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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02814019
Recruitment Status : Active, not recruiting
First Posted : June 27, 2016
Last Update Posted : June 16, 2020
Sponsor:
Information provided by (Responsible Party):
Santhera Pharmaceuticals

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy (DMD) Drug: Idebenone 150 mg film-coated tablets Drug: placebo Phase 3

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 255 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Study Start Date : September 2016
Estimated Primary Completion Date : August 2021
Estimated Study Completion Date : August 2021


Arm Intervention/treatment
Experimental: idebenone 150 mg film-coated tablets
900 mg idebenone/day (2 tablets to be taken 3 times a day with meals)
Drug: Idebenone 150 mg film-coated tablets
Placebo Comparator: placebo
matching placebo tablets
Drug: placebo



Primary Outcome Measures :
  1. Change From Baseline in Forced Vital Capacity percent predicted (FVC %p) at Week 78 [ Time Frame: 78 weeks ]
    Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by changes in FVC %p from Baseline to Week 78 using hospital based spirometry.


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

    Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by:

    •The change from Baseline to Week 78 in PEF %p assessed by hospital-based spirometry measurements


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

    Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by:

    •The time to first 10% decline in FVC (L) during the 78-week treatment period, assessed by hospital-based spirometry measurements


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

    Delaying the loss of respiratory function in patients with DMD receiving glucocorticoid steroids as measured by:

    •The change from Baseline to Week 78 in IFR assessed by hospital-based spirometry measurements




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02814019


Locations
Hide Hide 63 study locations
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United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35233
United States, Arizona
Phoenix Children's Hospital
Phoenix, Arizona, United States, 85016
Banner University of Arizona Medical Center
Tucson, Arizona, United States, 85724
United States, California
Childrens Hospital of Los Angeles
Los Angeles, California, United States, 90027
David Geffen School of Medicine at UCLA
Los Angeles, California, United States, 90095
UC Davis Department of Physical Medicine and Rehabilitation
Sacramento, California, United States, 95817
Loma Linda University Healthcare
San Bernardino, California, United States, 92354
United States, Florida
Shriners Hospitals for Children-Tampa
Tampa, Florida, United States, 33612
United States, Georgia
Rare Disease Research
Atlanta, Georgia, United States, 30318
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas
Fairway, Kansas, United States, 66103
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, Minnesota
Gillette Children's Specialty Healthcare
Saint Paul, Minnesota, United States, 55101
United States, New York
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Neurosciences Institute, Neurology - Charlotte Carolinas Healthcare System
Charlotte, North Carolina, United States, 28207
United States, Ohio
Cincinnati Children's Hospital
Cincinnati, Ohio, United States, 45229-3039
MetroHealth Medical Center
Cleveland, Ohio, United States, 44109-1988
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-1771
United States, Texas
Cook Children's Medical Center
Fort Worth, Texas, United States, 76087
Austria
Gottfried von Preyer'sches Kinderspital
Wien, Austria, 1100
Belgium
University Hospital Leuven
Leuven, Belgium, 3000
Centre de Référence Neuromusculaire, CHR Citadelle
Liège, Belgium, 4000
Bulgaria
Sofia Medical University
Sofia, Bulgaria, 1431
France
Service de neuropédiatrie Pôle Pédiatrie CHRU de Lille - Hôpital Jeanne de Flandre
Lille, France, 59037
CHRU de Montpellier - Hôpital Gui de Chauliac
Montpellier, France, 34295
Hôpital Hôtel Dieu
Nantes, France, 44093
I-Motion - Plateforme d'essais cliniques pédiatriques Hôpital Armand Trousseau bâtiment Lemariey porte 20
Paris, France
Hôpital des enfants
Toulouse, France, 31059
Germany
Universitätsmedizin Berlin Campus Virchow-Klinikum
Berlin, Germany, 13353
Universitätsklinikum Essen
Essen, Germany, 45147
Universitätsklinik Freiburg Zentrum für Kinderheilkunde und Jugendmedizin
Freiburg, Germany
Universitätsklinikum Hamburg-Eppendorf, Klinik für Kinder- und Jugendmedizin
Hamburg, Germany, 20246
Universitätsklinikum Heidelberg Zentrum für Kinder- und Jugendmedizin
Heidelberg, Germany
Uniklinik Köln
Köln, Germany, 50937
Zentrum für neuromuskuläre Erkrankungen
München, Germany
Hungary
Semmelweis University 2nd Department of Paediatrics
Budapest, Hungary
Ireland
Children's University Hospital
Dublin, Ireland, 1
Israel
Institute of Neurology at Schneider Children's Medical Center of Israel
Petah Tiqva, Israel, 4920235
Italy
Fondazione IRCCS Eugenio Medea
Bosisio Parini, Italy, 23842
Istituto Giannina Gaslini
Genova, Italy, 16147
Scientific Coordinator Nemo Sud Clinical Center
Messina, Italy, 98125
Centro Clinico NEMO (NEuroMuscular Omnicentre), Niguarda Hospital
Milano, Italy
Servizio di Cardiomiologia e Genetica Medica, AOU Università degli Studi della Campania "Luigi Vanvitelli"
Napoli, Italy, 80131
Reparto Di Neurologia dell'Osperdale Di Padova
Padova, Italy, 35122
Dipartimento di Clinica Neurologica e Psichiatrica dell'Età Evolutiva della Fondazione IRCCS "C. Mondino" di Pavia
Pavia, Italy, 27100
U.O.C. Neuropsichiatria Infantile
Roma, Italy, 00168
Netherlands
LUMC
Leiden, Netherlands
Radboud university medical centre
Nijmegen, Netherlands, 6500
Spain
Hospital Sant Joan de Déu Neuropediatra
Barcelona, Spain, 08950
Hospital Universitari Vall D' Hebron
Barcelona, Spain, 8950
Hospital Universitario La Paz
Madrid, Spain, 28046
Hospital Universitario Virgen del Rocio
Sevilla, Spain, 41013
Hospital La Fe de Valencia
Valencia, Spain, 106 46026
Sweden
Sahlgrenska University Hospital
Gothenburg, Sweden
Switzerland
Center for neuromuscular disorders, Universitäts-Kinderspital beider Basel (UKBB)
Basel, Switzerland, 4301
United Kingdom
Leeds Teaching Hospital NHS Trust
Leeds, United Kingdom, LS1 3EX
UCL, National Hospital for Neurology and Neurosurgery
London, United Kingdom, WC1 3BG
Great Ormond Street Hospital for Children
London, United Kingdom, WC1N 3JH
John Walton Muscular Dystrophy Research Centre
Newcastle, United Kingdom
Robert Jones and Agnes Hunt Orthopaedic Hospital
Oswestry, United Kingdom, SY10 7AG
Oxford University hospitals NHS Foundation Trust
Oxford, United Kingdom, OX39DU
Royal Hallamshire Hospital
Sheffield, United Kingdom, S10 2JF
Sponsors and Collaborators
Santhera Pharmaceuticals
Additional Information:
Publications:
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Responsible Party: Santhera Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02814019    
Other Study ID Numbers: SNT-III-012
First Posted: June 27, 2016    Key Record Dates
Last Update Posted: June 16, 2020
Last Verified: June 2020
Keywords provided by Santhera Pharmaceuticals:
respiratory function in DMD
Additional relevant MeSH terms:
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Muscular Dystrophy, Duchenne
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Idebenone
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs