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Study of SRP-4045 and SRP-4053 in Participants With Duchenne Muscular Dystrophy (DMD) (ESSENCE)

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ClinicalTrials.gov Identifier: NCT02500381
Recruitment Status : Recruiting
First Posted : July 16, 2015
Last Update Posted : August 19, 2021
Sponsor:
Information provided by (Responsible Party):
Sarepta Therapeutics, Inc.

Brief Summary:
The main objective of this study is to evaluate the efficacy of SRP-4045 and SRP-4053 compared to placebo in participants with DMD 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 participants 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 milligrams/kilograms (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 participants will receive open-label active treatment for 48 weeks (up to Week 144 of study).

The study will enroll approximately 222 participants. Twice as many participants will be randomized to 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 6-minute walk test (6MWT). All participants 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.

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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 : April 30, 2024
Estimated Study Completion Date : April 30, 2024


Arm Intervention/treatment
Experimental: SRP-4045
Participants amenable to exon 45 skipping will receive SRP-4045 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
Drug: SRP-4045
SRP-4045 solution for IV infusion
Other Names:
  • Casimersen
  • AMONDYS 45

Experimental: SRP-4053
Participants amenable to exon 53 skipping will receive SRP-4053 IV infusions, weekly, at 30 mg/kg for up to 96 weeks in the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
Drug: SRP-4053
SRP-4053 solution for IV infusion
Other Names:
  • Golodirsen
  • VYONDYS 53

Placebo Comparator: Placebo followed by SRP-4045 or SRP-4053
Participants 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 the double-blinded period. This will be followed by an open-label extension period in which all participants will receive open-label active treatment of SRP-4045 or SRP-4053 at 30 mg/kg/week IV infusions for 48 weeks (up to Week 144 in the study).
Drug: SRP-4045
SRP-4045 solution for IV infusion
Other Names:
  • Casimersen
  • AMONDYS 45

Drug: SRP-4053
SRP-4053 solution for IV infusion
Other Names:
  • Golodirsen
  • VYONDYS 53

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 6MWT at Week 96 [ Time Frame: Baseline, Week 96 ]

Secondary Outcome Measures :
  1. Change from Baseline in the Total Distance Walked During 6MWT at Week 144 (Week 48 of the Open-Label Extension 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, Week 48 or Week 96 ]
  3. Change from Baseline in Dystrophin Intensity Levels Determined by Immunohistochemistry (IHC) at Weeks 48 or 96 [ Time Frame: Baseline, Week 48 or Week 96 ]
  4. Participant's Ability to Rise Independently From the Floor, as indicated by a North Star Ambulatory Assessment (NSAA) Subscore [ Time Frame: Week 96, Week 144 ]
    The NSAA is a clinician administered scale that rates the participant's performance on various functional activities. During this assessment, the participant's ability to rise independently from the floor (without external support) will be reported as an NSAA subscore of "2" (without modification) or "1" (Gower's maneuver).

  5. Time to Loss of Ambulation (LOA) [ Time Frame: Baseline, Week 96, and Week 144 ]
  6. Change From Baseline in the NSAA Total Score at Week 96 and Week 144 [ Time Frame: Baseline, Week 96 and Week 144 ]
    The NSAA is a clinician administered scale that rates the participant's performance on various functional activities. During this assessment, participants will be asked to perform 17 different functional activities, including a 10 meter walk/run, rising from a sit to standing, standing on 1 leg, climbing a box step, descending a box step, rising from lying to sitting, rising from the floor, lifting the head, standing on heels, and jumping. Participants will be graded as follows: 2 = achieves goal without any assistance; 1 = modified method but achieves goal independent of physical assistance from another person; and 0 = unable to achieve goal independently. 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 and Week 144 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 13 Years   (Child)
Sexes Eligible for Study:   Male
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 prior to Week 1, and the dose is expected to remain constant throughout the study (except for modifications to accommodate changes in weight).
  • Intact right and left biceps or 2 alternative upper muscle groups
  • Mean 6MWT ≥300 meters and ≤450 meters
  • Stable pulmonary function: forced vital capacity (FVC) ≥50% predicted

Exclusion Criteria:

  • Treatment with gene therapy at any time
  • Previous treatment with SMT C1100 within 1 week prior to Week 1 and previous treatment with 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 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.


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

Locations
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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
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
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 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, Victoria
Royal Children's Hospital Melbourne Not yet recruiting
Parkville, Victoria, Australia, 3052
Contact: Jemima Mitchell    +61399366157    jemima.mitchell@rch.org.au   
Principal Investigator: Monique Ryan, MD         
Australia
Children's Hospital at Westmead Recruiting
Westmead, Australia, 2145
Contact: Kaitlyn Griffin    +61298450495    kaitlyn.griffin@health.nsw.gov.au   
Principal Investigator: Michelle Lorentzos, 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: Liesbeth De Waele, MD, PHD         
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         
Children's Hospital of Eastern Ontario Recruiting
Ottawa, Ontario, Canada, K1H 8L1
Contact: Rosa Ramos       rramos@cheo.on.ca   
Principal Investigator: Hans Lochmuller, MD         
Czechia
University Hospital Brno Recruiting
Brno, Czechia, 61300
Principal Investigator: Lenka Jurikova, MD         
Fakultni nemocnice v Motole Recruiting
Praha, Czechia, 15008
Contact: Marcela Hlozankova    +420224433367    m.hlozankova@centrum.cz   
Principal Investigator: Jana Haberlová, MD         
Denmark
Rigshospitalet Copenhagen University Hospital Recruiting
København Ø, Denmark, 2100
Principal Investigator: Christina Hoi-Hansen, 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
Charité - Universitätsmedizin Berlin Recruiting
Berlin, Germany, 13353
Contact: Regina Rybka Golm    +49 30 450 66 10 44    regina.rybka-golm@charite.de   
Principal Investigator: Claudia Weiss, MD         
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: David Schorling, MD         
Greece
IASO Children's Hospital Recruiting
Maroussi, Greece, 15123
Contact: Maria Konstantinou    +306931838751      
Principal Investigator: Antigone Papavasiliou, MD         
Ippokratio General Hospital of Thessaloniki Recruiting
Thessaloniki, Greece, 54642
Principal Investigator: Dimitrios Zafeiriou, MD         
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         
Ireland
The Children's University Hospital Recruiting
Dublin, Ireland, D1
Contact: Declan O'Rourke    353 (1) 8784200    declan.orourke@cuh.ie   
Principal Investigator: Declan O'Rourke, 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         
Fondazione IRCCS Istituto Neurologico Carlo Besta Recruiting
Milano, Italy, 20133
Contact: Angela Pasquariello    390223942967    angela.pasquariello@istituto-besta.it   
Principal Investigator: Riccardo Masson, 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         
Uniwersyteckie Centrum Kliniczne Recruiting
Gdansk, Poland, 80-952
Principal Investigator: Maria Mazurkiewicz-Beldzinska, MD         
Russian Federation
Federal state budget educational institution of higher education "Russian national research medical university n.a. N.I. Pirogov" of Ministry of healthcare of Russian Federation Recruiting
Moscow, Russian Federation, 125412
Contact    7 (495) 483-72-50    niki@pedklin.ru   
Principal Investigator: Dmitry Vlodavets, MD, PhD         
Serbia
Clinic for Neurology and Psychiatry for Children and Youth Recruiting
Belgrade, Serbia, 11000
Contact: Biljana Milich    fax +381 11 2645064    biljana.milich@gmail.com   
Principal Investigator: Vedrana Milic Rasic, 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: Nuria Muelas, 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         
United Kingdom
Royal Hospital for Children (Glasgow) Recruiting
Glasgow, United Kingdom, G51 4TF
Contact: Lain Horrocks    44 (0)141 451 6527    iain.horrocks@ggc.scot.nhs.uk   
Principal Investigator: Lain Horrocks, MD         
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) 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         
John Radcliffe Hospital Recruiting
Oxford, United Kingdom, OX3 9DU
Contact: Sithara Ramdas    44 (0) 1865234188    sithara.ramdas@ouh.nhs.uk   
Principal Investigator: Sithara Ramdas, MD         
Sponsors and Collaborators
Sarepta Therapeutics, Inc.
Investigators
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Study Director: Medical Director Sarepta Therapeutics, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Sarepta Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02500381    
Other Study ID Numbers: 4045-301
First Posted: July 16, 2015    Key Record Dates
Last Update Posted: August 19, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked