROUND
PMID: 25907158 (View on PubMed)

McDonald CM, Meier T, Voit T, Schara U, Straathof CS, D'Angelo MG, Bernert G, Cuisset JM, Finkel RS, Goemans N, Rummey C, Leinonen M, Spagnolo P, Buyse GM; DELOS Study Group. Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy. Neuromuscul Disord. 2016 Aug;26(8):473-80. doi: 10.1016/j.nmd.2016.05.008. Epub 2016 May 12.

Reference Type BACKGROUND
PMID: 27238057 (View on PubMed)

Buyse GM, Voit T, Schara U, Straathof CS, D'Angelo MG, Bernert G, Cuisset JM, Finkel RS, Goemans N, Rummey C, Leinonen M, Mayer OH, Spagnolo P, Meier T, McDonald CM; DELOS Study Group. Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy. Pediatr Pulmonol. 2017 Apr;52(4):508-515. doi: 10.1002/ppul.23547. Epub 2016 Aug 29.

Reference Type BACKGROUND
PMID: 27571420 (View on PubMed)

Other Identifiers

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SNT-III-012

Identifier Type: -

Identifier Source: org_study_id