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Trial record 1 of 1 for:    NCT02500381
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Study of SRP-4045 (Casimersen) and SRP-4053 (Golodirsen) in Participants With Duchenne Muscular Dystrophy (DMD) (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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02500381
Recruitment Status : Active, not recruiting
First Posted : July 16, 2015
Last Update Posted : January 19, 2023
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 (casimersen) and SRP-4053 (golodirsen) 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)
Actual Enrollment : 229 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


Locations
Hide Hide 75 study locations
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United States, Arizona
Neuromuscular Research Center
Phoenix, Arizona, United States, 85028
United States, California
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
David Geffen School of Medicine, UCLA
Los Angeles, California, United States, 90095
Rady Children's Hospital San Diego/ UCSD
San Diego, California, United States, 92123
Stanford University School of Medicine/Medical Center
Stanford, California, United States, 94305
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
NW Florida Clinical Research Group, LLC
Gulf Breeze, Florida, United States, 32561
United States, Georgia
Center for Integrative Rare Disease Research (CIRDR)
Atlanta, Georgia, United States, 30318
United States, Illinois
Ann and Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, United States, 60611
United States, Iowa
University of Iowa Children's Hospital
Iowa City, Iowa, United States, 52242
United States, Kansas
University of Kansas, Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
United States, Missouri
St. Louis Children's Hospital
Saint Louis, Missouri, United States, 63110
United States, Nevada
Las Vegas Clinic
Las Vegas, Nevada, United States, 89145
United States, New York
University of Rochester Clinical Research Center
Rochester, New York, United States, 14642
United States, Ohio
Cincinnati Children's Hospital Medical Center (CCHMC)
Cincinnati, Ohio, United States, 45229
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Oregon
Shriners Hospital for Children
Portland, Oregon, United States, 97239
United States, Pennsylvania
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, United States, 15224
United States, Texas
Children's Medical Center Dallas
Dallas, Texas, United States, 75235
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Virginia
Children's Hospital of the King's Daughters
Norfolk, Virginia, United States, 23507
United States, Wisconsin
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Argentina
DOM Centro de Reumatologia
Ciudad Autonoma de Buenos Aires, Argentina, 1111
Australia, Victoria
Royal Children's Hospital Melbourne
Parkville, Victoria, Australia, 3052
Australia
Queensland Children's Hospital
South Brisbane, Australia, 4101
Children's Hospital at Westmead
Westmead, Australia, 2145
Belgium
Universitair Ziekenhuis Gent
Ghent, Belgium, 9000
Universitair Ziekenhuis Leuven
Leuven, Belgium, 3000
CHR de la Citadelle
Liège, Belgium, 4000
Bulgaria
University Multiprofile Hospital for Active Treatment Aleksandrovska EAD
Sofia, Sofia-Grad, Bulgaria, 1431
Canada, Alberta
Alberta Childrens Hospital
Calgary, Alberta, Canada, T3B 6A8
Canada, British Columbia
Children's and Women's Health Centre of British Columbia
Vancouver, British Columbia, Canada, V6H 3V4
Canada, Ontario
London Health Sciences Centre
London, Ontario, Canada, N6A 5W9
Children's Hospital of Eastern Ontario
Ottawa, Ontario, Canada, K1H 8L1
Czechia
University Hospital Brno
Brno, Czechia, 61300
Fakultni nemocnice v Motole
Praha, Czechia, 15008
Denmark
Rigshospitalet Copenhagen University Hospital
København Ø, Denmark, 2100
France
Hôpital Des Enfants
Toulouse, Haute-Garonne, France, 31059
Reference Centre for Neuromuscular Diseases
Nantes, France, 44093
Hôpital Armand Trousseau
Paris, France, 75012
Germany
Charité - Universitätsmedizin Berlin
Berlin, Germany, 13353
Universitätsklinikum Essen
Essen, Germany, 45122
University Hospital Freiburg
Freiburg, Germany, 79106
Greece
IASO Children's Hospital
Maroussi, Greece, 15123
Ippokratio General Hospital of Thessaloniki
Thessaloniki, Greece, 54642
Hungary
Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete
Budapest, Hungary, 1083
India
Royal Instituite of Child Neurosciences
Ahmedabad, Gujarat, India, 380054
Deenanth Mangeshkar Hospital
Pune, Maharashtra, India, 411004
Ireland
The Children's University Hospital
Dublin, Ireland, D1
Israel
Schneider Children's Medical Center of Israel
Petah Tikvah, Israel, 49102
Italy
Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant' Anna
Ferrara, Italy, 44124
Istituto Giannina Gaslini
Genoa, Italy, 16147
Az Ospedaliera Universitaria Policlinico G Martino
Messina, Italy, 98125
Fondazione IRCCS Istituto Neurologico Carlo Besta
Milano, Italy, 20133
Policlinico Universitario A Gemelli
Rome, Italy, 00168
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Pusan National University Yangsan Hospital
Yangsan, Korea, Republic of, 50612
Mexico
Neurociencias Estudios Clínicos S.C
Culiacán, Mexico, 80020
Instituto de Investigaciones Clínicas para la Salud A.C
Durango, Mexico, 34000
Poland
Samodzielny Publiczny Centralny Szpital Kliniczny
Warsaw, Mazowieckie, Poland, 02-097
Uniwersyteckie Centrum Kliniczne
Gdansk, Poland, 80-952
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
Moscow, Russian Federation, 125412
State Autonomous Healthcare Institution of Sverdlovsk Region Children's Clinical Hospital No. 9 City of Ekaterinburg
Yekaterinburg, Russian Federation
Serbia
Clinic for Neurology and Psychiatry for Children and Youth
Belgrade, Serbia, 11000
Spain
Hospital de La Santa Creu i Sant Pau
Barcelona, Spain, 08041
Hospital Sant Joan de Deu
Barcelona, Spain, 08950
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, Spain
Sweden
Drottning Silvias Barn Och Ungdomssjukhus
Göteborg, Sweden, SE-41685
United Kingdom
Royal Hospital for Children (Glasgow)
Glasgow, United Kingdom, G51 4TF
Leeds Teaching Hospitals NHS Trust
Leeds, United Kingdom, LS1 3EX
Alder Hey Childrens Hospital
Liverpool, United Kingdom, L12 2AP
Great Ormond Street Hospital (GOSH)
London, United Kingdom, WC1N 1EH
Royal Victoria Infirmary
Newcastle upon Tyne, United Kingdom, NE1 4LP
John Radcliffe Hospital
Oxford, United Kingdom, OX3 9DU
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: January 19, 2023
Last Verified: January 2023
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