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

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. Identifier: NCT01027884
Recruitment Status : Completed
First Posted : December 9, 2009
Results First Posted : October 19, 2015
Last Update Posted : October 19, 2015
Information provided by (Responsible Party):
Santhera Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE December 8, 2009
First Posted Date  ICMJE December 9, 2009
Results First Submitted Date  ICMJE June 15, 2015
Results First Posted Date  ICMJE October 19, 2015
Last Update Posted Date October 19, 2015
Study Start Date  ICMJE July 2009
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 23, 2015)
Change From Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 52 [ Time Frame: Baseline and Week 52 ]
Change from Baseline in Percent Predicted Peak Expiratory Flow (PEF) at Week 52
Original Primary Outcome Measures  ICMJE
 (submitted: December 8, 2009)
Primary Objective: to assess the efficacy of idebenone, compared to placebo, in improving or delaying the loss of respiratory function in patients with DMD. Primary endpoint: percent predicted peak expiratory flow (PEF) [ Time Frame: Efficacy assessments: Baseline, Week 13, 26 , 39, 52 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2015)
  • Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52 [ Time Frame: Baseline and Week 52 ]
    Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52
  • Change From Baseline to Week 52 in Muscle Strength [ Time Frame: Baseline and Week 52 ]
    The change from Baseline to Week 52 in muscle strength as measured by Hand-Held Myometry (HHM) was performed following standardized procedures. As almost all patients were non-ambulatory, only analyses of upper limb muscle strength were performed. Results for elbow flexors and for elbow extensors are reported below.The highest value of 3 consecutive measurements with an interval of at least 10 seconds were recorded. The HHM was measured using MicroFET2, a digital hand held muscle tester. The selected unit of measure was Newtons (N).
  • Change From Baseline to Week 52 in Quality of Life Assessed by PedsQL™ Paediatric Quality of Life Inventory [ Time Frame: Baseline and Week 52 ]
    PedsQL Quality of Life Inventory contains paediatric HRQOL measurements: Physical, Emotional,Social and School Functioning. Item Scaling: 5-point Likert scale from 0 (Never) to 4 (Almost always). 3-point scale: 0 (Not at all), 2 (Sometimes) and 4 (A lot) for the Young Child (ages 5-7). Scores are transformed on a scale from 0 to 100 ( 0=100, 1=75, 2=50, 3=25, 4=0) Total Score: Sum of all the items over the number of items answered on all the Scales. The values reported below are overall scores on Paediatric Quality of Life Inventory in Child/Teen Report. These scores were obtained by averaging scores for all the described subscales. The overall scores range between 0-100 with 0 = worst outcome and 100= best outcome
  • Percentage of Patients Reporting Adverse Events [ Time Frame: 52 Weeks ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 8, 2009)
  • Pulmonary function tests [ Time Frame: 12 months ]
  • Muscle strength and motor function [ Time Frame: 12 months ]
  • Quality of life [ Time Frame: 12 months ]
  • Safety and tolerability [ Time Frame: 12 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Phase III Study of Idebenone in Duchenne Muscular Dystrophy (DMD)
Official Title  ICMJE A Phase III Double-Blind, Randomised, Placebo-Controlled Study of the Efficacy, Safety and Tolerability of Idebenone in 10-18 Year Old Patients With Duchenne Muscular Dystrophy
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.
Detailed Description This study was a Phase III, multicenter, randomized, double-blind, placebo-controlled efficacy and safety study. DMD patients (ambulatory and non-ambulatory) at age 10-18 years were enrolled at sites in Europe and North America. Study subjects were randomized in a 1:1 ratio to receive either idebenone (900 mg/day) or placebo 3 times a day with meals for 52 weeks. The primary endpoint was the difference between Catena®/Raxone® and placebo in the change from Baseline to week 52 in Peak Expiratory Flow (PEF as percent predicted, PEF%p, a measure of respiratory muscle strength) as measured by hospital-based spirometry. PEF was also measured by the patient at home using the hand-held ASMA-1 device (secondary endpoint). Other respiratory endpoints included Forced Expiratory Volume in 1 second (as percent predicted, FEV1%p, an additional measure of respiratory muscle strength) and Forced Vital Capacity (as percent predicted, FVC%p, a measure of restrictive lung disease predictive of morbidity and mortality in DMD).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Muscular Dystrophy, Duchenne
  • Ambulatory Care
Intervention  ICMJE
  • Drug: Placebo
    Placebo (900 mg/day) 2 tabl (150 mg each) x 3 times orally with meals
  • Drug: Idebenone
    Idebenone (900 mg/day) 2 tabl (150 mg each) x 3 times orally with meals
    Other Names:
    • CATENA®
    • RAXONE®
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo 900 mg/day
    Intervention: Drug: Placebo
  • Experimental: Idebenone
    Idebenone 900 mg/day
    Intervention: Drug: Idebenone
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 28, 2014)
Original Estimated Enrollment  ICMJE
 (submitted: December 8, 2009)
Actual Study Completion Date  ICMJE April 2014
Actual Primary Completion Date January 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Patients 10 - 18 years of age at Baseline.
  2. Signed and dated informed consent.
  3. 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.
  4. Ability to provide reliable and reproducible repeat PEF within 15% of the first assessment (i.e. Baseline vs. Screening).
  5. 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.

Exclusion Criteria:

  1. Patients dependent on assisted ventilation at Screening and/or Baseline (defined as non-invasive nocturnal ventilation, daytime non-invasive ventilation or continuous invasive ventilation).
  2. 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.
  3. Patients with a percent predicted PEF > 80% at Baseline.
  4. Patients unable to form a mouth seal to allow precise respiratory flow measurements and mouth pressures.
  5. Symptomatic heart failure (high probability of death within one year of Baseline) and/or symptomatic ventricular arrhythmias.
  6. Participation in the previous Phase II or Phase II Extension study (SNT-II-001 or SNT-II-001-E) for idebenone.
  7. Participation in any other therapeutic trial and/or intake of any investigational drug within 90 days prior to Baseline.
  8. Use of carnitine, creatine, glutamine, oxatomide, or any herbal medicines within 30 days prior to Baseline.
  9. 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.
  10. Any previous use of idebenone.
  11. Any concomitant medication with a depressive or stimulating effect on respiration or the respiratory tract.
  12. Planned or expected spinal fixation surgery during the study period (as judged by the investigator).
  13. Asthma, bronchitis/COPD, bronchiectasis, emphysema, pneumonia or the presence of any other non-DMD respiratory illness that affects PEF.
  14. 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.

  15. Moderate or severe hepatic impairment or severe renal impairment.
  16. Prior or ongoing medical condition or laboratory abnormality that in the Investigator's opinion could adversely affect the safety of the subject.

    Please note: Patients who suffer from a severe, unstable condition including (but not limited to) cancer, auto-immune diseases, haematological 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 Medical Monitor.

  17. Relevant history of or current drug or alcohol abuse or use of any tobacco/marijuana products/smoking
  18. Known individual hypersensitivity to idebenone or to any of the ingredients/excipients of the study medication
  19. Systemic glucocorticoid therapy

    1. Chronic use of systemic glucocorticoid therapy for DMD related conditions within 12 months of Baseline (the "12 month non-use period")
    2. More than 2 rounds of acute systemic glucocorticoid burst therapy (of ≤2 week duration) for non-DMD related conditions within the 12 month non-use period
    3. Use of any round of systemic glucocorticoid burst therapy of longer than 2 weeks duration within the 12 month non-use period
    4. Use of systemic glucocorticoid burst therapy less than 8 weeks prior to baseline
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 10 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Austria,   Belgium,   France,   Germany,   Italy,   Netherlands,   Spain,   Sweden,   Switzerland,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT01027884
Other Study ID Numbers  ICMJE SNT-III-003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Santhera Pharmaceuticals
Study Sponsor  ICMJE Santhera Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: 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
PRS Account Santhera Pharmaceuticals
Verification Date September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP