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

NCT ID: NCT02500381

Last Updated: 2025-11-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

228 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-28

Study Completion Date

2025-10-16

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Duchenne Muscular Dystrophy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Part 1 is double-blind and randomized; Part 2 is open-label.

Study Groups

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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).

Group Type EXPERIMENTAL

SRP-4045

Intervention Type DRUG

SRP-4045 solution for IV infusion

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).

Group Type EXPERIMENTAL

SRP-4053

Intervention Type DRUG

SRP-4053 solution for IV infusion

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).

Group Type PLACEBO_COMPARATOR

SRP-4045

Intervention Type DRUG

SRP-4045 solution for IV infusion

SRP-4053

Intervention Type DRUG

SRP-4053 solution for IV infusion

Placebo

Intervention Type DRUG

SRP-4045 or SRP-4053 placebo-matching solution for IV infusion

Interventions

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SRP-4045

SRP-4045 solution for IV infusion

Intervention Type DRUG

SRP-4053

SRP-4053 solution for IV infusion

Intervention Type DRUG

Placebo

SRP-4045 or SRP-4053 placebo-matching solution for IV infusion

Intervention Type DRUG

Other Intervention Names

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Casimersen AMONDYS 45 Golodirsen VYONDYS 53

Eligibility Criteria

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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 brachii muscles or 2 alternative upper arm 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
Minimum Eligible Age

6 Years

Maximum Eligible Age

13 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Sarepta Therapeutics, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Sarepta Therapeutics, Inc.

Locations

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Neuromuscular Research Center

Phoenix, Arizona, United States

Site Status

Children's Hospital Los Angeles

Los Angeles, California, United States

Site Status

David Geffen School of Medicine, UCLA

Los Angeles, California, United States

Site Status

Rady Children's Hospital San Diego/ UCSD

San Diego, California, United States

Site Status

Stanford University School of Medicine/Medical Center

Stanford, California, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

NW Florida Clinical Research Group, LLC

Gulf Breeze, Florida, United States

Site Status

Center for Integrative Rare Disease Research (CIRDR)

Atlanta, Georgia, United States

Site Status

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status

University of Iowa Children's Hospital

Iowa City, Iowa, United States

Site Status

University of Kansas, Medical Center

Kansas City, Kansas, United States

Site Status

Boston Children's Hospital

Boston, Massachusetts, United States

Site Status

St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status

Las Vegas Clinic

Las Vegas, Nevada, United States

Site Status

University of Rochester Clinical Research Center

Rochester, New York, United States

Site Status

Cincinnati Children's Hospital Medical Center (CCHMC)

Cincinnati, Ohio, United States

Site Status

Nationwide Children's Hospital

Columbus, Ohio, United States

Site Status

Shriners Hospital for Children

Portland, Oregon, United States

Site Status

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Children's Medical Center Dallas

Dallas, Texas, United States

Site Status

University of Utah

Salt Lake City, Utah, United States

Site Status

Children's Hospital of the King's Daughters

Norfolk, Virginia, United States

Site Status

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

DOM Centro de Reumatologia

Buenos Aires, , Argentina

Site Status

Royal Children's Hospital Melbourne

Parkville, Victoria, Australia

Site Status

Queensland Children's Hospital

South Brisbane, , Australia

Site Status

Children's Hospital at Westmead

Westmead, , Australia

Site Status

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status

Universitair Ziekenhuis Leuven

Leuven, , Belgium

Site Status

CHR de la Citadelle

Liège, , Belgium

Site Status

University Multiprofile Hospital for Active Treatment Aleksandrovska EAD

Sofia, Sofia-Grad, Bulgaria

Site Status

Alberta Childrens Hospital

Calgary, Alberta, Canada

Site Status

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

Vancouver, British Columbia, Canada

Site Status

London Health Sciences Centre

London, Ontario, Canada

Site Status

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Site Status

University Hospital Brno

Brno, , Czechia

Site Status

Fakultni nemocnice v Motole

Prague, , Czechia

Site Status

Rigshospitalet Copenhagen University Hospital

København Ø, , Denmark

Site Status

Hôpital Des Enfants

Toulouse, Haute-Garonne, France

Site Status

Reference Centre for Neuromuscular Diseases

Nantes, , France

Site Status

Hôpital Armand Trousseau

Paris, , France

Site Status

LMU Klinikum der Universität

München, Bavaria, Germany

Site Status

Charité - Universitätsmedizin Berlin

Berlin, , Germany

Site Status

Universitätsklinikum Essen

Essen, , Germany

Site Status

University Hospital Freiburg

Freiburg im Breisgau, , Germany

Site Status

IASO Children's Hospital

Marousi, , Greece

Site Status

Ippokratio General Hospital of Thessaloniki

Thessaloniki, , Greece

Site Status

Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete

Budapest, , Hungary

Site Status

Royal Instituite of Child Neurosciences

Ahmedabad, Gujarat, India

Site Status

Deenanth Mangeshkar Hospital

Pune, Maharashtra, India

Site Status

The Children's University Hospital

Dublin, , Ireland

Site Status

Schneider Children's Medical Center of Israel

Petah Tikvah, , Israel

Site Status

Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant' Anna

Ferrara, , Italy

Site Status

Istituto Giannina Gaslini

Genoa, , Italy

Site Status

Az Ospedaliera Universitaria Policlinico G Martino

Messina, , Italy

Site Status

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, , Italy

Site Status

Policlinico Universitario A Gemelli

Rome, , Italy

Site Status

Neurociencias Estudios Clínicos S.C

Culiacán, , Mexico

Site Status

Instituto de Investigaciones Clínicas para la Salud A.C

Durango, , Mexico

Site Status

Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, Masovian Voivodeship, Poland

Site Status

Uniwersyteckie Centrum Kliniczne

Gdansk, , Poland

Site Status

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, , Russia

Site Status

State Autonomous Healthcare Institution of Sverdlovsk Region Children's Clinical Hospital No. 9 City of Ekaterinburg

Yekaterinburg, , Russia

Site Status

Clinic for Neurology and Psychiatry for Children and Youth

Belgrade, , Serbia

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Pusan National University Yangsan Hospital

Yangsan, , South Korea

Site Status

Hospital de La Santa Creu i Sant Pau

Barcelona, , Spain

Site Status

Hospital Sant Joan de Deu

Barcelona, , Spain

Site Status

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Site Status

Drottning Silvias Barn Och Ungdomssjukhus

Gothenburg, , Sweden

Site Status

Royal Hospital for Children (Glasgow)

Glasgow, , United Kingdom

Site Status

Leeds Teaching Hospitals NHS Trust

Leeds, , United Kingdom

Site Status

Alder Hey Childrens Hospital

Liverpool, , United Kingdom

Site Status

Great Ormond Street Hospital (GOSH)

London, , United Kingdom

Site Status

Royal Victoria Infirmary

Newcastle upon Tyne, , United Kingdom

Site Status

John Radcliffe Hospital

Oxford, , United Kingdom

Site Status

Countries

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United States Argentina Australia Belgium Bulgaria Canada Czechia Denmark France Germany Greece Hungary India Ireland Israel Italy Mexico Poland Russia Serbia South Korea Spain Sweden United Kingdom

References

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Vandekerckhove I, Hanssen B, Peeters N, Dewit T, De Beukelaer N, Van den Hauwe M, De Waele L, Van Campenhout A, De Groote F, Desloovere K. Anthropometric-related percentile curves for muscle size and strength of lower limb muscles of typically developing children. J Anat. 2025 Aug;247(2):348-362. doi: 10.1111/joa.14241. Epub 2025 Mar 17.

Reference Type DERIVED
PMID: 40098309 (View on PubMed)

Wagner KR, Kuntz NL, Koenig E, East L, Upadhyay S, Han B, Shieh PB. Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: A randomized, double-blind, placebo-controlled, dose-titration trial. Muscle Nerve. 2021 Sep;64(3):285-292. doi: 10.1002/mus.27347. Epub 2021 Jun 29.

Reference Type DERIVED
PMID: 34105177 (View on PubMed)

Other Identifiers

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4045-301

Identifier Type: -

Identifier Source: org_study_id

2015-002069-52

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2024-514698-23-00

Identifier Type: OTHER

Identifier Source: secondary_id

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