Patients with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping MedDRA version: 17.0 Level: PT Classification code 10013801 Term: Duchenne muscular dystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: SRP-4053
Product Code: SRP-4053
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Not Available
CAS Number: 1422959-91-8
Current Sponsor code: SRP-4053
Oth
Sponsors
Sarepta Therapeutics, Inc.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Male aged 6 to 15, inclusive. 2. For treated patients (all patients in Part 1 + 12 additional treated patients in Part 2), established clinical diagnosis of DMD amenable to exon 53 skipping (e.g. deletions of exons such as 42-52, 45-52, 47-52, 48-52, 49-52, 50-52, 52, or 54-58) as documented by a genetic report from an accredited laboratory confirming deletion endpoints by multiplex ligation-dependent probe amplification (MLPA) or sequencing. 3. For Part 2 untreated control patients, established clinical diagnosis of DMD with confirmed genomic deletion of exon(s) not amenable to exon 53 skipping as documented by an accredited laboratory and genomic methodology. 4. Have intact right and left biceps muscles or an alternative upper arm muscle group. 5. Have stable cardiac and pulmonary function that, in the Investigator’s opinion, is unlikely to decompensate over the duration of the study. 6. Achieve a mean distance of two separate assessments on two consecutive days at screening and again at baseline (prior to investigational drug product administration) =250 meters on the 6MWT with the two means being ±15% of each other. (Personal assistance or use of any assistive devices for ambulation is not permitted during the 6MWT.) 7. Patients must meet one of the following two criteria: • NSAA (North Star Ambulatory Assessment) total score >17; or • Rise (Gowers) time =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Use of any pharmacologic treatment, other than corticosteroids, that might have an effect on muscle strength or function within 12 weeks prior to study entry (e.g., growth hormone, anabolic steroids). 2. Previous treatment with the experimental agents BMN-195 (SMT C1100) or PRO053. 3. Previous or current treatment with any other experimental treatments within 12 weeks prior to study entry or participation in any other clinical trial within 6 months prior to study entry. 4. Have a left ventricular ejection fraction (LVEF) of 450 msec. 5. Have a forced vital capacity [FVC] 10 degrees plantar flexion from plantagrade assuming normal range of dorsiflexion of 20 degrees). 10. Change in contracture treatment such as serial casting, contracture control devices, night splints, stretching exercises (passive, active, self) within 3 months prior to enrollment, or expected need for such intervention during the study. 11. Prior or ongoing medical condition that, in the Investigator’s opinion, could interfere with the patient’s participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PART 1 : To evaluate the safety and tolerability of four escalating doses of SRP-4053 administered once weekly for at least 2 weeks per dose level compared to placebo PART 2 : - To assess the effect of SRP-4053 administered weekly on ambulation, endurance, and muscle function as measured by change from Baseline to Week 48 on the 6-Minute Walk Test (6MWT) compared to untreated control patients - To assess the biological activity (dystrophin expression) compared to pre-treatment.;Secondary Objective: PART 1 : To determine the pharmacokinetics of four escalating doses of SRP-4053 administered once weekly for at least 2 weeks per dose level compared to placebo PART 2 : - To assess the safety, tolerability, and pharmacokinetics of SRP-4053 administered weekly compared to untreated control patients - To assess the effect of SRP-4053 on respiratory muscle strength as measured by change from Baseline to Week 48 in maximal inspiratory and expiratory pressure % predicted as compared to untreated control patients;Primary end point(s): PART 1: • Incidence of adverse events (AEs) • Incidence of clinical laboratory abnormalities (hematology, chemistry, coagulation, urinalysis) • Incidence of abnormalities in vital signs and physical examinations • Incidence of abnormalities on electrocardiograms (ECGs) and echocardiograms (ECHO) PART 2: - Functional efficacy endpoint: change from Baseline to Week 48 in the 6-Minute Walk Test (6MWT) - Biological endpoint: change from Baseline at Week 48 in the percentage of dystrophin-positive fibers as determined by immunohistochemistry (IHC);Timepoint(s) of evaluation of this end point: PART 1: • Continuous evaluation of the AEs. • laboratory abnormalities: Screening (-6 to -4), Baseline (-2 to -1), weekly from week 1 to 9, week 12 • vital signs : every week from screening to week 12 • physical examinations : Screening (D1814), week 1, week 4, week 8, week 12 • ECG: Screening , Baseline, week 7 and 12 • ECHO: Screen | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PART 1 and PART 2: - Pharmacokinetic: • Maximum plasma concentration (Cmax) • Time to maximum plasma concentration (tmax) • Area under the plasma concentration-curve (AUC) • Apparent volume of distribution at steady state (Vss) • Elimination half-life (t½) • Total clearance (CL) • Mean residence time (MRT) • Urinary clearance (CLR) PART2: - Functional efficacy endpoint: change from Baseline to Week 48 for the following: • Pulmonary function tests (PFT): maximum expiratory pressure % predicted (MEP % predicted) and maximum inspiratory pressure % predicted (MIP % predicted) - Biological endpoint: change from Baseline at Week 48 for the following: • Dystrophin intensity levels determined by IHC • Dystrophin protein levels determined by Western blot (WB) • Exon 53 skipping determined by reverse transcription-polymerase chain reaction (RT-PCR) - Safety: • Incidence of adverse events • Incidence of clinical laboratory abnormalities (hematology, chemistry, coagulation, urinalysis) • Incidence of abnormalities in vital signs and physical examinations • Incidence of abnormalities on electrocardiograms (ECGs) and echocardiograms (ECHO);Timepoint(s) of evaluation of this end point: PART 1 & 2: - Pharmacokinetic: Part 1 : Week 1, 3, 5, 7 & 12; Part 2: Week 13, 36 & 60 PART 2 : - Efficacy: Screening (-6 to -4) (only new patients), Baseline (-2 to -1), Week 12 (Only control arm), 24, 36,48,60 - Biological: Baseline, Week 60 - Safety: • Continuous evaluation of the AEs • laboratory abnormalities: Screening (new patients only), Baseline, weekly from week 13 to 16, week 20, 24, 28, 32, 36, 48 (excluded control arm), 60 & follow-up • vital signs: every week from screening (new patients only) and baseline to follow-up • physical examinations: Screening (new patients only), week 13, 16, 20, 24, 28, 32,36,48,60 & follow-up • ECG: Screening, Baseline, week 24, 36, 48 & 60 • ECHO: Screening, week 36 & 60 | — |
Countries
France, Italy, United Kingdom
Contacts
Public ContactClinical Trial Operations
Voisin Consulting
Outcome results
None listed