Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Sarepta Therapeutics
Information provided by (Responsible Party):
Sarepta Therapeutics Identifier:
First received: July 14, 2015
Last updated: March 28, 2017
Last verified: March 2017
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
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.


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

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 identifier: NCT02500381

Contact: Kara Boniface

  Hide Study Locations
United States, Arizona
Neuromuscular Research Center Recruiting
Phoenix, Arizona, United States, 85028
Contact: Kristy Osgood    480-314-1007   
Principal Investigator: Kumaraswamy Sivakumar, MD         
United States, California
Children's Hospital Los Angeles Recruiting
Los Angeles, California, United States, 90027
Contact: Claudia Dozal    323-361-5825   
Principal Investigator: Leigh Maria Ramos-Platt, MD         
David Geffen School of Medicine, UCLA Recruiting
Los Angeles, California, United States, 90095
Contact: Michael Bonitati    310-825-3264   
Principal Investigator: Perry Shieh, MD, PhD         
Not yet recruiting
Sacramento, California, United States
Stanford University School of Medicine/Medical Center Recruiting
Stanford, California, United States, 94305
Contact: Carolyn Mclaughlin    650-206-3178   
Principal Investigator: John Day, MD         
United States, Florida
Not yet recruiting
Gainesville, Florida, United States
NW Florida Clinical Research Group, LLC Recruiting
Gulf Breeze, Florida, United States, 32561
Contact: Shae Lancelin   
Principal Investigator: Ben Renfroe, MD         
Miami, Florida, United States
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago Recruiting
Chicago, Illinois, United States, 60611
Contact: Theresa Oswald    312-227-4483   
Principal Investigator: Nancy Kuntz, MD         
United States, Iowa
University of Iowa Children's Hospital Recruiting
Iowa City, Iowa, United States, 52242
Contact: Carrie Stephan    319-356-2673   
Principal Investigator: Katherine Mathews, MD         
United States, Kansas
University of Kansas, Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Kiley Sims   
Principal Investigator: Jeffery Statland, MD         
United States, Massachusetts
Not yet recruiting
Boston, Massachusetts, United States
United States, Missouri
St. Louis Children's Hospital Recruiting
St. Louis, Missouri, United States, 63110
Contact: Traci Christenson    314-362-6991   
Principal Investigator: Ann M Connolly, MD         
United States, Nevada
Las Vegas Clinic Recruiting
Las Vegas, Nevada, United States, 89145
Contact: Kaitlyn McKenna    702-505-4230   
Principal Investigator: Jonathan McKinnon, MD         
United States, New York
Not yet recruiting
New York City, New York, United States
University of Rochester Clinical Research Center Recruiting
Rochester, New York, United States, 14642
Contact: Patricia Smith    585-275-4339   
Principal Investigator: Emma Ciafaloni, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center (CCHMC) Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Andrea Collins    513-636-5517   
Principal Investigator: John Jefferies, MD         
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Lisa Moffitt    614-722-8528   
Principal Investigator: Jerry R Mendell, MD         
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC Recruiting
Pittsburgh, Pennsylvania, United States, 15224
Contact: Jennifer M Monahan    412-692-5176   
Principal Investigator: Hoda Z Abdel-Hamid, MD         
United States, Texas
Not yet recruiting
Dallas, Texas, United States
United States, Utah
Not yet recruiting
Salt Lake City, Utah, United States
Not yet recruiting
Ghent, Belgium
Not yet recruiting
Leuven, Belgium
Not yet recruiting
TBD, Canada
Not yet recruiting
Nantes, France
Not yet recruiting
Paris, France
Not yet recruiting
Toulouse, France
Not yet recruiting
Essen, Germany
Not yet recruiting
Freiburg, Germany
Not yet recruiting
Munich, Germany
Not yet recruiting
Ferrara, Italy
Not yet recruiting
Genoa, Italy
Not yet recruiting
Messina, Italy
Not yet recruiting
Rome, Italy
Not yet recruiting
TBD, Netherlands
Not yet recruiting
Barcelona, Spain
Not yet recruiting
Goteborg, Sweden
Not yet recruiting
Stockholm, Sweden
United Kingdom
Not yet recruiting
Leeds, United Kingdom
Not yet recruiting
Liverpool, United Kingdom
Great Ormond Street Hospital (GOSH) Recruiting
London, United Kingdom, WC1N 1EH
Contact: Hinal Patel    020 7905 2639 ext 2639   
Principal Investigator: Francesco Muntoni, MD         
Not yet recruiting
Newcastle upon Tyne, United Kingdom
Sponsors and Collaborators
Sarepta Therapeutics
Study Director: Genevieve Laforet, MD, PhD Sarepta Therapeutics
Study Director: Edward M Kaye, MD Sarepta Therapeutics
  More Information

Responsible Party: Sarepta Therapeutics Identifier: NCT02500381     History of Changes
Other Study ID Numbers: 4045-301
Study First Received: July 14, 2015
Last Updated: March 28, 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 processed this record on April 24, 2017