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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Santhera Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT01027884
First received: December 8, 2009
Last updated: June 5, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Muscular Dystrophy, Duchenne
Ambulatory Care
Drug: Idebenone (CATENA®/RAXONE®)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Santhera Pharmaceuticals:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Pulmonary function tests [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Muscle strength and motor function [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Safety and tolerability [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 65
Study Start Date: July 2009
Study Completion Date: April 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Idebenone (CATENA®/RAXONE®)
Idebenone (900 mg idebenone/day) 2 tabl (150 mg each) x 3 times orally with meals
Experimental: Idebenone
Idebenone 900 mg/day
Drug: Idebenone (CATENA®/RAXONE®)
Idebenone (900 mg idebenone/day) 2 tabl (150 mg each) x 3 times orally with meals

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).

  Eligibility

Ages Eligible for Study:   10 Years to 18 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01027884

  Show 23 Study Locations
Sponsors and Collaborators
Santhera Pharmaceuticals
Investigators
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
  More Information

Additional Information:
No publications provided

Responsible Party: Santhera Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01027884     History of Changes
Other Study ID Numbers: SNT-III-003
Study First Received: December 8, 2009
Last Updated: June 5, 2014
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Santhera Pharmaceuticals:
Idebenone
Duchenne Muscular Dystrophy (DMD)
Respiratory function
Ambulatory and non-ambulatory patients
Subjects not using glucocorticoids

Additional relevant MeSH terms:
Muscular Dystrophy, Duchenne
Muscular Dystrophies
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Idebenone
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 27, 2014