Duchenne Muscular Dystrophy (DMD)Phase 1/2DELIVERNCT05524883
Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-251 in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping
A Phase 1/2 study testing DYNE-251 in people with Duchenne Muscular Dystrophy (DMD), run by Dyne Therapeutics at 30 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 16 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy (DMD)
- What is being tested?
- DYNE-251
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 30 sitesin 9 countries
- Study dates
- 12 Aug 2022to Sep 2031
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 16 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
30 sites in 9 countries.
30 sites in 9 countries
United States11 sites
Rare Disease Research, LLC
Atlanta, Georgia, 30329
Children's Hospital Colorado
Aurora, Colorado, 80045
Nationwide Children's Hospital
Columbus, Ohio, 43205
University of California San Diego
La Jolla, California, 92037
UCLA University California of Los Angeles
Los Angeles, California, 90095
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224-1334
Shriners Hospitals for Children Portland
Portland, Oregon, 97239
Virginia Commonwealth University
Richmond, Virginia, 23219
University of Utah - PPDS
Salt Lake City, Utah, 08412
UMass Memorial Medical Center
Worcester, Massachusetts, 01655
United Kingdom5 sites
Bristol Childrens Hospital
Bristol, BS2 8BJ
Leeds Teaching Hospitals NHS Trust
Leeds, West Yorkshire, LS1 3EX
Alder Hey Children's Hospital
Liverpool, Merseyside, L12 2AP
Great Ormond Street Hospital
London, WC1N 3JH
Royal Victoria Infirmary
Newcastle upon Tyne, Northumberland, NE1 4LP
Belgium3 sites
UZ Gent
Ghent, 9000
UZ Leuven
Leuven, 3000
CHR Citadelle
Liège, 4000
Italy3 sites
Fondazione Serena Onlus - Centro Clinico NeMO
Milan, Lombardy, 20162
Ospedale San Raffaele S.r.l. - PPDS
Milan, Lombardy, 20312
Fondazione Policlinico Universitario A Gemelli
Rome, Lazio, 00168
Australia2 sites
Murdoch Children's Research Institute
Parkville, Victoria, 3052
Children's Hospital at Westmead
Westmead, New South Wales, 02145
Canada2 sites
London Health Sciences Centre
London, Ontario, N6A 5W9
Children's Hospital of Eastern Ontario
Ottawa, Ontario, ON K1H 8L1
Spain2 sites
Hospital Universitario Vall d'Hebron - PPDS
Barcelona, 8025
Hospital Sant Joan de Déu Universidad de Barcelona
Barcelona, 8950
Ireland1 site
CHI [Children's Health Ireland] at Temple Street Children's University Hospital
Dublin, D01 XD99
About this study
Official title: 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 (288 weeks).
- Conditions
- Duchenne Muscular Dystrophy (DMD)
- Being tested
- DYNE-251, Placebo
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DYNE-251Drug
Administered by IV infusion
PlaceboDrug
Administered by IV infusion
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: DYNE-251 |
| Placebo-Controlled MAD Period - Placebo | Experimental | Placebo will be administered Q4W or Q8W over 24 weeks. Receives: Drug: Placebo |
| Open-Label and Long-Term Extension Period - DYNE-251 | Experimental | DYNE-251 will be administered Q4W or Q8W for up to 288 weeks after participants complete the Placebo-Controlled MAD Period of the study. Receives: Drug: DYNE-251 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Measured: Through study completion, up to Week 337
Change From Baseline in Dystrophin Protein Levels in Muscle Tissue at Week 25
Measured: 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
Measured: 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
Measured: Baseline, Week 25
Change From Baseline in Blood Creatine Kinase (CK) Levels up to Week 337 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25
Measured: Baseline, up to Week 337
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
Measured: 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
Measured: 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
Measured: Baseline, Week 49
Change From Baseline in Blood CK Levels up to Week 337 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49
Measured: Baseline, up to Week 337
Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score in Ambulatory Participants up to Week 337
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.
Measured: Baseline, up to Week 337
Change From Baseline in Time to Rise From Floor in Ambulatory Participants up to Week 337
Measured: Baseline, up to Week 337
Change From Baseline in 10-Meter Run/Walk (10MRW) Time in Ambulatory Participants up to Week 337
Measured: Baseline, up to Week 337
Change From Baseline in Performance Upper Limb (PUL) Scale Version 2.0 Score up to Week 337
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.
Measured: Baseline, up to Week 337
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) up to Week 337
Measured: Baseline, up to Week 337
Change From Baseline in Stride Velocity 95th Centile (SV95C) in Ambulatory Participants up to Week 337
Measured: Baseline, up to Week 337
Maximum Observed Plasma Drug Concentration of DYNE-251 (Cmax)
Measured: Through study completion, up to Week 337
Time to Maximum Observed Plasma Drug Concentration of DYNE-251 (tmax)
Measured: Through study completion, up to Week 337
Area Under the Plasma Drug Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration of DYNE-251 in Plasma (AUC0-tlast)
Measured: Through study completion, up to Week 337
Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 (Dosing) Extrapolated to Time Infinity of DYNE-251 (AUC∞)
Measured: Through study completion, up to Week 337
Apparent Terminal Phase Elimination Rate Constant of DYNE-251 in Plasma (λz)
Measured: Through study completion, up to Week 337
Apparent Terminal Elimination Half-Life of DYNE-251 in Plasma (t½)
Measured: Through study completion, up to Week 337
Total Body Clearance (CL) of DYNE-251
Measured: Through study completion, up to Week 337
Volume of Distribution at the Terminal Phase of DYNE-251 in Plasma (Vz)
Measured: Through study completion, up to Week 337
Volume of Distribution at Steady State of DYNE-251 in Plasma (Vss)
Measured: Through study completion, up to Week 337
Tissue Phosphorodiamidate Morpholino Oligomer (PMO) Concentration of DYNE-251 in Muscle Tissue
Measured: Through study completion, up to Week 337
Incidence of Antidrug Antibodies (ADAs)
Measured: Through study completion, up to Week 337
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2022
- Study start12 Aug 2022
- Primary completionSep 2031 (estimated)
- Study completionSep 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Duchenne Muscular Dystrophy (DMD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dyne Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05524883
- Sponsor's protocol ID
- DYNE251-DMD-201
- Other IDs
- 2023-510351-31-00, ITA 362546 (model PA-000798), 2023
- Acronym
- DELIVER
- Status last verified
- Aug 2026
- First submitted
- 30 Aug 2022
- Last updated
- 11 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No