Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (ESSENCE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02500381
Recruitment Status : Recruiting
First Posted : July 16, 2015
Last Update Posted : June 29, 2022
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE July 14, 2015
First Posted Date  ICMJE July 16, 2015
Last Update Posted Date June 29, 2022
Actual Study Start Date  ICMJE September 28, 2016
Estimated Primary Completion Date April 30, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 12, 2021)
Change From Baseline in the Total Distance Walked During 6MWT at Week 96 [ Time Frame: Baseline, Week 96 ]
Original Primary Outcome Measures  ICMJE
 (submitted: July 14, 2015)
Change in 6 Minute Walk Test (6MWT) from Baseline [ Time Frame: Baseline to Week 48 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 12, 2021)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: July 14, 2015)
  • Percentage of dystrophin-positive fibers [ Time Frame: Baseline to Week 24 and 48 ]
  • Change in maximum inspiratory pressure (MIP) % predicted, maximum expiratory pressure (MEP) % predicted from Baseline [ Time Frame: Baseline to Week 48 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD)
Official Title  ICMJE 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
Brief Summary The main objective of this study is to evaluate the efficacy of SRP-4045 (casimersen) and SRP-4053 (golodirsen) compared to placebo in participants with DMD with out-of-frame deletion mutations amenable to skipping exon 45 and exon 53, respectively.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
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.
Primary Purpose: Treatment
Condition  ICMJE Duchenne Muscular Dystrophy
Intervention  ICMJE
  • Drug: SRP-4045
    SRP-4045 solution for IV infusion
    Other Names:
    • Casimersen
    • AMONDYS 45
  • Drug: SRP-4053
    SRP-4053 solution for IV infusion
    Other Names:
    • Golodirsen
    • VYONDYS 53
  • Drug: Placebo
    SRP-4045 or SRP-4053 placebo-matching solution for IV infusion
Study Arms  ICMJE
  • Experimental: SRP-4045
    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).
    Intervention: Drug: SRP-4045
  • Experimental: SRP-4053
    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).
    Intervention: Drug: SRP-4053
  • 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).
    Interventions:
    • Drug: SRP-4045
    • Drug: SRP-4053
    • Drug: Placebo
Publications * Wagner KR, Kuntz NL, Koenig E, East L, Upadhyay S, Han B, Shieh PB. Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double-blind, placebo-controlled, dose-titration trial. Muscle Nerve. 2021 Sep;64(3):285-292. doi: 10.1002/mus.27347. Epub 2021 Jun 29.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 24, 2018)
222
Original Estimated Enrollment  ICMJE
 (submitted: July 14, 2015)
99
Estimated Study Completion Date  ICMJE April 30, 2024
Estimated Primary Completion Date April 30, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 6 Years to 13 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Sarepta Therapeutics Inc., For Clinical Trial Information, Select Option 4 1-888-SAREPTA (1-888-727-3782) SareptAlly@sarepta.com
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Bulgaria,   Canada,   Czechia,   Denmark,   France,   Germany,   Greece,   Hungary,   Ireland,   Israel,   Italy,   Mexico,   Poland,   Russian Federation,   Serbia,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02500381
Other Study ID Numbers  ICMJE 4045-301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Current Responsible Party Sarepta Therapeutics, Inc.
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Sarepta Therapeutics, Inc.
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Sarepta Therapeutics, Inc.
PRS Account Sarepta Therapeutics, Inc.
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP