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

• ClinicalTrials.gov Identifier: NCT02500381
• Recruitment Status: Recruiting
• First Posted: July 16, 2015
• Last Update Posted: June 1, 2020
• Sponsor: Sarepta Therapeutics, Inc.
• Information provided by (Responsible Party): Sarepta Therapeutics, Inc.

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 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 Design

• 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

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 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

Outcome Measures

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 ]

Eligibility Criteria

• 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 function: forced vital capacity (FVC) equal to or greater than 50% predicted

Exclusion Criteria:

• Treatment with gene therapy at any time
• Previous treatment with SMT C1100, PRO045 (BMN 045), PRO053 (BMN 053) or PRO051 (BMN 051) 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
• Major surgery within 3 months prior to Week 1
• Presence of other clinically significant illness

Other inclusion/exclusion criteria may apply

Contacts and Locations

Contacts

Contact: Medical Information; +1 800-690-2003; clinicaltrials@sarepta.com

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; Withdrawn

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; Withdrawn

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

Australia, Queensland

Queensland Children's Hospital; Recruiting

Brisbane, Queensland, Australia, 4101

Principal Investigator: Anita Cairns, MD

Australia, Victoria

Royal Children's Hospital Melbourne; Recruiting

Parkville, Victoria, Australia, 3052

Contact: Jemima Mitchell +61399366157 jemima.mitchell@rch.org.au

Principal Investigator: Monique Ryan

The Royal Children Hospital; Recruiting

Parkville, Victoria, Australia, 3052

Principal Investigator: Monique Ryan

Australia

Children's Hospital at Westmead; Recruiting

Westmead, Australia, 2145

Contact: Kaitlyn Griffin +61298450495 kaitlyn.griffin@health.nsw.gov.au

Principal Investigator: Kristi Jones, MD

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

CHR de la Citadelle; Recruiting

Liège, Belgium, 4000

Contact: Laura Buscemi +3243218322 laura.buscemi@chuliege.be

Principal Investigator: Laurent Servais, MD

Bulgaria

University Multiprofile Hospital for Active Treatment Aleksandrovska EAD; Recruiting

Sofia, Sofia-Grad, Bulgaria, 1431

Contact: Tanya Dimitrova +359889320421 taniadimi@abv.bg

Principal Investigator: Ivaylo Tarnev, MD, PhD

Canada, Alberta

Alberta Childrens Hospital; Recruiting

Calgary, Alberta, Canada, T3B 6A8

Contact: Trevor Rutschmann 403-955-3192 Trevor.Rutschmann@albertahealthservices.com

Principal Investigator: Jean Mah, MD

Canada, British Columbia

Children's and Women's Health Centre of British Columbia; Recruiting

Vancouver, British Columbia, Canada, V6H 3V4

Contact: Conrado De Guzman (604) 875-2345 xext6834 conrado.deguzman@cw.bc.ca

Principal Investigator: Kathryn Selby, 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

University Hospital Brno; Recruiting

Brno, Czechia, 61300

Principal Investigator: Lenka Jurikova

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

Greece

IASO Children's Hospital; Recruiting

Maroussi, Greece, 15123

Principal Investigator: Antigone Papavasiliou

Hungary

Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete; Recruiting

Budapest, Hungary, 1083

Contact: Noemi Toreki +3614591492 tnoemy@gmail.com

Principal Investigator: Maria Judith Molnar, 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

Poland

Samodzielny Publiczny Centralny Szpital Kliniczny; Recruiting

Warsaw, Mazowieckie, Poland, 02-097

Contact: Anna Kostera-Pruszczyk, MD, PhD (+48 22) 599 28 57 neurologia1-sekretariat@wum.edu.pl

Principal Investigator: Anna Kostera-Pruszczyk, MD, PhD

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

Royal Hospital for Childrens (Glasgow); Recruiting

Glasgow, United Kingdom, G51 4TF

Principal Investigator: Iain Horrocks

Leeds Teaching Hospitals NHS Trust; Recruiting

Leeds, United Kingdom, LS1 3EX

Contact: Heather Rostron

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); Active, not recruiting

London, United Kingdom, WC1N 1EH

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, Inc.

Investigators

• Study Director: Medical Director; Sarepta Therapeutics, Inc.

More Information

• Responsible Party: Sarepta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02500381
• Other Study ID Numbers: 4045-301
• First Posted: July 16, 2015
• Last Update Posted: June 1, 2020
• Last Verified: May 2020

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, Inc.:

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