Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-251 in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping (DELIVER)
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|ClinicalTrials.gov Identifier: NCT05524883|
Recruitment Status : Recruiting
First Posted : September 1, 2022
Last Update Posted : May 6, 2023
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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 period (96 weeks).
|Condition or disease||Intervention/treatment||Phase|
|Duchenne Muscular Dystrophy (DMD)||Drug: DYNE-251 Drug: Placebo||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||48 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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|
|Actual Study Start Date :||August 12, 2022|
|Estimated Primary Completion Date :||November 2026|
|Estimated Study Completion Date :||November 2026|
Experimental: Placebo-Controlled MAD Period - DYNE-251
DYNE-251 will be administered 6 times over 24 weeks.
Administered by IV infusion, every 4 weeks
Experimental: Placebo-Controlled MAD Period - Placebo
Placebo will be administered 6 times over 24 weeks.
Administered by IV infusion, every 4 weeks
Experimental: Open-Label and Long-Term Extension Period - DYNE-251
DYNE-251 will be administered up to 30 times (over 120 weeks) after participants complete the Placebo-Controlled MAD Period of the study.
Administered by IV infusion, every 4 weeks
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Through study completion, up to Week 145 ]
- Change From Baseline in Dystrophin Protein Levels in Muscle Tissue at Week 25 [ Time Frame: Baseline, Week 25 ]
- Change From Baseline in Muscle Tissue Exon 51 Skipping Levels at Week 25 [ Time Frame: Baseline, Week 25 ]
- Change From Baseline in Muscle Tissue Percent Dystrophin-Positive Fiber (PDPF) at Week 25 [ Time Frame: Baseline, Week 25 ]
- Change From Baseline in Blood Creatine Kinase (CK) Levels up to Week 145 [ Time Frame: Baseline, up to Week 145 ]
- Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score in Ambulatory Participants up to Week 145 [ Time Frame: Baseline, up to Week 145 ]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.
- Change From Baseline in Time to Rise From Floor in Ambulatory Participants up to Week 145 [ Time Frame: Baseline, up to Week 145 ]
- Change From Baseline in 10-Meter Run/Walk (10-MRW) Time in Ambulatory Participants up to Week 145 [ Time Frame: Baseline, up to Week 145 ]
- Change From Baseline in Performance Upper Limb (PUL) Scale Version 2.0 Score up to Week 145 [ Time Frame: Baseline, up to Week 145 ]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.
- Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) up to Week 145 [ Time Frame: Baseline, up to Week 145 ]
- Change From Baseline in Stride Velocity 95th Centile (SV95C) up to Week 145 [ Time Frame: Baseline, up to Week 145 ]
- Maximum Observed Drug Concentration of DYNE-251 in Plasma (Cmax) [ Time Frame: Through study completion, up to Week 145 ]
- Time to Maximum Concentration of DYNE-251 in Plasma (tmax) [ Time Frame: Through study completion, up to Week 145 ]
- Area Under the Concentration-Time Curve From Hour 0 to the Last Measurable Concentration of DYNE-251 in Plasma (AUC0-tlast) [ Time Frame: Through study completion, up to Week 145 ]
- AUC Extrapolated to Infinity of DYNE-251 in Plasma (AUC∞) [ Time Frame: Through study completion, up to Week 145 ]
- Apparent Terminal Elimination Rate Constant of DYNE-251 in Plasma (λz) [ Time Frame: Through study completion, up to Week 145 ]
- Apparent Terminal Elimination Half-Life of DYNE-251 in Plasma (t½) [ Time Frame: Through study completion, up to Week 145 ]
- Clearance (CL) of DYNE-251 in Plasma [ Time Frame: Through study completion, up to Week 145 ]
- Volume of Distribution at the Terminal Phase of DYNE-251 in Plasma (Vz) [ Time Frame: Through study completion, up to Week 145 ]
- Volume of Distribution at Steady State of DYNE-251 in Plasma (Vss) [ Time Frame: Through study completion, up to Week 145 ]
- Tissue Phosphorodiamidate Morpholino Oligomer (PMO) Concentration of DYNE-251 in Muscle Tissue [ Time Frame: Through study completion, up to Week 145 ]
- Percentage of Participants With Antidrug Antibodies (ADAs) [ Time Frame: Through study completion, up to Week 145 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||4 Years to 16 Years (Child)|
|Sexes Eligible for Study:||Male|
|Gender Based Eligibility:||Yes|
|Accepts Healthy Volunteers:||No|
- Age 4 to 16 years inclusive, at the time of informed consent/assent.
- Male with a confirmed DMD 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 enrolment.
- 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 Period 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).
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05524883
|Contact: Dyne Clinical Trialsemail@example.com|
|United States, California|
|University of California San Diego||Recruiting|
|La Jolla, California, United States, 92037|
|Contact: Chamindra Laverty 916-799-9220 firstname.lastname@example.org|
|United States, Colorado|
|Children's Hospital Colorado||Recruiting|
|Aurora, Colorado, United States, 80045|
|Contact: Susan Apkon 720-777-8599 email@example.com, firstname.lastname@example.org|
|United States, Georgia|
|Rare Disease Research, LLC||Recruiting|
|Atlanta, Georgia, United States, 30329|
|Contact: Han Phan 678-883-6897 email@example.com|
|United States, Massachusetts|
|UMass Memorial Medical Center||Recruiting|
|Worcester, Massachusetts, United States, 01655|
|Contact: Brenda Wong 774-455-4761 firstname.lastname@example.org|
|United States, Ohio|
|Nationwide Children's Hospital||Recruiting|
|Columbus, Ohio, United States, 43205|
|Contact: Kevin Flanigan 614-722-2558 email@example.com|
|United States, Oregon|
|Shriners Hospitals for Children Portland||Recruiting|
|Portland, Oregon, United States, 97239|
|Contact: Erika Finanger, MD 503-418-8297 firstname.lastname@example.org|
|Principal Investigator: Erika Finanger, MD|
|United States, Utah|
|University of Utah - PPDS||Recruiting|
|Salt Lake City, Utah, United States, 08412|
|Contact: Russell Butterfield, MD, PhD 800-121-3359 ext 9 email@example.com|
|Principal Investigator: Russell Butterfield, MD, PhD|
|United States, Virginia|
|Virginia Commonwealth University||Recruiting|
|Richmond, Virginia, United States, 23219|
|Contact: Amy Harper 804-828-3862 firstname.lastname@example.org|
|Gent, Belgium, 9000|
|Contact: Nicolas Deconinck 3293321954 email@example.com|
|Leuven, Belgium, 3000|
|Contact: Liesbeth De Waele +1-781-317-1919 firstname.lastname@example.org|
|London Health Sciences Centre||Recruiting|
|London, Ontario, Canada, N6A 5W9|
|Contact: Craig Campbell, MD, MSc (519) 685-8441 email@example.com|
|Principal Investigator: Craig Campbell, MD, MSc|
|Hospital Universitario Vall d'Hebron - PPDS||Recruiting|
|Barcelona, Spain, 8025|
|Contact: Francina Munell 34635381625 firstname.lastname@example.org|
|Hospital Sant Joan de Déu Universidad de Barcelona||Recruiting|
|Barcelona, Spain, 8950|
|Contact: Andres Nascimento 34673135168 email@example.com|
|Royal Victoria Infirmary||Recruiting|
|Newcastle Upon Tyne, Northumberland, United Kingdom, NE1 4LP|
|Contact: Michela Guglieri, MD 441912418652 Dana.Gergely@newcastle.ac.uk|
|Principal Investigator: Michela Guglieri, MD|
|Responsible Party:||Dyne Therapeutics|
|Other Study ID Numbers:||
2021-005478-24 ( EudraCT Number )
|First Posted:||September 1, 2022 Key Record Dates|
|Last Update Posted:||May 6, 2023|
|Last Verified:||May 2023|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||No|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked