|E.1 Medical condition or disease under investigation
|Medical condition(s) being investigated
|Duchenne muscular dystrophy (DMD)
|Medical condition in easily understood language
|This is a genetic condition, which results in muscle degeneration and eventual death.
|Diseases [C] - Musculoskeletal Diseases [C05]
|E.1.2 Medical condition or disease under investigation
|Duchenne muscular dystrophy
|System Organ Class
|10010331 - Congenital, familial and genetic disorders
|Condition being studied is a rare disease
|E.2 Objective of the trial
|Main objective of the trial
|The proposed randomized controlled trial will compare three corticosteroid regimens to address the pragmatic hypothesis that daily corticosteroids (prednisone or deflazacort) will be of greater benefit in terms of function and subject/parent satisfaction than intermittent corticosteroids (prednisone).
|Secondary objectives of the trial
|A second hypothesis is that daily deflazacort will be associated with fewer side effects than daily prednisone. The study protocol includes standardized regimens for the prevention or treatment of predictable side effects of corticosteroid medication, as well as standards of care for the general management of DMD.
|Trial contains a sub-study
|Principal inclusion criteria
|1) Evidence of signed and dated informed consent form indicating that the subject and his parents or guardian (according to local legislation) have been informed about all pertinent aspects of the study. The child might be asked to give his assent, possibly in writing, if considered intellectually capable, in line with the legal requirements in the participating countries and with the permission of the parent(s)/guardian(s). 2) Confirmed diagnosis of Duchenne muscular dystrophy defined as: Male with proximal weakness AND a confirmed DMD mutation in the dystrophin gene (out of frame deletion OR point mutation OR duplication) OR absent/< 3% dystrophin on muscle biopsy (by immunohistochemistry or Western blot). 3) Age ≥ 4 years and < 8 years. 4) Ability to rise independently from floor, from supine to standing, as assessed at screening visit. 5) Willingness and ability to comply with scheduled visits, drug administration plan and study procedures (including laboratory tests, NSAA, 6MWT, ECG, Echo, wrist X-Ray, DXA, PedsQL and TSQM questionnaires) as assessed by the site investigator at the end of the screening period. 6) Ability to maintain reproducible FVC measurements. Boys must have reproducible measurements of FVC. The boy will be observed to insure complete understanding of the instructions and that he has given maximal effort. If the values continue to increase, the boy may be learning and testing will continue, if necessary, beyond the 3 required trials until the boy reaches a plateau. The evaluator will use his/her expert judgment as to whether or not the boy can produce, and will likely be able to continue to produce, a reliable FVC measurement.
|Principal exclusion criteria
|1) History of major renal or hepatic impairment, immunosuppression or other contraindications to corticosteroid therapy. 2) History of chronic systemic fungal or viral infections. Acute bacterial infection (including TB) would exclude from enrollment until the infection had been appropriately treated and resolved. 3) Diabetes mellitus. 4) Idiopathic hypercalcuria. 5) Lack of chicken pox immunity and refusal to undergo immunization. 6) Evidence of symptomatic cardiomyopathy at screening assessment. Asymptomatic cardiac abnormality on investigation would not be an exclusion. 7) Current or previous treatment (greater than four consecutive weeks of oral therapy) with corticosteroids or other immunosuppressive treatments for DMD or other recurrent indications (e.g., asthma). 8) Inability to take capsules, as assessed by the site investigator by the end of the screening period. 9) Allergy/sensitivity to study drugs or their formulations including lactose and/or sucrose intolerance. 10) Severe behavioral problems, including severe autism. 11) Previous or ongoing medical condition, medical history, physical findings or laboratory abnormalities that could affect safety, make it unlikely that treatment and follow up will be correctly completed or impair the assessment of study results, in the judgment of the site investigator. 12) Weight of less than 13 kilograms. 13) Exposure to any investigational drug currently or within 3 months prior to start of study treatment.
|E.5 End points
|Primary end point(s)
|The primary outcome measure is three-dimensional, comprising: • Muscle function (time taken to rise from the floor, from supine to standing) • Respiratory function (Forced Vital Capacity; FVC) • Parent/participant satisfaction with treatment (global satisfaction rating from the Treatment Satisfaction Questionnaire for Medicine (TSQM).
|Timepoint(s) of evaluation of this end point
|The average changes over all post-baseline assessments during the three-to-five-year follow-up period will be of primary interest.
|Secondary end point(s)
|A second hypothesis is that daily deflazacort will be associated with a better side effect profile than daily prednisone. The study protocol includes standardized regimens for prevention/ treatment of predictable side effects of corticosteroid medication, as well as standards of care for the general management of DMD. The trial directly addresses the current chaos in prescribed treatment schedules; its results will have direct impact on the current and future management of boys with DMD throughout the world by providing the evidence base for rational clinical practice. The results of the trial will allow the generation of clear and specific evidence-based guidelines for patient treatment.
|Timepoint(s) of evaluation of this end point
|E.6 and E.7 Scope of the trial
|Scope of the trial
|Trial type and phase
|Human pharmacology (Phase I)
|First administration to humans
|Other trial type description
|Therapeutic exploratory (Phase II)
|Therapeutic confirmatory (Phase III)
|Therapeutic use (Phase IV)
|E.8 Design of the trial
| Comparator of controlled trial
|Other medicinal product(s)
The trial involves single site in the Member State concerned
| The trial involves multiple sites in the Member State concerned
|Number of sites anticipated in Member State concerned
|The trial involves multiple Member States
|Number of sites anticipated in the EEA
|E.8.6 Trial involving sites outside the EEA
|Trial being conducted both within and outside the EEA
|Trial being conducted completely outside of the EEA
|If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
|Trial has a data monitoring committee
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|30 days after last patient, last visit.
|E.8.9 Initial estimate of the duration of the trial
|In the Member State concerned years
|In the Member State concerned months
|In the Member State concerned days
|In all countries concerned by the trial years
|In all countries concerned by the trial months
|In all countries concerned by the trial days