Study of SRP-4045 and SRP-4053 in DMD Patients (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. Identifier: NCT02500381
Recruitment Status : Recruiting
First Posted : July 16, 2015
Last Update Posted : March 23, 2018
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 up to 96 weeks.

The study will enroll approximately 126 patients, with a planned minimum target of 45 patients amenable to exon 45 skipping and 45 patients amenable to exon 53 skipping.

Approximately 84 patients will be randomized to receive active treatment with either SRP-4045 or SRP-4053 (depending on deletion mutation), and 42 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 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 : 126 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 : August 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : June 2021

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 up to 96 weeks.
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 up to 96 weeks.
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 up to 96 weeks.
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 48 [ Time Frame: Baseline and Week 48 ]
  2. 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 in Dystrophin Protein Levels Determined by Western Blot at Weeks 48 or 96 [ Time Frame: Baseline and Weeks 48 or 96 ]
  2. Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Weeks 48 or 96 [ Time Frame: Baseline and Weeks 48 or 96 ]
  3. Ability to Rise Independently From the Floor [ Time Frame: Week 96 ]
  4. Time to Loss of Ambulation (LOA) [ Time Frame: Baseline up to Week 96 ]
  5. Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 96 [ Time Frame: Baseline and Week 96 ]
    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.

  6. Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 96 [ Time Frame: Baseline and Week 96 ]
  7. Change From Baseline in Frequency of Falls at Week 96 [ Time Frame: Baseline and Week 96 ]
  8. Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 96 [ Time Frame: Baseline and Week 96 ]

Information from the National Library of Medicine

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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

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
  • 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

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 identifier (NCT number): NCT02500381

Contact: Medical Information +1 888 727 3782

  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: Melody Badii    310-825-3264   
Principal Investigator: Perry Shieh, MD, PhD         
UC Davis Medical Center Recruiting
Sacramento, California, United States, 95817
Contact: Erica Goude    916-734-0968   
Principal Investigator: Craig McDonald, MD         
Rady Children's Hospital San Diego/ UCSD Recruiting
San Diego, California, United States, 92123
Contact: Rosabel Agbayani    858-966-8208   
Principal Investigator: Carla Grosmann, MD         
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, Connecticut
Connecticut Children's Medical Center Recruiting
Hartford, Connecticut, United States, 06106
Contact: Hendriana Nielsen    860-837-5881   
Principal Investigator: Gyula Acsadi, MD, PhD         
United States, Florida
University of Florida Recruiting
Gainesville, Florida, United States, 32610
Contact: Norane Shehab    352-294-8705   
Principal Investigator: Barry Byrne, MD, PhD         
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, Georgia
Center for Integrative Rare Disease Research (CIRDR) Recruiting
Atlanta, Georgia, United States, 30318
Contact: Bukkie Stephens    678-883-6897   
Principal Investigator: Han Phan, MD         
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
Boston Children's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Contact: Timothy Harrington    857-218-4677   
Principal Investigator: Basil Darras, MD         
United States, Missouri
St. Louis Children's Hospital Recruiting
Saint 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, 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: Paula Casson    513-803-9003   
Principal Investigator: Chet Villa, 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, Oregon
Shriners Hospital for Children Recruiting
Portland, Oregon, United States, 97239
Contact: Cathleen Buckon, OTR/L, MS    503-221-3471   
Principal Investigator: Erika Finanger, MD, MS         
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Michele Bergman    267-425-2111   
Principal Investigator: Gihan Tennekoon, MD         
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
Children's Medical Center Dallas Recruiting
Dallas, Texas, United States, 75235
Contact: Holly Lawrence    214-456-2463   
Principal Investigator: Susan Iannaccone, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Bria Jensen    801-585-9399   
Principal Investigator: Russell Butterfield, MD, PhD         
United States, Virginia
Children's Hospital of the King's Daughters Recruiting
Norfolk, Virginia, United States, 23507
Contact: Terrie Conklin    757-668-9356   
Principal Investigator: Crystal Proud, MD         
United States, Wisconsin
Children's Hospital of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Marsha Malloy    414-266-6792   
Principal Investigator: Matthew Harmelink, MD         
Universitair Ziekenhuis Gent Recruiting
Ghent, Belgium, 9000
Contact: Elke De Vos    +3293321954   
Principal Investigator: Nicolas Deconinck, MD         
Universitair Ziekenhuis Leuven Recruiting
Leuven, Belgium, 3000
Contact: Anne Vanden Eynden    +3216343991   
Principal Investigator: Nathalie Goemans, MD         
Canada, Alberta
Alberta Childrens Hospital Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Tiffany Haig    (403) 955-3192   
Principal Investigator: Jean Mah, MD         
Canada, Ontario
London Health Sciences Centre Recruiting
London, Ontario, Canada, N6A 5W9
Contact: Gina Bhullar    (519) 685-8500 ext 55058   
Principal Investigator: Craig Campbell, MD         
Fakultni nemocnice v Motole Recruiting
Praha, Czechia, 15008
Contact: Marcela Hlozankova    +420224433367   
Principal Investigator: Jana Haberlová, MD         
Hôpital Des Enfants Recruiting
Toulouse, Haute-Garonne, France, 31059
Contact: Françoise Auriol    +33534558589   
Principal Investigator: Claude Cances, MD         
Reference Centre for Neuromuscular Diseases Recruiting
Nantes, France, 44093
Contact: Christelle Peseux    +33240087880   
Principal Investigator: Yann Péréon, MD         
Hôpital Armand Trousseau Recruiting
Paris, France, 75012
Contact: Dominique Duchêne    +33171738313   
Principal Investigator: Laurent Servais, MD, PhD         
Universitätsklinikum Essen Recruiting
Essen, Germany, 45122
Contact: Corinna Seifert    +4920172385170   
Principal Investigator: Ulrike Schara, MD         
University Hospital Freiburg Recruiting
Freiburg, Germany, 79106
Contact: Sabine Wider    +4976127043440   
Principal Investigator: Janbernd Kirschner, MD         
LMU Klinikum der Universität München Recruiting
Munich, Germany, 80337
Contact: Astrid Blaschek    +4989440055110   
Principal Investigator: Wolfgang Müller-Felber, MD         
Schneider Children's Medical Center of Israel Recruiting
Petah Tikvah, Israel, 49102
Contact: Ori Raz    (972) 525-1860 x44   
Principal Investigator: Yoram Nevo, MD         
Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant' Anna Recruiting
Ferrara, Italy, 44124
Contact: Fernanda Fortunato    +393465374262   
Principal Investigator: Alessanda Ferlini, MD, PhD         
Istituto Giannina Gaslini Recruiting
Genoa, Italy, 16147
Contact: Marina Pedemonte, MD    +3901056362675   
Principal Investigator: Claudio Bruno, MD         
Az Ospedaliera Universitaria Policlinico G Martino Recruiting
Messina, Italy, 98125
Contact: Daniela Quattrocchi    +393493500123   
Principal Investigator: Giuseppe Vita, MD         
Policlinico Universitario A Gemelli Recruiting
Rome, Italy, 00168
Contact: Mariarosaria Vizzino    +390630158581   
Principal Investigator: Eugenio Mercuri, MD         
Hospital de La Santa Creu i Sant Pau Recruiting
Barcelona, Spain, 08041
Contact: Nuria Vidal    +34935537115   
Principal Investigator: Jorge Diaz Manera, MD         
Hospital Sant Joan de Deu Recruiting
Barcelona, Spain, 08950
Contact: Marina Garcia    +34936009733   
Principal Investigator: Andres Nascimento, MD         
Hospital Universitari i Politecnic La Fe de Valencia Recruiting
Valencia, Spain
Contact: Pilar Marti    +34961244000   
Principal Investigator: Juan Jesus Vilchez Padilla, MD         
Drottning Silvias Barn Och Ungdomssjukhus Recruiting
Göteborg, Sweden, SE-41685
Contact: Anna-Lena Tulinius    +46313436069   
Principal Investigator: Mar Tulinius, MD         
Not yet recruiting
Stockholm, Sweden
United Kingdom
Leeds Teaching Hospitals NHS Trust Recruiting
Leeds, United Kingdom, LS1 3EX
Contact: Heather Rostron    +441133922344   
Principal Investigator: Ann-Marie Childs, MD         
Alder Hey Childrens Hospital Recruiting
Liverpool, United Kingdom, L12 2AP
Contact: Timothy Henderson    +441512525164   
Principal Investigator: Stefan Spinty, MD         
Great Ormond Street Hospital (GOSH) Recruiting
London, United Kingdom, WC1N 1EH
Contact: Hinal Patel    020 7905 2639 ext 2639   
Principal Investigator: Francesco Muntoni, MD         
Royal Victoria Infirmary Recruiting
Newcastle upon Tyne, United Kingdom, NE1 4LP
Contact: Valerie Corrall    +4401912084569   
Principal Investigator: Volker Straub, MD         
Sponsors and Collaborators
Sarepta Therapeutics
Study Director: Jon Lu, MD, PhD Sarepta Therapeutics
Study Director: Chris Mix, MD, MS Sarepta Therapeutics

Responsible Party: Sarepta Therapeutics Identifier: NCT02500381     History of Changes
Other Study ID Numbers: 4045-301
First Posted: July 16, 2015    Key Record Dates
Last Update Posted: March 23, 2018
Last Verified: February 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
Exon 53
Exon 45

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