Phase III Study of Idebenone in Duchenne Muscular Dystrophy (DMD)

NCT01027884 | Completed Phase 3 Results DMC

• 1 other identifier: SNT-III-003
• Study Type: interventional
• Target: 65
• Locations: 10 countries
• Sites: 23

Brief Summary

The aim of this Phase III study was to assess the efficacy of idebenone on pulmonary function, motor function, muscle strength and quality of life in patients with DMD. Furthermore, the safety and tolerability of idebenone was assessed.

Conditions

Muscular Dystrophy, Duchenne; Ambulatory Care

Keywords

Idebenone; Duchenne Muscular Dystrophy (DMD); Respiratory function; Ambulatory and non-ambulatory patients; Subjects not using glucocorticoids

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 52

  Change from Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 52

  Baseline and Week 52

Secondary Outcomes (4)

• Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52

  Baseline and Week 52

• Change From Baseline to Week 52 in Muscle Strength

  Baseline and Week 52

• Change From Baseline to Week 52 in Quality of Life Assessed by PedsQL™ Paediatric Quality of Life Inventory

  Baseline and Week 52

• Percentage of Patients Reporting Adverse Events

  52 Weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo 900 mg/day

Drug: Placebo

Idebenone

EXPERIMENTAL

Idebenone 900 mg/day

Drug: Idebenone

Interventions

Placebo DRUG

Placebo (900 mg/day) 2 tabl (150 mg each) x 3 times orally with meals

Placebo

Idebenone DRUG

Idebenone (900 mg/day) 2 tabl (150 mg each) x 3 times orally with meals

Also known as: CATENA®, RAXONE®

Idebenone

Eligibility Criteria

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

You may qualify if:

• Patients 10 - 18 years of age at Baseline.
• Signed and dated informed consent.
• Documented diagnosis of DMD or 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 immunostain.
• Ability to provide reliable and reproducible repeat PEF within 15% of the first assessment (i.e. Baseline vs. 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.

You may not qualify if:

• Patients dependent on assisted ventilation at Screening and/or Baseline (defined as non-invasive nocturnal ventilation, daytime non-invasive ventilation or continuous invasive ventilation).
• Patients with documented DMD-related hypoventilation for which assisted ventilation is needed according to current standard of care guidelines (e.g. FVC\< 30%) or is required in the opinion of the Investigator.
• Patients with a percent predicted PEF \> 80% at Baseline.
• Patients unable to form a mouth seal to allow precise respiratory flow measurements and mouth pressures.
• Symptomatic heart failure (high probability of death within one year of Baseline) and/or symptomatic ventricular arrhythmias.
• Participation in the previous Phase II or Phase II Extension study (SNT-II-001 or SNT-II-001-E) for idebenone.
• Participation in any other therapeutic trial and/or intake of any investigational drug within 90 days prior to Baseline.
• Use of carnitine, creatine, glutamine, oxatomide, or any herbal medicines within 30 days prior to Baseline.
• Use of coenzyme Q10 or vitamin E (if taken at a dose of 5 times above the daily physiological requirement) within 30 days prior to Baseline.
• Any previous use of idebenone.
• Any concomitant medication with a depressive or stimulating effect on respiration or the respiratory tract.
• Planned or expected spinal fixation surgery during the study period (as judged by the investigator).
• Asthma, bronchitis/COPD, bronchiectasis, emphysema, pneumonia or the presence of any other non-DMD respiratory illness that affects PEF.
• Chronic use of beta-2 agonists or any use of other bronchodilating medication (e.g. inhaled steroids, sympathomimetics, anticholinergics).
• Please note: Chronic use if defined as a daily intake for more than 14 days.

Sponsors & Collaborators

• Santhera Pharmaceuticals: lead

Study Sites (23)

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Carolinas Medical Center, Neurosciences and Spine Institute

Charlotte, North Carolina, 28207, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-1771, United States

Location

Monroe Carell, Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9105, United States

Location

Methodist Neurological Institute

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Dr. Günther Bernert, Prim. Univ. Doz.

Vienna, 1100, Austria

Location

University Hospitals Leuven- Children Hospital

Leuven, B - 3000, Belgium

Location

Hôpital Roger Salengro, CHRU Lille

Lille, 59037, France

Location

Prof. Thomas Voit , MD, PhD

Paris, 75651, France

Location

Universitätsklinikum Essen, Zentrum für Kinderheikunde

Essen, D-45122, Germany

Location

Universitätsklinik Freiburg Zentrum für Kinderheilkunde und Jugendmedizin

Freiburg im Breisgau, 79106, Germany

Location

Fondazione IRCCS "Eugenio Medea"

Bosisio Parini, Lecco, 23842, Italy

Location

Azienda Ospedaliera Niguarda Ca' Granda Centro Clinico Nemo

Milan, 20162,, Italy

Location

Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli

Napoli, 80138, Italy

Location

Ass. Prof. Jan Verschuuren , MD, PhD

Leiden, P.O. Box 9600, 2300 RC, Netherlands

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, 46009, Spain

Location

Prof. Thomas Sejersen, MD, PhD

Stockholm, 17176, Sweden

Location

CHUV Lausanne Neuropediatrie

Lausanne, 1011, Switzerland

Location

Related Publications (2)

• 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 RESULT

• Meier T, Rummey C, Leinonen M, Spagnolo P, Mayer OH, Buyse GM; DELOS Study Group. Characterization of pulmonary function in 10-18 year old patients with Duchenne muscular dystrophy. Neuromuscul Disord. 2017 Apr;27(4):307-314. doi: 10.1016/j.nmd.2016.12.014. Epub 2017 Jan 6.

  PMID: 28189481 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne; Respiratory Aspiration

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; Respiration Disorders; Respiratory Tract Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Dr Gunnar Buyse
• Organization: University Hospital Leuven-Children Hospital

gunnar.buyse@uzleuven.be

+32 016343845

Study Officials

• Prof. Gunnar Buyse, MD, PhD.

  University Hospitals Leuven, B-3000, Belgium

  PRINCIPAL INVESTIGATOR

• Dr. Ulrike Schara, MD, PhD

  Universitätsklinikum Essen, D-45122 Essen, Germany

  PRINCIPAL INVESTIGATOR

• Ass. Prof. Jan Verschuuren, MD, PhD

  Leiden University Medical Center (LUMC), 2300 RC Leiden, the Netherlands

  PRINCIPAL INVESTIGATOR

• Dr. Pierre-Yves Jeannet, Médecin Associé, MER

  Unité de Neuropédiatrie, CHUV - BH11, 1011 Lausanne-CH, Switzerland

  PRINCIPAL INVESTIGATOR

• Prof. Thomas Voit, MD, PhD

  Université Pierre et Marie curie VI - Institut de Myologie - groupe hospitalier Pitié Salpétrière - 47/83 boulevard de l'hôpital, 75651 Paris Cedex 13, France

  PRINCIPAL INVESTIGATOR

• Prof. Thomas Sejersen, MD, PhD

  Astrid Lindgrens Barnsjukhus- Karolinska Universitetssjukhuset, SE-17176 Stockholm, Sweden

  PRINCIPAL INVESTIGATOR

• Dr. Günther Bernert, Prim. Univ. Doz.

  Vorstand der Abteilung für Kinder- und Jugendheilkunde, Gottfried v. Preyer'sches Kinderspital, 1100 Wien, Austria

  PRINCIPAL INVESTIGATOR

• Gihan Tennekoon, MD

  Division of Neurology - The Children's Hospital of Philadelphia - 34th Street and Civic Center Blvd, Philadelphia, PA 19104-1771, USA

  PRINCIPAL INVESTIGATOR

• Jean-Marie Cuisset, MD

  Hôpital Roger Salengro, CHRU, Service de neurologie infantile, Lille, France

  PRINCIPAL INVESTIGATOR

• Susan Iannaccone, MD

  University of Texas Southwestern Medical Center, TX, USA

  PRINCIPAL INVESTIGATOR

• Susan Sparks, MD

  The Charlotte-Mecklenburg Hospital Authority, Charlotte, NC, USA

  PRINCIPAL INVESTIGATOR

• Janbernd Kirschner, MD

  Universitätsklinik Freiburg Zentrum für Kinderheilkunde und Jugendmedizin

  PRINCIPAL INVESTIGATOR

• Maria Grazia Nadia D'Angelo, MD

  Fondazione IRCCS "Eugenio Medea"

  PRINCIPAL INVESTIGATOR

• Ksenija Gorni, MD

  Azienda Ospedaliera Niguarda Ca'Granda Centro Clinico Nemo

  PRINCIPAL INVESTIGATOR

• Bryan W. Burnette, MD

  Monroe Carell Jr. Children's Hospital at Vanderbilt

  PRINCIPAL INVESTIGATOR

• Barry Byrne, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

• Michele Yang, MD

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

• Susan Apkon, MD

  Seattle Children's Hospital

  PRINCIPAL INVESTIGATOR

• Ericka Simpson, MD

  Methodist Neurological Institute, Houston

  PRINCIPAL INVESTIGATOR

• Craig McDonald, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

• Luisa Politano, MD

  Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli

  PRINCIPAL INVESTIGATOR

• Ana Camacho Salas, MD

  Hospital Universitario 12 de Octubre

  PRINCIPAL INVESTIGATOR

• Juan Jesus Vilchez, MD

  Hospital Universitari y Politècnic La Fe de Valencia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: December 8, 2009
• First Posted: December 9, 2009
• Study Start: July 1, 2009
• Primary Completion: January 1, 2014
• Study Completion: April 1, 2014
• Last Updated: October 19, 2015
• Results First Posted: October 19, 2015

Record last verified: 2015-09

Locations

CH (1); ES (2); DE (2); US (9); AU (1); BE (1); SE (1); IT (3); NL (1); FR (2)