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

NCT02500381 | Completed Phase 3 DMC FDA Drug

• 3 other identifiers: 4045-3012015-002069-522024-514698-23-00
• Study Type: interventional
• Target: 228
• Locations: 23 countries
• Sites: 75

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.

Conditions

Duchenne Muscular Dystrophy

Keywords

Duchenne muscular dystrophy; Exon Skipping; DMD; Exon 53; Exon 45; Ambulatory; Pediatric; Duchenne

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in the 4-Step Ascend Velocity at Week 96

  Baseline, Week 96

Secondary Outcomes (7)

• Change from Baseline in the Total Distance Walked During 6MWT at Week 96

  Baseline, Week 96

• Change from Baseline in Rise from Floor Velocity at Week 96

  Baseline, Week 96

• Change From Baseline in the 4-Step Ascend Velocity at Week 144

  Baseline, Week 144

• Change From Baseline in Total Distance Walked During the 10-meter walk/run (10-MWR) Velocity

  Baseline, Week 96

• Change From Baseline in the North Star Ambulatory Assessment (NSAA) Total Score at Week 96

  Baseline, Week 96

Study Arms (3)

SRP-4045

EXPERIMENTAL

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-4053

EXPERIMENTAL

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

Placebo followed by SRP-4045 or SRP-4053

PLACEBO COMPARATOR

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; Drug: SRP-4053; Drug: Placebo

Interventions

SRP-4045 DRUG

SRP-4045 solution for IV infusion

Also known as: Casimersen, AMONDYS 45

Placebo followed by SRP-4045 or SRP-4053; SRP-4045

SRP-4053 DRUG

SRP-4053 solution for IV infusion

Also known as: Golodirsen, VYONDYS 53

Placebo followed by SRP-4045 or SRP-4053; SRP-4053

Placebo DRUG

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

Placebo followed by SRP-4045 or SRP-4053

Eligibility Criteria

• Age: 6 Years - 13 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sarepta Therapeutics, Inc.: lead

Study Sites (76)

Neuromuscular Research Center

Phoenix, Arizona, 85028, United States

Location

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

David Geffen School of Medicine, UCLA

Los Angeles, California, 90095, United States

Location

Rady Children's Hospital San Diego/ UCSD

San Diego, California, 92123, United States

Location

Stanford University School of Medicine/Medical Center

Stanford, California, 94305, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

NW Florida Clinical Research Group, LLC

Gulf Breeze, Florida, 32561, United States

Location

Center for Integrative Rare Disease Research (CIRDR)

Atlanta, Georgia, 30318, United States

Location

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

Chicago, Illinois, 60611, United States

Location

University of Iowa Children's Hospital

Iowa City, Iowa, 52242, United States

Location

University of Kansas, Medical Center

Kansas City, Kansas, 66160, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Las Vegas Clinic

Las Vegas, Nevada, 89145, United States

Location

University of Rochester Clinical Research Center

Rochester, New York, 14642, United States

Location

Cincinnati Children's Hospital Medical Center (CCHMC)

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Shriners Hospital for Children

Portland, Oregon, 97239, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Children's Medical Center Dallas

Dallas, Texas, 75235, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Children's Hospital of the King's Daughters

Norfolk, Virginia, 23507, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

DOM Centro de Reumatologia

Buenos Aires, 1111, Argentina

Location

Royal Children's Hospital Melbourne

Parkville, Victoria, 3052, Australia

Location

Queensland Children's Hospital

South Brisbane, 4101, Australia

Location

Children's Hospital at Westmead

Westmead, 2145, Australia

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Universitair Ziekenhuis Leuven

Leuven, 3000, Belgium

Location

CHR de la Citadelle

Liège, 4000, Belgium

Location

University Multiprofile Hospital for Active Treatment Aleksandrovska EAD

Sofia, Sofia-Grad, 1431, Bulgaria

Location

Alberta Childrens Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

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

Vancouver, British Columbia, V6H 3V4, Canada

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

University Hospital Brno

Brno, 61300, Czechia

Location

Fakultni nemocnice v Motole

Prague, 15008, Czechia

Location

Rigshospitalet Copenhagen University Hospital

København Ø, 2100, Denmark

Location

Hôpital Des Enfants

Toulouse, Haute-Garonne, 31059, France

Location

Reference Centre for Neuromuscular Diseases

Nantes, 44093, France

Location

Hôpital Armand Trousseau

Paris, 75012, France

Location

LMU Klinikum der Universität

München, Bavaria, 80337, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, 13353, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

University Hospital Freiburg

Freiburg im Breisgau, 79106, Germany

Location

IASO Children's Hospital

Marousi, 15123, Greece

Location

Ippokratio General Hospital of Thessaloniki

Thessaloniki, 54642, Greece

Location

Semmelweis Egyetem Genomikai Medicina és Ritka Betegsegek Intezete

Budapest, 1083, Hungary

Location

Royal Instituite of Child Neurosciences

Ahmedabad, Gujarat, 380054, India

Location

Deenanth Mangeshkar Hospital

Pune, Maharashtra, 411004, India

Location

The Children's University Hospital

Dublin, D1, Ireland

Location

Schneider Children's Medical Center of Israel

Petah Tikvah, 49102, Israel

Location

Azienda Ospedaliero-Universitaria di Ferrara - Arcispedale Sant' Anna

Ferrara, 44124, Italy

Location

Istituto Giannina Gaslini

Genoa, 16147, Italy

Location

Az Ospedaliera Universitaria Policlinico G Martino

Messina, 98125, Italy

Location

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133, Italy

Location

Policlinico Universitario A Gemelli

Rome, 00168, Italy

Location

Neurociencias Estudios Clínicos S.C

Culiacán, 80020, Mexico

Location

Instituto de Investigaciones Clínicas para la Salud A.C

Durango, 34000, Mexico

Location

Samodzielny Publiczny Centralny Szpital Kliniczny

Warsaw, Masovian Voivodeship, 02-097, Poland

Location

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-952, Poland

Location

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, 125412, Russia

Location

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

Yekaterinburg, Russia

Location

Clinic for Neurology and Psychiatry for Children and Youth

Belgrade, 11000, Serbia

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Pusan National University Yangsan Hospital

Yangsan, 50612, South Korea

Location

Hospital de La Santa Creu i Sant Pau

Barcelona, 08041, Spain

Location

Hospital Sant Joan de Deu

Barcelona, 08950, Spain

Location

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, Spain

Location

Drottning Silvias Barn Och Ungdomssjukhus

Gothenburg, SE-41685, Sweden

Location

Royal Hospital for Children (Glasgow)

Glasgow, G51 4TF, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, LS1 3EX, United Kingdom

Location

Alder Hey Childrens Hospital

Liverpool, L12 2AP, United Kingdom

Location

Great Ormond Street Hospital (GOSH)

London, WC1N 1EH, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

John Radcliffe Hospital

Oxford, OX3 9DU, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 40098309 DERIVED

• 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.

  PMID: 34105177 DERIVED

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

casimersen; golodirsen

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Medical Director

  Sarepta Therapeutics, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Part 1 is double-blind and randomized; Part 2 is open-label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 14, 2015
• First Posted: July 16, 2015
• Study Start: September 28, 2016
• Primary Completion: November 12, 2024
• Study Completion: October 16, 2025
• Last Updated: November 18, 2025

Record last verified: 2025-11

Locations

CA (4); AU (3); BE (3); KR (2); US (23); IT (5); IL (1); DK (1); HU (1); ES (3); PL (2); BU (1); ME (2); SE (1); FR (3); IE (1); AR (1); CZ (2); RU (2); GB (6); DE (4); GR (2); IN (2)