Phase I/II Study of SRP-4053 in DMD Patients

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02310906
• Date of registration: 03/12/2014
• Prospective Registration: Yes
• Primary sponsor: Sarepta Therapeutics, Inc.
• Public title: Phase I/II Study of SRP-4053 in DMD Patients
• Scientific title: A 2-Part, Randomized, Double-Blind, Placebo-Controlled, Dose-Titration, Safety, Tolerability, and Pharmacokinetics Study (Part 1) Followed by an Open-Label Efficacy and Safety Evaluation (Part 2) of SRP-4053 in Patients With Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping
• Date of first enrolment: January 13, 2015
• Target sample size: 39
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02310906
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

France, Italy, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Sarepta Therapeutics, Inc.

Key inclusion & exclusion 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.



Age minimum: 6 Years
Age maximum: 15 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Duchenne Muscular Dystrophy

Intervention(s)

Drug: Placebo

Drug: SRP-4053

Primary Outcome(s)

Part 1: Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Discontinuation [Time Frame: Baseline up to Week 12]

Part 2a: Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 144 in Total Golodirsen Group [Time Frame: Baseline and Week 144]

Part 2a: Change From Baseline in Dystrophin Protein Levels Determined by Western Blot at Week 48 in Total Golodirsen Group [Time Frame: Baseline, Week 48]

Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Reported as TEAEs [Time Frame: Baseline up to Week 12]

Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Physical Examinations [Time Frame: Baseline up to Week 12]

Part 1: Number of Participants With Potentially Clinically Significant (PCS) Laboratory Abnormalities Reported as TEAEs [Time Frame: Baseline up to Week 12]

Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Echocardiograms (ECHO) [Time Frame: Baseline up to Week 12]

Part 1: Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs Reported as TEAEs [Time Frame: Baseline up to Week 12]

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) [Time Frame: Baseline and Week 144]

Secondary Outcome(s)

Part 1: Elimination Half-life (T1/2) of Golodirsen [Time Frame: Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)]

Part 1: Total Clearance (CL) of Golodirsen [Time Frame: Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)]

Part 2a: Percent Change From Baseline in Dystrophin Positive Fibers Determined by Immunohistochemistry (IHC) at Week 48 in Total Golodirsen Group [Time Frame: Baseline, Week 48]

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 [Time Frame: Baseline, Week 48]

Part 2a: Change From Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Week 48 in Total Golodirsen Group [Time Frame: Baseline, Week 48]

Part 2a: Percent Change From Baseline in Forced Vital Capacity Predicted (FVC%p) at Week144 in Total Golodirsen Group [Time Frame: Baseline, Week 144]

Part 2b: Percent Change From Baseline in Forced Vital Capacity Predicted (FVC%p) at Week144 in Untreated Group (Non-exon 53 Amenable Participants) [Time Frame: Baseline, Week 144]

Part 1: Area Under the Concentration-Time Curve From Time Zero Extrapolated to the Infinity (AUCinf) of Golodirsen in Plasma [Time Frame: Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)]

Part 1: Maximum Plasma Concentration (Cmax) of Golodirsen [Time Frame: Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)]

Part 1: Time to Reach Maximum Plasma Concentration (Tmax) of Golodirsen [Time Frame: Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)]

Part 1: Mean Residence Time (MRT) of Golodirsen [Time Frame: Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)]

Part 1: Apparent Volume of Distribution at Steady State (Vss) of Golodirsen [Time Frame: Pre-dose, 5 to 10 minutes, 1, 1.5, 2, 4, 6, 8, 12, 16 and 24 hours post-dose at Weeks 1 (for 4 mg/kg arm), 3 (for 10 mg/kg arm), 5 (for 20 mg/kg arm) and 7 (for 30 mg/kg arm)]

Part 1: Renal Clearance (CLR) of Golodirsen [Time Frame: 0 to 1440 min after initiation of dosing on Day 1]

Secondary ID(s)

4053-101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Great Ormond Street Hospital for Children NHS Foundation Trust

University College, London

SYSNAV

Institut de Myologie, France

Catholic University of the Sacred Heart

Consultants for Research in Imaging and Spectroscopy

Royal Holloway University

University of Newcastle Upon-Tyne

Results

• Results available: Yes
• Date Posted: 19/10/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02310906