Phase 2
N=12
Phase I/II Study of SRP-4053 in DMD Patients
Duchenne Muscular Dystrophy
Bottom Line
View on ClinicalTrials.gov: NCT02310906 ↗Enrolled (actual)
12
Serious AEs
8.0%
Results posted
Oct 2020
Primary outcome: Primary: Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Discontinuation — 4; 5; 5; 3 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Placebo (Drug); SRP-4053 (Drug)
- Age
- Pediatric · 6+ yrs
- Sex
- Male
- Sponsor
- Sarepta Therapeutics, Inc.
- Primary completion
- Mar 2019
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Discontinuation |
4; 5; 5; 3; 6; 0 | — |
| PRIMARY Part 1: Number of Participants With Potentially Clinically Significant (PCS) Laboratory Abnormalities Reported as TEAEs |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs |
1; 3; 1; 1; 4 | — |
| PRIMARY Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Physical Examinations |
0; 0; 2; 0; 3 | — |
| PRIMARY Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Reported as TEAEs |
0; 1; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Echocardiograms (ECHO) |
0; 0; 0; 0; 3 | — |
| PRIMARY Part 2a: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 144 in Total Golodirsen Group |
-99.0 | — |
| PRIMARY Part 2b: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 144 in Untreated Group (Non-exon 53 Amenable Participants) |
-160.8 | — |
| PRIMARY Part 2a: Change From Baseline in Dystrophin Protein Levels Determined by Western Blot at Week 48 in Total Golodirsen Group |
0.924 | — |
| SECONDARY Part 1: Maximum Plasma Concentration (Cmax) of Golodirsen |
7840; 17000; 39700; 53300 | — |
| SECONDARY Part 1: Time to Reach Maximum Plasma Concentration (Tmax) of Golodirsen |
1.11; 1.09; 1.12; 1.12 | — |
| SECONDARY Part 1: Area Under the Concentration-Time Curve From Time Zero Extrapolated to the Infinity (AUCinf) of Golodirsen in Plasma |
11800; 26400; 62300; 90800 | — |
| SECONDARY Part 1: Apparent Volume of Distribution at Steady State (Vss) of Golodirsen |
0.670; 0.767; 0.576; 0.668 | — |
| SECONDARY Part 1: Elimination Half-life (T1/2) of Golodirsen |
2.36; 3.63; 3.27; 3.42 | — |
| SECONDARY Part 1: Total Clearance (CL) of Golodirsen |
0.381; 0.405; 0.338; 0.346 | — |
| SECONDARY Part 1: Mean Residence Time (MRT) of Golodirsen |
1.79; 1.92; 1.77; 1.95 | — |
| SECONDARY Part 1: Renal Clearance (CLR) of Golodirsen |
0.345; 0.370; 0.355; 0.374 | — |
| SECONDARY Part 2a: Percent Change From Baseline in Forced Vital Capacity Predicted (FVC%p) at Week144 in Total Golodirsen Group |
-8.382 | — |
| SECONDARY Part 2b: Percent Change From Baseline in Forced Vital Capacity Predicted (FVC%p) at Week144 in Untreated Group (Non-exon 53 Amenable Participants) |
-6.739 | — |
| SECONDARY Part 2a: Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 in Total Golodirsen Group |
0.023 | — |
| SECONDARY Part 2a: Percent Change From Baseline in Exon 53 Skipping Determined by Reverse Transcription Polymerase Chain Reaction (PCR) at Week 48 in Total Golodirsen Group |
16.363 | — |
| SECONDARY Part 2a: Percent Change From Baseline in Dystrophin Positive Fibers Determined by Immunohistochemistry (IHC) at Week 48 in Total Golodirsen Group |
12.508 | — |
Summary
This is a first-in-human, multiple-dose 2-part study to assess the safety, tolerability, efficacy, and pharmacokinetics of SRP-4053 in Duchenne muscular dystrophy (DMD) patients with deletions amenable to exon 53 skipping.
Eligibility Criteria
Inclusion Criteria
- Diagnosed with DMD, genotypically confirmed.
- Intact right and left biceps muscles or an alternative upper arm muscle group.
- Stable pulmonary and cardiac function.
- Minimum performance on 6MWT, North Star Ambulatory Assessment, and rise (Gowers) test as specified in the study protocol.
- On a stable dose of corticosteroids for at least 6 months.
Exclusion Criteria
- Previous treatment with the experimental agents BMN-195 (SMT C1100) or PRO053.
- Current or previous treatment with any other experimental treatments within 12 weeks prior to study entry.
- Major surgery within the last 3 months.
- Presence of other clinically significant illness.
- Major change in physical therapy regime within the last 3 months.
Other inclusion and exclusion criteria may apply.
Data sourced from ClinicalTrials.gov (NCT02310906). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.