Duchenne Muscular Dystrophy MedDRA version: 17.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Santhera Pharmaceuticals (Switzerland) Limited
Eligibility
Sex/Gender
Male
Inclusion 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 =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 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.Changes in the daily amount or the introduction of carnitine, creatine, glutamine, oxatomide, or any herbal medicines (unless written evidence (e.g from the manufacturer or a physician) that the herbal medicine does not contain steroids is provided) at least within 2 weeks 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 ß-agonists or the use of any other bronchodilating medication (i.e. inhaled steroids, sympatomimetics, anti-cholinergics). 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 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. For “glucocorticoid non-users” only a)Chronic use of systemic glucocorticoid therapy for DMD related conditions within 12 months of Baseline (the “12 month non-use period”) b)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 c)Use of any round of systemic glucocorticoid burst therapy of longer than 2 weeks duration within the 12 month non-use period d)Use of systemic glucocorticoid burst therapy less than 8 weeks prior to baseline 20. For “glucocorticoid users” only a)Prior to Final Analysis of randomised “glucocorticoid non-user” subgroup: All “glucocorticoid users” b)After the Final Analysis of randomised “glucocorticoid non-user” subgroup (If Go decision taken i.e. to open “glucocorticoid user” subgroup): Initiation, cessation or any relevant change (i.e. dose change of >15% above any dose adaptation for body weight increase/decrease) in systemic glucocorticoid therapy within 6 months prior to Baseline *Chronic use is defined as a daily intake for more than 14 days.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To assess the efficacy of idebenone, compared to placebo, in improving respiratory function or delaying the loss of respiratory function in patients with DMD;Secondary Objective: •To assess the efficacy of idebenone, compared to placebo, in improving respiratory function or delaying the loss of respiratory function using measures other than those used for the primary endpoint •To assess the efficacy of idebenone, compared to placebo, in improving skeletal muscle strength/motor function or delaying the loss of skeletal muscle strength/motor function •To assess the efficacy of idebenone, compared to placebo, in improving quality of life or delaying the loss in quality of life •To assess the safety and tolerability of idebenone in patients with DMD ;Primary end point(s): The change from Baseline to Week 52 in percent predicted Peak Expiratory Flow (PEF) ;Timepoint(s) of evaluation of this end point: Week 52 after study start | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): In pulmonary function: -The change in percent predicted PEF assessed by weekly home based measurement by the ASMA-1 device -The change from Baseline to Week 52 in percent predicted Forced Vital Capacity (FVC), Peak Cough Flow (PCF), Maximal Expiratory Pressure (MEP) and Maximal Inspiratory Pressure (MIP) -Number of patients in each treatment that begin assisted ventilation during the study period In motor function: -The change from Baseline to Week 52 in muscle strenght as measured by hand-held myometry (HHM) and in motor function as assessed using the Brooke and Vignos scales In quality of life: -The change from Baseline to Week 52 in quality of life assessed by the PedsQL Quality of Life Inventory and Multidimensional Fatigue Scale -Differences in the Clinical Global Impression of efficacy and tolerability at Week 52 between two study arm -Differences between patient responses to the "satisfaction with treatment" question at Week 52 between two study arms -Number of patients in each study arm that during the study period require: acute hospitalization for treatment of a respiratory or other complication associated with disease progression, the initiation of the use of a brace or spinal jacket, initiation or change in systematic glucocorticoid treatment or need for assisted vantilation Measures of safety and tolerability of idebenone ;Timepoint(s) of evaluation of this end point: Week 52 after study start | — |
Countries
Austria, Belgium, France, Germany, Italy, Netherlands, Spain, Sweden, Switzerland, United States
Contacts
Public ContactDr. Gunnar Buyse
University Hospital Leuven-Children Hospital
Outcome results
None listed