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

NCT ID: NCT01027884

Last Updated: 2015-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 65 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2014-04-30

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).

Conditions

Muscular Dystrophy, Duchenne; Ambulatory Care

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo 900 mg/day

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Idebenone

Idebenone 900 mg/day

Group Type: EXPERIMENTAL

Idebenone

Intervention Type: DRUG

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

Interventions

Placebo

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

Intervention Type: DRUG

Idebenone

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

Intervention Type: DRUG

Other Intervention Names

CATENA®; RAXONE®

Eligibility 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

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Santhera Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Prof. Gunnar Buyse, MD, PhD.

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Leuven, B-3000, Belgium

Dr. Ulrike Schara, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinikum Essen, D-45122 Essen, Germany

Ass. Prof. Jan Verschuuren, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Dr. Pierre-Yves Jeannet, Médecin Associé, MER

Role: PRINCIPAL_INVESTIGATOR

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

Prof. Thomas Voit, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Prof. Thomas Sejersen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

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

Dr. Günther Bernert, Prim. Univ. Doz.

Role: PRINCIPAL_INVESTIGATOR

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

Gihan Tennekoon, MD

Role: PRINCIPAL_INVESTIGATOR

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

Jean-Marie Cuisset, MD

Role: PRINCIPAL_INVESTIGATOR

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

Susan Iannaccone, MD

Role: PRINCIPAL_INVESTIGATOR

University of Texas Southwestern Medical Center, TX, USA

Susan Sparks, MD

Role: PRINCIPAL_INVESTIGATOR

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

Janbernd Kirschner, MD

Role: PRINCIPAL_INVESTIGATOR

Universitätsklinik Freiburg Zentrum für Kinderheilkunde und Jugendmedizin

Maria Grazia Nadia D'Angelo, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS "Eugenio Medea"

Ksenija Gorni, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera Niguarda Ca'Granda Centro Clinico Nemo

Bryan W. Burnette, MD

Role: PRINCIPAL_INVESTIGATOR

Monroe Carell Jr. Children's Hospital at Vanderbilt

Barry Byrne, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Michele Yang, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital Colorado

Susan Apkon, MD

Role: PRINCIPAL_INVESTIGATOR

Seattle Children's Hospital

Ericka Simpson, MD

Role: PRINCIPAL_INVESTIGATOR

Methodist Neurological Institute, Houston

Craig McDonald, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, Davis

Luisa Politano, MD

Role: PRINCIPAL_INVESTIGATOR

Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli

Ana Camacho Salas, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitario 12 de Octubre

Juan Jesus Vilchez, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Universitari y Politècnic La Fe de Valencia

Locations

University of California Davis Medical Center

Sacramento, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

University of Florida

Gainesville, Florida, United States

Carolinas Medical Center, Neurosciences and Spine Institute

Charlotte, North Carolina, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Monroe Carell, Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Methodist Neurological Institute

Houston, Texas, United States

Seattle Children's Hospital

Seattle, Washington, United States

Dr. Günther Bernert, Prim. Univ. Doz.

Vienna, , Austria

University Hospitals Leuven- Children Hospital

Leuven, , Belgium

Hôpital Roger Salengro, CHRU Lille

Lille, , France

Prof. Thomas Voit , MD, PhD

Paris, , France

Universitätsklinikum Essen, Zentrum für Kinderheikunde

Essen, , Germany

Universitätsklinik Freiburg Zentrum für Kinderheilkunde und Jugendmedizin

Freiburg im Breisgau, , Germany

Fondazione IRCCS "Eugenio Medea"

Bosisio Parini, Lecco, , Italy

Azienda Ospedaliera Niguarda Ca' Granda Centro Clinico Nemo

Milan, , Italy

Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli

Napoli, , Italy

Ass. Prof. Jan Verschuuren , MD, PhD

Leiden, P.O. Box 9600, Netherlands

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Prof. Thomas Sejersen, MD, PhD

Stockholm, , Sweden

CHUV Lausanne Neuropediatrie

Lausanne, , Switzerland

Countries

United States; Austria; Belgium; France; Germany; Italy; Netherlands; Spain; Sweden; Switzerland

References

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.

Reference Type: RESULT

PMID: 25907158 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28189481 (View on PubMed)

Related Links

http://www.santhera.com

Related Info

Other Identifiers

SNT-III-003

Identifier Type: -

Identifier Source: org_study_id