Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-251 in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping

NCT05524883 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: DYNE251-DMD-2012023-510351-31-00ITA 362546 (model PA-000798)
• Study Type: interventional
• Target: 86
• Locations: 9 countries
• Sites: 30

Brief Summary

The primary purpose of this study is to evaluate the safety, tolerability, and dystrophin protein levels in muscle tissue following multiple intravenous (IV) doses of DYNE-251 in participants with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. The study consists of 3 periods: a multiple-ascending dose (MAD) / placebo-controlled period (24 weeks), an open-label period (24 weeks) and a long-term extension (LTE) period (192 weeks).

Conditions

Duchenne Muscular Dystrophy (DMD)

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Through study completion, up to Week 241

• Change From Baseline in Dystrophin Protein Levels in Muscle Tissue at Week 25

  Baseline, Week 25

Secondary Outcomes (24)

• Change From Baseline in Muscle Tissue Exon 51 Skipping Levels at Week 25 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25

  Baseline, Week 25

• Change From Baseline in Muscle Tissue Percent Dystrophin-Positive Fiber (PDPF) at Week 25 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25

  Baseline, Week 25

• Change From Baseline in Blood Creatine Kinase (CK) Levels up to Week 241 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25

  Baseline, up to Week 241

• Change From Baseline in Dystrophin Protein Level in Muscle Tissue as Determined by Western Blot at Week 49 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49

  Baseline, Week 49

• Change From Baseline in Muscle Tissue Exon 51 Skipping Levels at Week 49 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49

  Baseline, Week 49

Study Arms (3)

Placebo-Controlled MAD Period - DYNE-251

EXPERIMENTAL

DYNE-251 will be administered once every 4 weeks (Q4W) or once every 8 weeks (Q8W) over 24 weeks.

Drug: DYNE-251

Placebo-Controlled MAD Period - Placebo

EXPERIMENTAL

Placebo will be administered Q4W or Q8W over 24 weeks.

Drug: Placebo

Open-Label and Long-Term Extension Period - DYNE-251

EXPERIMENTAL

DYNE-251 will be administered Q4W or Q8W for up to 192 weeks after participants complete the Placebo-Controlled MAD Period of the study.

Drug: DYNE-251

Interventions

DYNE-251 DRUG

Administered by IV infusion

Open-Label and Long-Term Extension Period - DYNE-251; Placebo-Controlled MAD Period - DYNE-251

Placebo DRUG

Administered by IV infusion

Placebo-Controlled MAD Period - Placebo

Eligibility Criteria

• Age: 4 Years - 16 Years
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 4 to 16 years inclusive, at the time of informed consent/assent.
• Male with a confirmed diagnosis of DMD and with a mutation in the dystrophin gene characterized by exon deletion amenable to exon 51 skipping.
• Upper extremity muscle group that is amenable to muscle biopsy.
• Brooke Upper Extremity Scale score of 1 or 2.
• Ambulatory or non-ambulatory. A non-ambulatory participant must have been non-ambulatory for \<2 years before enrollment.
• Receiving a stable dosage of glucocorticoids for at least 12 weeks prior to the start of study drug administration, with the expectation of maintaining a stable dose during the Placebo-Controlled and Open-Label Periods of the study (unless dose adjustment is required by weight change).
• Left ventricular ejection fraction of ≥50% by echocardiogram or ≥55% by cardiac magnetic resonance imaging (MRI).

You may not qualify if:

• Uncontrolled clinical symptoms and signs of congestive heart failure (CHF).
• Any change in prophylaxis/treatment for CHF within 3 months prior to the start of study treatment.
• History of major surgical procedure within 12 weeks prior to the start of study drug administration or an expectation of a major surgical procedure during the study.
• Requirement of daytime ventilator assistance.
• Percent predicted FVC \<40 % (applies only for participants who are age ≥7 years).
• Receipt of eteplirsen, or alternative exon-skipping/dystrophin-modifying therapy, within 12 weeks of randomization.
• Receipt of non-exon skipping investigational drug within 4 months before the start of study drug administration.
• Receipt of gene therapy at any time.

Sponsors & Collaborators

• Dyne Therapeutics: lead

Study Sites (30)

University of California San Diego

La Jolla, California, 92037, United States

Location

UCLA University California of Los Angeles

Los Angeles, California, 90095, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Rare Disease Research, LLC

Atlanta, Georgia, 30329, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Shriners Hospitals for Children Portland

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224-1334, United States

Location

University of Utah - PPDS

Salt Lake City, Utah, 08412, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

Children's Hospital at Westmead

Westmead, New South Wales, 02145, Australia

Location

Murdoch Children's Research Institute

Parkville, Victoria, 3052, Australia

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven

Leuven, 3000, Belgium

Location

CHR Citadelle

Liège, 4000, Belgium

Location

London Health Sciences Centre

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, ON K1H 8L1, Canada

Location

CHI [Children's Health Ireland] at Temple Street Children's University Hospital

Dublin, D01 XD99, Ireland

Location

Fondazione Policlinico Universitario A Gemelli

Rome, Lazio, 00168, Italy

Location

Fondazione Serena Onlus - Centro Clinico NeMO

Milan, Lombardy, 20162, Italy

Location

Ospedale San Raffaele S.r.l. - PPDS

Milan, Lombardy, 20312, Italy

Location

Samsung Medical Center

Seoul, Teugbyeolsi, 6351, South Korea

Location

Hospital Universitario Vall d'Hebron - PPDS

Barcelona, 8025, Spain

Location

Hospital Sant Joan de Déu Universidad de Barcelona

Barcelona, 8950, Spain

Location

Alder Hey Children's Hospital

Liverpool, Merseyside, L12 2AP, United Kingdom

Location

Royal Victoria Infirmary

Newcastle upon Tyne, Northumberland, NE1 4LP, United Kingdom

Location

Leeds Teaching Hospitals NHS Trust

Leeds, West Yorkshire, LS1 3EX, United Kingdom

Location

Bristol Childrens Hospital

Bristol, BS2 8BJ, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

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 Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2022
• First Posted: September 1, 2022
• Study Start: August 12, 2022
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2029
• Last Updated: August 13, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (11); AU (2); IE (1); IT (3); ES (2); BE (3); CA (2); GB (5); KR (1)