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Study of SRP-4045 and SRP-4053 in DMD Patients (ESSENCE)

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ClinicalTrials.gov Identifier: NCT02500381
Recruitment Status : Recruiting
First Posted : July 16, 2015
Last Update Posted : July 10, 2019
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 July 10, 2019
Actual Study Start Date  ICMJE September 28, 2016
Estimated Primary Completion Date May 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 96 [ Time Frame: Baseline and 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 Complete list of historical versions of study NCT02500381 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2018)
  • Change from Baseline the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 144 (Week 48 of the OL 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 and Weeks 48 or 96 ]
  • Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Weeks 48 or 96 [ Time Frame: Baseline and Weeks 48 or 96 ]
  • Ability to Rise Independently From the Floor [ Time Frame: Week 96, Week 144 ]
  • Time to Loss of Ambulation (LOA) [ Time Frame: Baseline, Week 96, Week 144 ]
  • Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 96 and Week 144 [ Time Frame: Baseline, Week 96, Week 144 ]
    The NSAA is a functional scale devised from the Hammersmith Scale of Motor Ability specifically for use in ambulant children with Duchenne muscular dystrophy (DMD). It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement). The scale assesses activities required to remain functionally ambulant (example, rise from the floor), activities that can be difficult even early in the disease (e.g. standing on heels) and activities that are known to progressively deteriorate over time (stand from a chair, walk). 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, 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 and SRP-4053 in DMD Patients
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 and SRP-4053 compared to placebo in Duchenne muscular dystrophy (DMD) patients 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 patients 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 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 patients will receive open-label active treatment for 48 weeks (up to Week 144 of study).

The study will enroll approximately 222 patients, with a planned minimum target of 111 patients amenable to exon 45 skipping and 111 patients amenable to exon 53 skipping.

Approximately 148 patients will be randomized to receive active treatment with either SRP-4045 or SRP-4053 (depending on deletion mutation), and 74 patients will be randomized to receive placebo. Twice as many patients will 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 six-minute walk test (6MWT). All patients 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
  • Drug: SRP-4053
    SRP-4053 solution for IV infusion
  • Drug: Placebo
    SRP-4045 or SRP-4053 placebo-matching solution for IV infusion
Study Arms  ICMJE
  • Experimental: SRP-4045
    Patients amenable to exon 45 skipping will receive SRP-4045 intravenous (IV) infusions, weekly, at 30 mg/kg for up to 96 weeks in double-blinded period. This will be followed by an open label extension period in which all patients will receive open-label active treatment of SRP-4045 at 30 mg/kg/week IV infusions for 48 weeks in OL period (up to Week 144 in study).
    Intervention: Drug: SRP-4045
  • Experimental: SRP-4053
    Patients amenable to exon 53 skipping will receive SRP-4053 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in double-blinded period. This will be followed by an open label extension period in which all patients will receive open-label active treatment of SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks in OL period (up to Week 144 in study).
    Intervention: Drug: SRP-4053
  • Placebo Comparator: Placebo followed by SRP-4045 or SRP-4053
    Patients 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 double-blinded period. This will be followed by an open label extension period in which all patients will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV for 48 weeks in OL period (up to Week 144 in study).
    Interventions:
    • Drug: SRP-4045
    • Drug: SRP-4053
    • Drug: Placebo
Publications * Not Provided

*   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 May 2023
Estimated Primary Completion Date May 2022   (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
  • Intact right and left biceps or 2 alternative upper muscle groups
  • Mean 6MWT greater than or equal 300 meters and less than or equal to 450 meters
  • Stable pulmonary function: forced vital capacity (FVC) equal to or greater than 50% predicted

Exclusion Criteria:

  • Treatment with gene therapy at any time
  • Previous treatment with SMT C1100, 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 (other than deflazacort) 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
Gender Based Eligibility: Yes
Ages  ICMJE 7 Years to 13 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Information +1 888 727 3782 clinicaltrials@sarepta.com
Listed Location Countries  ICMJE Australia,   Belgium,   Bulgaria,   Canada,   Czechia,   France,   Germany,   Hungary,   Israel,   Italy,   Poland,   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
Responsible Party Sarepta Therapeutics, Inc.
Study Sponsor  ICMJE Sarepta Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Sarepta Therapeutics, Inc.
PRS Account Sarepta Therapeutics, Inc.
Verification Date July 2019

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