Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (ESSENCE)
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|ClinicalTrials.gov Identifier: NCT02500381|
Recruitment Status : Active, not recruiting
First Posted : July 16, 2015
Last Update Posted : February 21, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Duchenne Muscular Dystrophy||Drug: SRP-4045 Drug: SRP-4053 Drug: Placebo||Phase 3|
This is a double-blind, placebo-controlled, multi-center study to evaluate the efficacy and safety of SRP-4045 and SRP-4053. Eligible participants with out-of-frame deletion mutations amenable to exon 45 or 53 skipping will be randomized to receive once weekly intravenous (IV) infusions of 30 milligrams/kilograms (mg/kg) SRP-4045 or 30 mg/kg SRP-4053 respectively (combined-active group) or placebo for up to 96 weeks (the placebo-controlled period of the trial). This will be followed by an open-label extension period in which all participants will receive open-label active treatment for 48 weeks (up to Week 144 of study).
The study will enroll approximately 222 participants. Twice as many participants will be randomized to receive active treatment as will receive placebo (2:1 randomization).
Clinical efficacy will be assessed at regularly scheduled study visits, including functional tests, such as the 6-minute walk test (6MWT). All participants will undergo a muscle biopsy at baseline and a second muscle biopsy either at Week 48 or Week 96.
Safety will be assessed through the collection of adverse events (AEs), laboratory tests, electrocardiograms (ECGs), echocardiograms (ECHOs), vital signs, and physical examinations throughout the study.
Blood samples will be taken periodically throughout the study to assess the pharmacokinetics of both drugs.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||229 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Part 1 is double-blind and randomized; Part 2 is open-label.|
|Official Title:||A Double-Blind, Placebo-Controlled, Multi-Center Study With an Open-Label Extension to Evaluate the Efficacy and Safety of SRP-4045 and SRP-4053 in Patients With Duchenne Muscular Dystrophy|
|Actual Study Start Date :||September 28, 2016|
|Estimated Primary Completion Date :||October 3, 2025|
|Estimated Study Completion Date :||October 3, 2025|
Participants amenable to exon 45 skipping will receive SRP-4045 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
SRP-4045 solution for IV infusion
Participants amenable to exon 53 skipping will receive SRP-4053 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
SRP-4053 solution for IV infusion
Placebo Comparator: Placebo followed by SRP-4045 or SRP-4053
Participants amenable to exon 45 or 53 skipping will receive SRP-4045 or SRP-4053 placebo-matching IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
SRP-4045 solution for IV infusion
SRP-4053 solution for IV infusion
SRP-4045 or SRP-4053 placebo-matching solution for IV infusion
- Change From Baseline in the Total Distance Walked During 6MWT at Week 96 [ Time Frame: Baseline, Week 96 ]
- Change from Baseline in the Total Distance Walked During 6MWT at Week 144 (Week 48 of the Open-Label Extension Period) [ Time Frame: Baseline, Week 144 ]
- Change from Baseline in Dystrophin Protein Levels Determined by Western Blot at Weeks 48 or 96 [ Time Frame: Baseline, Week 48 or Week 96 ]
- Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Weeks 48 or 96 [ Time Frame: Baseline, Week 48 or Week 96 ]
- Participant's Ability to Rise Independently From the Floor, as indicated by a North Star Ambulatory Assessment (NSAA) Subscore [ Time Frame: Week 96, Week 144 ]The NSAA is a clinician administered scale that rates the participant's performance on various functional activities. During this assessment, the participant's ability to rise independently from the floor (without external support) will be reported as an NSAA subscore of "2" (without modification) or "1" (Gower's maneuver).
- Time to Loss of Ambulation (LOA) [ Time Frame: Baseline, Week 96, and Week 144 ]
- Change From Baseline in the NSAA Total Score at Week 96 and Week 144 [ Time Frame: Baseline, Week 96 and Week 144 ]The NSAA is a clinician administered scale that rates the participant's performance on various functional activities. During this assessment, participants will be asked to perform 17 different functional activities, including a 10 meter walk/run, rising from a sit to standing, standing on 1 leg, climbing a box step, descending a box step, rising from lying to sitting, rising from the floor, lifting the head, standing on heels, and jumping. Participants will be graded as follows: 2 = achieves goal without any assistance; 1 = modified method but achieves goal independent of physical assistance from another person; and 0 = unable to achieve goal independently. NSAA Total Score ranges from 0 to 34, with a score of 34 implying normal function.
- Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 96 and Week 144 [ Time Frame: Baseline, Week 96 and Week 144 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||6 Years to 13 Years (Child)|
|Sexes Eligible for Study:||Male|
|Accepts Healthy Volunteers:||No|
- Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53 skipping
- Stable dose of oral corticosteroids for at least 24 weeks prior to Week 1, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight).
- Intact right and left biceps or 2 alternative upper muscle groups
- Mean 6MWT ≥300 meters and ≤450 meters
- Stable pulmonary function: forced vital capacity (FVC) ≥50% predicted
- Treatment with gene therapy at any time
- Previous treatment with SMT C1100 within 1 week prior to Week 1 and previous treatment with PRO045 (BMN 045), PRO053 (BMN 053), or PRO051 (BMN 051) within 24 weeks prior to Week 1
- Current or previous treatment with any other experimental treatment within 12 weeks prior to Week 1
- Major surgery within 3 months prior to Week 1
- Presence of other clinically significant illness
Other inclusion/exclusion criteria may apply.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02500381
|Study Director:||Medical Director||Sarepta Therapeutics, Inc.|
|Responsible Party:||Sarepta Therapeutics, Inc.|
|Other Study ID Numbers:||
|First Posted:||July 16, 2015 Key Record Dates|
|Last Update Posted:||February 21, 2023|
|Last Verified:||February 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Undecided|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Duchenne muscular dystrophy
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked