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 : April 25, 2018

See Contacts and Locations

Sponsor:

Information provided by (Responsible Party):

Sarepta Therapeutics

Study Description

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% of 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 Design


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

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Duchenne and Becker muscular dystrophy

MedlinePlus related topics: Muscular Dystrophy

Genetic and Rare Diseases Information Center resources: Muscular Dystrophy Duchenne Muscular Dystrophy Becker Muscular Dystrophy

U.S. FDA Resources

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

Change From Baseline in the Total Distance Walked During 6-Minute Walk Test (6MWT) at Week 48 [ Time Frame: Baseline and Week 48 ]
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 :

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 ]
Time to Loss of Ambulation (LOA) [ Time Frame: Baseline up to Week 96 ]
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.
Change From Baseline in Forced Vital Capacity Percent (FVC%) Predicted at Week 96 [ Time Frame: Baseline and Week 96 ]
Change From Baseline in Frequency of Falls at Week 96 [ Time Frame: Baseline and Week 96 ]
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Week 96 [ Time Frame: Baseline and Week 96 ]

Eligibility Criteria

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

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
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

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	medinfo@sarepta.com

Hide Study Locations

Locations


United States, Arizona
Neuromuscular Research Center	Active, not recruiting
Phoenix, Arizona, United States, 85028
United States, California
Children's Hospital Los Angeles	Active, not recruiting
Los Angeles, California, United States, 90027
David Geffen School of Medicine, UCLA	Active, not recruiting
Los Angeles, California, United States, 90095
UC Davis Medical Center	Active, not recruiting
Sacramento, California, United States, 95817
Rady Children's Hospital San Diego/ UCSD	Active, not recruiting
San Diego, California, United States, 92123
Stanford University School of Medicine/Medical Center	Active, not recruiting
Stanford, California, United States, 94305
United States, Connecticut
Connecticut Children's Medical Center	Active, not recruiting
Hartford, Connecticut, United States, 06106
United States, Florida
University of Florida	Active, not recruiting
Gainesville, Florida, United States, 32610
NW Florida Clinical Research Group, LLC	Active, not recruiting
Gulf Breeze, Florida, United States, 32561
	Withdrawn
Miami, Florida, United States
United States, Georgia
Center for Integrative Rare Disease Research (CIRDR)	Active, not recruiting
Atlanta, Georgia, United States, 30318
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago	Active, not recruiting
Chicago, Illinois, United States, 60611
United States, Iowa
University of Iowa Children's Hospital	Active, not recruiting
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas, Medical Center	Active, not recruiting
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Boston Children's Hospital	Active, not recruiting
Boston, Massachusetts, United States, 02115
United States, Missouri
St. Louis Children's Hospital	Active, not recruiting
Saint Louis, Missouri, United States, 63110
United States, Nevada
Las Vegas Clinic	Active, not recruiting
Las Vegas, Nevada, United States, 89145
United States, New York
	Not yet recruiting
New York, New York, United States
University of Rochester Clinical Research Center	Active, not recruiting
Rochester, New York, United States, 14642
United States, Ohio
Cincinnati Children's Hospital Medical Center (CCHMC)	Active, not recruiting
Cincinnati, Ohio, United States, 45229
Nationwide Children's Hospital	Active, not recruiting
Columbus, Ohio, United States, 43205
United States, Oregon
Shriners Hospital for Children	Active, not recruiting
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Philadelphia	Active, not recruiting
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh of UPMC	Active, not recruiting
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Children's Medical Center Dallas	Active, not recruiting
Dallas, Texas, United States, 75235
United States, Utah
University of Utah	Active, not recruiting
Salt Lake City, Utah, United States, 84132
United States, Virginia
Children's Hospital of the King's Daughters	Active, not recruiting
Norfolk, Virginia, United States, 23507
United States, Wisconsin
Children's Hospital of Wisconsin	Active, not recruiting
Milwaukee, Wisconsin, United States, 53226
Belgium
Universitair Ziekenhuis Gent	Recruiting
Ghent, Belgium, 9000
Contact: Elke De Vos +3293321954 elke.devos@uzgent.be
Principal Investigator: Nicolas Deconinck, MD
Universitair Ziekenhuis Leuven	Recruiting
Leuven, Belgium, 3000
Contact: Anne Vanden Eynden +3216343991 anne.vandeneynden@uzleuven.be
Principal Investigator: Nathalie Goemans, MD
Canada, Alberta
Alberta Childrens Hospital	Recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Tiffany Haig (403) 955-3192 tiffany.haig@albertahealthservices.ca
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 gina.bhullar@lhsc.on.ca
Principal Investigator: Craig Campbell, MD
Czechia
Fakultni nemocnice v Motole	Recruiting
Praha, Czechia, 15008
Contact: Marcela Hlozankova +420224433367 m.hlozankova@centrum.cz
Principal Investigator: Jana Haberlová, MD
France
Hôpital Des Enfants	Recruiting
Toulouse, Haute-Garonne, France, 31059
Contact: Françoise Auriol +33534558589 auriol.f@chu-toulouse.fr
Principal Investigator: Claude Cances, MD
Reference Centre for Neuromuscular Diseases	Recruiting
Nantes, France, 44093
Contact: Christelle Peseux +33240087880 christelle.peseux@chu-nantes.fr
Principal Investigator: Yann Péréon, MD
Hôpital Armand Trousseau	Recruiting
Paris, France, 75012
Contact: Dominique Duchêne +33171738313 d.duchene@institut-myologie.org
Principal Investigator: Laurent Servais, MD, PhD
Germany
Universitätsklinikum Essen	Recruiting
Essen, Germany, 45122
Contact: Corinna Seifert +4920172385170 corinna.seifert@uk-essen.de
Principal Investigator: Ulrike Schara, MD
University Hospital Freiburg	Recruiting
Freiburg, Germany, 79106
Contact: Sabine Wider +4976127043440 sabine.wider@uniklinik-freiburg.de
Principal Investigator: Janbernd Kirschner, MD
LMU Klinikum der Universität München	Recruiting
Munich, Germany, 80337
Contact: Astrid Blaschek +4989440055110 astrid.blaschek@med.uni-muenchen.de
Principal Investigator: Wolfgang Müller-Felber, MD
Israel
Schneider Children's Medical Center of Israel	Recruiting
Petah Tikvah, Israel, 49102
Contact: Ori Raz (972) 525-1860 x44 orira1@clalit.org.il
Principal Investigator: Yoram Nevo, MD
Italy
Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant' Anna	Recruiting
Ferrara, Italy, 44124
Contact: Fernanda Fortunato +393465374262 frtfnn@unife.it
Principal Investigator: Alessanda Ferlini, MD, PhD
Istituto Giannina Gaslini	Recruiting
Genoa, Italy, 16147
Contact: Marina Pedemonte, MD +3901056362675 marinapedemonte@gaslini.org
Principal Investigator: Claudio Bruno, MD
Az Ospedaliera Universitaria Policlinico G Martino	Recruiting
Messina, Italy, 98125
Contact: Daniela Quattrocchi +393493500123 danifour@alice.it
Principal Investigator: Giuseppe Vita, MD
Policlinico Universitario A Gemelli	Recruiting
Rome, Italy, 00168
Contact: Mariarosaria Vizzino +390630158581 npi.clinicaltrials@rm.unicatt.it
Principal Investigator: Eugenio Mercuri, MD
Spain
Hospital de La Santa Creu i Sant Pau	Recruiting
Barcelona, Spain, 08041
Contact: Nuria Vidal +34935537115 nvidalf@santpau.cat
Principal Investigator: Jorge Diaz Manera, MD
Hospital Sant Joan de Deu	Recruiting
Barcelona, Spain, 08950
Contact: Marina Garcia +34936009733 mgarciago@fsjd.org
Principal Investigator: Andres Nascimento, MD
Hospital Universitari i Politecnic La Fe de Valencia	Recruiting
Valencia, Spain
Contact: Pilar Marti +34961244000 mapifres@gmail.com
Principal Investigator: Juan Jesus Vilchez Padilla, MD
Sweden
Drottning Silvias Barn Och Ungdomssjukhus	Recruiting
Göteborg, Sweden, SE-41685
Contact: Anna-Lena Tulinius +46313436069 anna-lena.tulinius@vgregion.se
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 heatherrostron@nhs.net
Principal Investigator: Ann-Marie Childs, MD
Alder Hey Childrens Hospital	Recruiting
Liverpool, United Kingdom, L12 2AP
Contact: Timothy Henderson +441512525164 Timothy.Henderson@alderhey.nhs.uk
Principal Investigator: Stefan Spinty, MD
Great Ormond Street Hospital (GOSH)	Recruiting
London, United Kingdom, WC1N 1EH
Contact: Hinal Patel 020 7905 2639 ext 2639 hinal.patel@ucl.ac.uk
Principal Investigator: Francesco Muntoni, MD
Royal Victoria Infirmary	Recruiting
Newcastle upon Tyne, United Kingdom, NE1 4LP
Contact: Valerie Corrall +4401912084569 valerie.corrall@ncl.ac.uk
Principal Investigator: Volker Straub, MD

Sponsors and Collaborators

Sarepta Therapeutics

Investigators


Study Director:	Jon Lu, MD, PhD	Sarepta Therapeutics
Study Director:	Chris Mix, MD, MS	Sarepta Therapeutics

More Information


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:	April 25, 2018
Last Verified:	April 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

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

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