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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 : November 21, 2018
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics

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.

Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy Drug: SRP-4045 Drug: SRP-4053 Drug: Placebo Phase 3

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 : Interventional  (Clinical Trial)
Estimated Enrollment : 222 participants
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
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 : May 2022
Estimated Study Completion Date : May 2023


Arm Intervention/treatment
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).
Drug: SRP-4045
SRP-4045 solution for IV infusion

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).
Drug: SRP-4053
SRP-4053 solution for IV infusion

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).
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




Primary Outcome Measures :
  1. Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 96 [ Time Frame: Baseline and Week 96 ]

Secondary Outcome Measures :
  1. 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 ]
  2. Change from Baseline in Dystrophin Protein Levels Determined by Western Blot at Weeks 48 or 96 [ Time Frame: Baseline and Weeks 48 or 96 ]
  3. Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Weeks 48 or 96 [ Time Frame: Baseline and Weeks 48 or 96 ]
  4. Ability to Rise Independently From the Floor [ Time Frame: Week 96, Week 144 ]
  5. Time to Loss of Ambulation (LOA) [ Time Frame: Baseline, Week 96, Week 144 ]
  6. 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.

  7. Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 96 and Week 144 [ Time Frame: Baseline, Week 96, Week 144 ]


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Ages Eligible for Study:   7 Years to 13 Years   (Child)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

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 and cardiac function: forced vital capacity (FVC) equal to or greater than 50% predicted and left ventricular ejection fraction (LVEF) greater than 50%

Exclusion Criteria:

  • Previous treatment with SMT C1100 (BMN-195) at any time
  • Treatment with gene therapy at any time
  • Previous treatment with PRO045 or PRO053 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
  • Participation in any other DMD interventional clinical study within 12 weeks prior to Week 1
  • Major surgery within 3 months prior to Week 1
  • Presence of other clinically significant illness
  • Major change in physical therapy regimen within 3 months prior to Week 1

Information from the National Library of Medicine

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


Contacts
Contact: Medical Information +1 888 727 3782 clinicaltrials@sarepta.com

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Sponsors and Collaborators
Sarepta Therapeutics
Investigators
Study Director: Medical Director Sarepta Therapeutics, Inc.

Responsible Party: Sarepta Therapeutics
ClinicalTrials.gov Identifier: NCT02500381     History of Changes
Other Study ID Numbers: 4045-301
First Posted: July 16, 2015    Key Record Dates
Last Update Posted: November 21, 2018
Last Verified: November 2018
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

Keywords provided by Sarepta Therapeutics:
Duchenne muscular dystrophy
Exon Skipping
DMD
Exon 53
Exon 45
Ambulatory
Pediatric
Duchenne

Additional relevant MeSH terms:
Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked