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

NCT02814019 | Terminated Phase 3

• 1 other identifier: SNT-III-012
• Study Type: interventional
• Target: 255
• Locations: 15 countries
• Sites: 63

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

Conditions

Duchenne Muscular Dystrophy (DMD)

Keywords

respiratory function in DMD

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Forced Vital Capacity percent predicted (FVC %p) at Week 78

  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.

  78 weeks

Secondary Outcomes (3)

• Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF %p) at Week 78

  78 weeks

• Change From Baseline in Forced Vital Capacity (FVC) at Week 78

  78 weeks

• Change from Baseline in Inspiratory Flow Reserve (IFR) at Week 78

  78 weeks

Study Arms (2)

idebenone 150 mg film-coated tablets

EXPERIMENTAL

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

Drug: Idebenone 150 mg film-coated tablets

placebo

PLACEBO COMPARATOR

matching placebo tablets

Drug: placebo

Interventions

Idebenone 150 mg film-coated tablets DRUG

idebenone 150 mg film-coated tablets

placebo DRUG

placebo

Eligibility Criteria

• Age: 10 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Minimum 10 years old at Screening.
• Signed and dated Informed Consent Form.
• 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.
• 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).
• Ability to provide reliable FVC values at Screening and Baseline, and reproducible within 15% (relative change) at Baseline compared to Screening.
• 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.
• 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.

You may not qualify if:

• 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.
• 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.
• 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.
• Asthma, bronchitis/COPD, bronchiectasis, emphysema, pneumonia or presence of any other non-DMD respiratory illness that affects respiratory function.
• 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.
• Any bronchopulmonary illness that required treatment with antibiotics within 3 months prior to Screening.
• 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).
• 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.
• Relevant history of or current drug or alcohol abuse, or use of any tobacco or marijuana products/smoking.
• Known individual hypersensitivity to idebenone or to any of the ingredients or excipients of the study medication.
• 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.

Sponsors & Collaborators

• Santhera Pharmaceuticals: lead

Study Sites (63)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Banner University of Arizona Medical Center

Tucson, Arizona, 85724, United States

Location

Childrens Hospital of Los Angeles

Los Angeles, California, 90027, United States

Location

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095, United States

Location

UC Davis Department of Physical Medicine and Rehabilitation

Sacramento, California, 95817, United States

Location

Loma Linda University Healthcare

San Bernardino, California, 92354, United States

Location

Shriners Hospitals for Children-Tampa

Tampa, Florida, 33612, United States

Location

Rare Disease Research

Atlanta, Georgia, 30318, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

University of Kansas

Fairway, Kansas, 66103, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21287, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Gillette Children's Specialty Healthcare

Saint Paul, Minnesota, 55101, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Neurosciences Institute, Neurology - Charlotte Carolinas Healthcare System

Charlotte, North Carolina, 28207, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229-3039, United States

Location

MetroHealth Medical Center

Cleveland, Ohio, 44109-1988, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-1771, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76087, United States

Location

Gottfried von Preyer'sches Kinderspital

Vienna, 1100, Austria

Location

University Hospital Leuven

Leuven, 3000, Belgium

Location

Centre de Référence Neuromusculaire, CHR Citadelle

Liège, 4000, Belgium

Location

Sofia Medical University

Sofia, 1431, Bulgaria

Location

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

Lille, 59037, France

Location

CHRU de Montpellier - Hôpital Gui de Chauliac

Montpellier, 34295, France

Location

Hôpital Hôtel Dieu

Nantes, 44093, France

Location

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

Paris, France

Location

Hôpital des enfants

Toulouse, 31059, France

Location

Universitätsmedizin Berlin Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Uniklinik Köln

Cologne, 50937, Germany

Location

Universitätsklinikum Essen

Essen, 45147, Germany

Location

Universitätsklinik Freiburg Zentrum für Kinderheilkunde und Jugendmedizin

Freiburg im Breisgau, Germany

Location

Universitätsklinikum Hamburg-Eppendorf, Klinik für Kinder- und Jugendmedizin

Hamburg, 20246, Germany

Location

Universitätsklinikum Heidelberg Zentrum für Kinder- und Jugendmedizin

Heidelberg, Germany

Location

Zentrum für neuromuskuläre Erkrankungen

München, Germany

Location

Semmelweis University 2nd Department of Paediatrics

Budapest, Hungary

Location

Children's University Hospital

Dublin, 1, Ireland

Location

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

Petah Tikva, 4920235, Israel

Location

Fondazione IRCCS Eugenio Medea

Bosisio Parini, 23842, Italy

Location

Istituto Giannina Gaslini

Genova, 16147, Italy

Location

Scientific Coordinator Nemo Sud Clinical Center

Messina, 98125, Italy

Location

Centro Clinico NEMO (NEuroMuscular Omnicentre), Niguarda Hospital

Milan, Italy

Location

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

Napoli, 80131, Italy

Location

Reparto Di Neurologia dell'Osperdale Di Padova

Padua, 35122, Italy

Location

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

Pavia, 27100, Italy

Location

U.O.C. Neuropsichiatria Infantile

Roma, 00168, Italy

Location

LUMC

Leiden, Netherlands

Location

Radboud university medical centre

Nijmegen, 6500, Netherlands

Location

Hospital Sant Joan de Déu Neuropediatra

Barcelona, 08950, Spain

Location

Hospital Universitari Vall D' Hebron

Barcelona, 8950, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Hospital La Fe de Valencia

Valencia, 106 46026, Spain

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

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

Basel, 4301, Switzerland

Location

Leeds Teaching Hospital NHS Trust

Leeds, LS1 3EX, United Kingdom

Location

UCL, National Hospital for Neurology and Neurosurgery

London, WC1 3BG, United Kingdom

Location

Great Ormond Street Hospital for Children

London, WC1N 3JH, United Kingdom

Location

John Walton Muscular Dystrophy Research Centre

Newcastle, United Kingdom

Location

Robert Jones and Agnes Hunt Orthopaedic Hospital

Oswestry, SY10 7AG, United Kingdom

Location

Oxford University hospitals NHS Foundation Trust

Oxford, OX39DU, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 25907158 BACKGROUND

• 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.

  PMID: 27238057 BACKGROUND

• 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.

  PMID: 27571420 BACKGROUND

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

idebenone

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2016
• First Posted: June 27, 2016
• Study Start: September 1, 2016
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: December 3, 2021

Record last verified: 2021-11

Locations

CH (1); DE (7); US (20); GB (7); ES (5); FR (5); IL (1); BU (1); HU (1); SE (1); AU (1); IE (1); IT (8); NL (2); BE (2)