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

This study is currently recruiting participants.
See Contacts and Locations
Verified June 2017 by Sarepta Therapeutics
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics
ClinicalTrials.gov Identifier:
NCT02500381
First received: July 14, 2015
Last updated: June 21, 2017
Last verified: June 2017
  Purpose
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. Additional objectives include evaluation of safety, pharmacokinetics and biomarkers.

Condition Intervention Phase
Duchenne Muscular Dystrophy DMD Muscular Dystrophy Drug: SRP-4045 Drug: SRP-4053 Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
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

Resource links provided by NLM:


Further study details as provided by Sarepta Therapeutics:

Primary Outcome Measures:
  • Change in 6 Minute Walk Test (6MWT) from Baseline [ Time Frame: Baseline to Week 96 ]

Secondary Outcome Measures:
  • Dystrophin protein expression [ Time Frame: Baseline to Week 48 ]
  • Ability to rise independently from the floor [ Time Frame: Baseline to Week 96 ]
  • Functional status as measured by loss of ambulation (LOA) from Baseline [ Time Frame: Baseline to Week 96 ]
  • North Star Ambulatory Assessment (NSAA) from Baseline [ Time Frame: Baseline to Week 96 ]
  • Forced vital capacity (FVC)% predicted from Baseline [ Time Frame: Baseline to Week 96 ]
  • Frequency of falls from Baseline [ Time Frame: Baseline to Week 96 ]
  • Left ventricular ejection fraction (LVEF) from baseline [ Time Frame: Baseline to Week 96 ]

Estimated Enrollment: 99
Actual Study Start Date: August 2016
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: September 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: SRP-4045
A planned minimum of 33 DMD patients with deletion mutations amenable to exon 45 skipping will be randomized to the active SRP-4045 group.
Drug: SRP-4045

SRP-4045 30 mg/kg will be administered as an IV infusion once a week for up to 96 weeks.

In the Open-Label Period, all patients will receive IV infusions of SRP-4045 at 30 mg/kg/week for up to 96 weeks.

Experimental: SRP-4053
A planned minimum of 33 DMD patients with deletion mutations amenable to exon 53 skipping will be randomized to the active SRP-4053 group.
Drug: SRP-4053

SRP-4053 30 mg/kg will be administered as an IV infusion once a week for up to 96 weeks.

In the Open-Label Period, all patients will receive IV infusions of SRP-4053 at 30 mg/kg/week for up to 96 weeks.

Placebo Comparator: Placebo
Approximately 33 DMD patients with deletion mutations amenable to exon 45 or exon 53 skipping will be randomized to the placebo group.
Drug: Placebo

Placebo will be administered as an IV infusion once a week for up to 96 weeks.

In the Open-Label Period, all patients will receive IV infusions of either SRP-4045 or SRP-4053 at 30 mg/kg/week, according to genotype, for up to 96 weeks.


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, 66 patients) or placebo (33 patients) 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 up to 96 weeks.

The study will enroll approximately 99 patients, with a planned minimum target of 45 patients amenable to exon 45 skipping and 45 patients amenable to exon 53 skipping.

Approximately 66 patients will be randomized to receive active treatment with either SRP-4045 or SRP-4053 (depending on deletion mutation), and 33 patients will be randomized to receive placebo. Twice as many patients will receive active treatment as will receive placebo (2:1 randomization).

When approximately 75 patients have been in the trial for 48 weeks a group of independent experts will review key study results and will make a determination on whether patients will roll into the open-label period of the study and receive active drug or continue in the placebo-controlled period out to Week 96 as planned.

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 at Week 48.

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.

  Eligibility

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

Inclusion Criteria:

  • Male 7-13 years old
  • Genotypically confirmed DMD, with genetic deletion amenable to exon 45 or exon 53 skipping
  • Stable dose of corticosteroids for at least 6 months
  • 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 the following experimental compounds: SMT C1100 (BMN-195) at any time
  • Previous treatment with PRO045 or PRO053 within 6 months 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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02500381

Contacts
Contact: Medical Information medinfo@sarepta.com

  Show 44 Study Locations
Sponsors and Collaborators
Sarepta Therapeutics
Investigators
Study Director: Genevieve Laforet, MD, PhD Sarepta Therapeutics
Study Director: Edward M Kaye, MD Sarepta Therapeutics
  More Information

Responsible Party: Sarepta Therapeutics
ClinicalTrials.gov Identifier: NCT02500381     History of Changes
Other Study ID Numbers: 4045-301
Study First Received: July 14, 2015
Last Updated: June 21, 2017
Individual Participant Data  
Plan to Share IPD: Undecided

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

ClinicalTrials.gov processed this record on June 23, 2017