Duchenne Muscular Dystrophy (DMD)
Conditions
Keywords
Duchenne Muscular Dystrophy, DMD, Duchenne
Brief summary
Idebenone is a synthetic analogue of coenzyme Q10 and is a powerful antioxidant and essential constituent of the process of energy production on the cellular level. It can protect mitochondria from oxidative damage and boost their impaired function. It is thought that this mechanism will slow decline in heart function that is part of the disease process of Duchenne Muscular Dystrophy (DMD). It is possible that patients may benefit in terms of muscle strength and respiratory function. This pilot trial is designed to investigate this.
Interventions
DRUGidebenone
idebenone 450 mg/day (150 mg three times a day)
DRUGplacebo
Sponsors
Santhera Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
8 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
* Patients 8 - 16 years of age at time of enrolment * Male * Presence of cardiac involvement/dysfunction, defined by abnormal peak systolic strain in left ventricle (LV) inferolateral wall * Confirmed diagnosis of DMD (out of frame dystrophin gene deletion OR absent/\<5% dystrophin protein on muscle biopsy; clinical picture consistent of typical DMD) * If on chronic glucocorticosteroids treatment (deflazacort, prednisone) for DMD (or any other disease) (i.e. concomitant medication): dosage must be stable (unchanged) 6 months prior to inclusion * If on chronic medication for DMD associated cardiomyopathy (β-blocker, diuretics): dosage must be stable (unchanged) 3 months prior to inclusion * Ability to provide reproducible repeat quantitative muscle testing (QMT) upper limb score within 15% of first assessment score (at Visit1/Day 1 versus Screening Visit
Exclusion criteria
* Symptomatic cardiomyopathy or heart failure * Asymptomatic but severe cardiac dysfunction on baseline (Screening) evaluation: Fractional shortening (FS) \< 20% and/or Ejection fraction (EF) \< 40% * Use of ACE-inhibitors * Previous history of ventricular arrhythmias (other than isolated ventricular extrasystole); ventricular arrhythmias presented at Screening * Previous (6 months or less) participation in any other therapeutic trial for DMD * Use of coenzymeQ10, idebenone, creatine, glutamine, oxatomide, or any herbal medicines within the last 6 months * History of significant concomitant illness or significant impairment of renal or hepatic function * Known individual hypersensitivity to idebenone
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Relative Change in Peak Systolic Radial Strain of the Left Ventricle (LV) Inferolateral Wall From Baseline (at Screening) to Week 52, Assessed by Color Doppler Myocardial Imaging (CDMI). | baseline and Week 52 | * Assessing the peak systolic radial strain of the left ventricle inferolateral wall is used to characterize the cardiac involvement in the DMD patients. * Color Doppler Myocardial Imaging technique is used to quantify regional myocardial function. The cardiac involvement in DMD is characterized by degeneration, atrophy and fibrosis of the myocardium, leading to dilated cardiomyopathy. The process begins in the posterolateral wall of the left ventricle, with septal involvement appearing at later stages. |
Secondary
| Measure | Time frame |
|---|---|
| Respiratory Function: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Maximal Inspiratory Pressure (MIP) and Peak Flow (PF) | 1 year |
| Skeletal Muscle Strength (Upper Limb, Right and Left): Hand Grip, Elbow Flexors and Elbow Extensors (Upper Limb Score) Timed Walking Test (10 Metres) (Ambulant Patients Only) | 1 year |
| Safety and Tolerability, Assessed by Adverse Events, Blood and Urine Laboratory Measures, ECG. | 1 year |
Countries
Belgium
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Idebenone 450 mg/ Day idebenone 150 mg tablet: One tablet 3 times a day (Tid) with meals | 13 |
| Placebo Placebo tablet: One tablet 3 times a day (Tid) with meals | 8 |
| Total | 21 |
Baseline characteristics
| Characteristic | Placebo | Idebenone 450 mg/ Day | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 8 Participants | 13 Participants | 21 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age Continuous | 10.8 years STANDARD_DEVIATION 1.9 | 13.4 years STANDARD_DEVIATION 2.1 | 12.4 years STANDARD_DEVIATION 2 |
| Region of Enrollment Belgium | 8 participants | 13 participants | 21 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 13 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 13 | 8 / 8 |
| serious Total, serious adverse events | 1 / 13 | 1 / 8 |
Outcome results
Primary
The Relative Change in Peak Systolic Radial Strain of the Left Ventricle (LV) Inferolateral Wall From Baseline (at Screening) to Week 52, Assessed by Color Doppler Myocardial Imaging (CDMI).
* Assessing the peak systolic radial strain of the left ventricle inferolateral wall is used to characterize the cardiac involvement in the DMD patients. * Color Doppler Myocardial Imaging technique is used to quantify regional myocardial function. The cardiac involvement in DMD is characterized by degeneration, atrophy and fibrosis of the myocardium, leading to dilated cardiomyopathy. The process begins in the posterolateral wall of the left ventricle, with septal involvement appearing at later stages.
Time frame: baseline and Week 52
Population: At Week 52, data from only 18 patients were available for the primary endpoint analysis due to missing data from 2 patients and the inability to acquire data from a 3rd patient. The efficacy comparison for the primary endpoint was conducted using the LOCF method in the ITT population. In addition, the analysis was repeated using the OC dataset.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Idebenone 450 mg/ Day | The Relative Change in Peak Systolic Radial Strain of the Left Ventricle (LV) Inferolateral Wall From Baseline (at Screening) to Week 52, Assessed by Color Doppler Myocardial Imaging (CDMI). | 104.4 % change in peak systolic | Standard Deviation 92 |
| Placebo | The Relative Change in Peak Systolic Radial Strain of the Left Ventricle (LV) Inferolateral Wall From Baseline (at Screening) to Week 52, Assessed by Color Doppler Myocardial Imaging (CDMI). | 28.9 % change in peak systolic | Standard Deviation 40.7 |
Secondary
Respiratory Function: Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 Second (FEV1), Maximal Inspiratory Pressure (MIP) and Peak Flow (PF)
Time frame: 1 year
Secondary
Safety and Tolerability, Assessed by Adverse Events, Blood and Urine Laboratory Measures, ECG.
Time frame: 1 year
Secondary
Skeletal Muscle Strength (Upper Limb, Right and Left): Hand Grip, Elbow Flexors and Elbow Extensors (Upper Limb Score) Timed Walking Test (10 Metres) (Ambulant Patients Only)
Time frame: 1 year