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

Primary Purpose

Muscular Dystrophy, Duchenne, Ambulatory Care

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Placebo

Idebenone

About this trial

This is an interventional treatment trial for Muscular Dystrophy, Duchenne focused on measuring Idebenone, Duchenne Muscular Dystrophy (DMD), Respiratory function, Ambulatory and non-ambulatory patients, Subjects not using glucocorticoids

Eligibility Criteria

10 Years - 18 Years (Child, Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.
Moderate or severe hepatic impairment or severe renal impairment.
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.
Relevant history of or current drug or alcohol abuse or use of any tobacco/marijuana products/smoking
Known individual hypersensitivity to idebenone or to any of the ingredients/excipients of the study medication
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

Sites / Locations

University of California Davis Medical Center
Children's Hospital Colorado
University of Florida
Carolinas Medical Center, Neurosciences and Spine Institute
The Children's Hospital of Philadelphia
Monroe Carell, Jr. Children's Hospital at Vanderbilt
University of Texas Southwestern Medical Center
Methodist Neurological Institute
Seattle Children's Hospital
Dr. Günther Bernert, Prim. Univ. Doz.
University Hospitals Leuven- Children Hospital
Hôpital Roger Salengro, CHRU Lille
Prof. Thomas Voit , MD, PhD
Universitätsklinikum Essen, Zentrum für Kinderheikunde
Universitätsklinik Freiburg Zentrum für Kinderheilkunde und Jugendmedizin
Fondazione IRCCS "Eugenio Medea"
Azienda Ospedaliera Niguarda Ca' Granda Centro Clinico Nemo
Azienda Ospedaliera Universitaria della Seconda Università degli Studi di Napoli
Ass. Prof. Jan Verschuuren , MD, PhD
Hospital Universitario 12 de Octubre
Hospital Universitario y Politécnico La Fe
Prof. Thomas Sejersen, MD, PhD
CHUV Lausanne Neuropediatrie

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Idebenone

Arm Description

Placebo 900 mg/day

Idebenone 900 mg/day

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Change From Baseline to Week 52 in Muscle Strength

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

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

Full Information

NCT ID

NCT01027884

First Posted

December 8, 2009

Last Updated

September 23, 2015

Sponsor

Santhera Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT01027884

Brief Title

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

Acronym

DELOS

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2015

Overall Recruitment Status

Completed

Study Start Date

July 2009 (undefined)

Primary Completion Date

January 2014 (Actual)

Study Completion Date

April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Santhera Pharmaceuticals

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Muscular Dystrophy, Duchenne, Ambulatory Care

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

65 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo 900 mg/day

Arm Title

Idebenone

Arm Type

Experimental

Arm Description

Idebenone 900 mg/day

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Idebenone

Other Intervention Name(s)

CATENA®, RAXONE®

Intervention Description

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

Primary Outcome Measure Information:

Title

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

Description

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

Time Frame

Baseline and Week 52

Secondary Outcome Measure Information:

Title

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

Description

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

Time Frame

Baseline and Week 52

Title

Change From Baseline to Week 52 in Muscle Strength

Description

Time Frame

Baseline and Week 52

Title

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

Description

Time Frame

Baseline and Week 52

Title

Percentage of Patients Reporting Adverse Events

Time Frame

52 Weeks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

10 Years

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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. Moderate or severe hepatic impairment or severe renal impairment. 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. Relevant history of or current drug or alcohol abuse or use of any tobacco/marijuana products/smoking Known individual hypersensitivity to idebenone or to any of the ingredients/excipients of the study medication Systemic glucocorticoid therapy Chronic use of systemic glucocorticoid therapy for DMD related conditions within 12 months of Baseline (the "12 month non-use period") 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 Use of any round of systemic glucocorticoid burst therapy of longer than 2 weeks duration within the 12 month non-use period Use of systemic glucocorticoid burst therapy less than 8 weeks prior to baseline

Overall Study Officials: