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

A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study Assessing Safety, Tolerability, Pharmacodynamics, Efficacy, and Pharmacokinetics of DYNE-251 Administered to Participants With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping

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).

Study Overview

• Status: Active, not recruiting
• Conditions: Duchenne Muscular Dystrophy (DMD)
• Intervention / Treatment: Drug: Placebo; Drug: DYNE-251

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 02145
      • Children's Hospital at Westmead
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Murdoch Children's Research Institute
• Belgium
  • Gent, Belgium, 9000
    • UZ Gent
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Liège, Belgium, 4000
    • CHR Citadelle
• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, ON K1H 8L1
      • Children's Hospital of Eastern Ontario
• Ireland
  • Dublin, Ireland, D01 XD99
    • CHI [Children's Health Ireland] at Temple Street Children's University Hospital
• Italy
  • Lazio
    • Rome, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario A Gemelli
  • Lombardia
    • Milan, Lombardia, Italy, 20162
      • Fondazione Serena Onlus - CENTRO CLINICO NEMO
    • Milan, Lombardia, Italy, 20312
      • Ospedale San Raffaele S.r.l. - PPDS
• Korea, Republic of
  • Teugbyeolsi
    • Seoul, Teugbyeolsi, Korea, Republic of, 6351
      • Samsung Medical Center
• Spain
  • Barcelona, Spain, 8025
    • Hospital Universitario Vall d'Hebron - PPDS
  • Barcelona, Spain, 8950
    • Hospital Sant Joan de Déu Universidad de Barcelona
• United Kingdom
  • Bristol, United Kingdom, BS2 8BJ
    • Bristol Childrens Hospital
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital
  • Merseyside
    • Liverpool, Merseyside, United Kingdom, L12 2AP
      • Alder Hey Children's Hospital
  • Northumberland
    • Newcastle Upon Tyne, Northumberland, United Kingdom, NE1 4LP
      • Royal Victoria Infirmary
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS1 3EX
      • Leeds Teaching Hospitals NHS Trust
• United States
  • California
    • La Jolla, California, United States, 92037
      • University of California San Diego
    • Los Angeles, California, United States, 90095
      • UCLA University California of Los Angeles
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Rare Disease Research, LLC
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
  • Oregon
    • Portland, Oregon, United States, 97239
      • Shriners Hospitals for Children Portland
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224-1334
      • UPMC Children's Hospital of Pittsburgh
  • Utah
    • Salt Lake City, Utah, United States, 08412
      • University of UTAH - PPDS
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 16 years (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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).

Exclusion Criteria:

• 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.

Other inclusion and exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo-Controlled MAD Period - DYNE-251; DYNE-251 will be administered once every 4 weeks (Q4W) or once every 8 weeks (Q8W) over 24 weeks.	Drug: DYNE-251; Administered by IV infusion
Experimental: Placebo-Controlled MAD Period - Placebo; Placebo will be administered Q4W or Q8W over 24 weeks.	Drug: Placebo; Administered by IV infusion
Experimental: Open-Label and Long-Term Extension Period - DYNE-251; 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; Administered by IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Dystrophin Protein Levels in Muscle Tissue at Week 25	Baseline, Week 25
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Through study completion, up to Week 241

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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
Change From Baseline in Muscle Tissue PDPF at Week 49 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49		Baseline, Week 49
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 Blood CK Levels up to Week 241 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49		Baseline, up to Week 241
Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score in Ambulatory Participants up to Week 241	The NSAA is a 17-item functional scale used to measure functional motor abilities in ambulant participants with DMD and monitor progression of the disease and treatment effects in each of the items. The items are graded on a 3-point scale: 0=unable to achieve independently, 1=modified method but achieves goal with no physical assistance, and 2=normal, no obvious modification of activity. Total score range is 0 to 34.	Baseline, up to Week 241
Change From Baseline in Time to Rise From Floor in Ambulatory Participants up to Week 241		Baseline, up to Week 241
Change From Baseline in 10-Meter Run/Walk (10MRW) Time in Ambulatory Participants up to Week 241		Baseline, up to Week 241
Change From Baseline in Performance Upper Limb (PUL) Scale Version 2.0 Score up to Week 241	The PUL scale is a validated tool specifically designed for assessing upper limb function in ambulant and non-ambulant individuals with DMD. It includes an entry item to define the broad starting functional level and 22 items subdivided into 3 areas indicative of upper limb strength as, shoulder level, midlevel, and distal level. The global score is a combination of the 3 areas and ranges from 0 to 42. Lower scores indicate higher disability.	Baseline, up to Week 241
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) up to Week 241		Baseline, up to Week 241
Change From Baseline in Stride Velocity 95th Centile (SV95C) in Ambulatory Participants up to Week 241		Baseline, up to Week 241
Maximum Observed Plasma Drug Concentration of DYNE-251 (Cmax)		Through study completion, up to Week 241
Time to Maximum Observed Plasma Drug Concentration of DYNE-251 (tmax)		Through study completion, up to Week 241
Area Under the Plasma Drug Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration of DYNE-251 in Plasma (AUC0-tlast)		Through study completion, up to Week 241
Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 (Dosing) Extrapolated to Time Infinity of DYNE-251 (AUC∞)		Through study completion, up to Week 241
Apparent Terminal Phase Elimination Rate Constant of DYNE-251 in Plasma (λz)		Through study completion, up to Week 241
Apparent Terminal Elimination Half-Life of DYNE-251 in Plasma (t½)		Through study completion, up to Week 241
Total Body Clearance (CL) of DYNE-251		Through study completion, up to Week 241
Volume of Distribution at the Terminal Phase of DYNE-251 in Plasma (Vz)		Through study completion, up to Week 241
Volume of Distribution at Steady State of DYNE-251 in Plasma (Vss)		Through study completion, up to Week 241
Tissue Phosphorodiamidate Morpholino Oligomer (PMO) Concentration of DYNE-251 in Muscle Tissue		Through study completion, up to Week 241
Percentage of Participants With Antidrug Antibodies (ADAs)		Through study completion, up to Week 241

Collaborators and Investigators

• Sponsor: Dyne Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2022
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): November 1, 2029

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 11, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: DYNE251-DMD-201; 2023-510351-31-00 (Ctis); ITA 362546 (model PA-000798) (Other Identifier: Health Canada Investigational Testing Authorization (ITA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No