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Trial record 1 of 1 for:    NCT05524883
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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 : October 24, 2022
Sponsor:
Information provided by (Responsible Party):
Dyne Therapeutics

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 period (96 weeks).


Condition or disease Intervention/treatment Phase
Duchenne Muscular Dystrophy (DMD) Drug: DYNE-251 Drug: Placebo Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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


Arm Intervention/treatment
Experimental: Placebo-Controlled MAD Period - DYNE-251
DYNE-251 will be administered 6 times over 24 weeks.
Drug: DYNE-251
Administered by IV infusion, every 4 weeks

Experimental: Placebo-Controlled MAD Period - Placebo
Placebo will be administered 6 times over 24 weeks.
Drug: Placebo
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.
Drug: DYNE-251
Administered by IV infusion, every 4 weeks




Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: Through study completion, up to Week 145 ]
  2. Change From Baseline in Dystrophin Protein Levels in Muscle Tissue at Week 25 [ Time Frame: Baseline, Week 25 ]

Secondary Outcome Measures :
  1. Change From Baseline in Muscle Tissue Exon 51 Skipping Levels at Week 25 [ Time Frame: Baseline, Week 25 ]
  2. Change From Baseline in Muscle Tissue Percent Dystrophin-Positive Fiber (PDPF) at Week 25 [ Time Frame: Baseline, Week 25 ]
  3. Change From Baseline in Blood Creatine Kinase (CK) Levels up to Week 145 [ Time Frame: Baseline, up to Week 145 ]
  4. 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.

  5. Change From Baseline in Time to Rise From Floor in Ambulatory Participants up to Week 145 [ Time Frame: Baseline, up to Week 145 ]
  6. 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 ]
  7. 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.

  8. Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) up to Week 145 [ Time Frame: Baseline, up to Week 145 ]
  9. Maximum Observed Drug Concentration of DYNE-251 in Plasma (Cmax) [ Time Frame: Through study completion, up to Week 145 ]
  10. Time to Maximum Concentration of DYNE-251 in Plasma (tmax) [ Time Frame: Through study completion, up to Week 145 ]
  11. 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 ]
  12. AUC Extrapolated to Infinity of DYNE-251 in Plasma (AUC∞) [ Time Frame: Through study completion, up to Week 145 ]
  13. Apparent Terminal Elimination Rate Constant of DYNE-251 in Plasma (λz) [ Time Frame: Through study completion, up to Week 145 ]
  14. Apparent Terminal Elimination Half-Life of DYNE-251 in Plasma (t½) [ Time Frame: Through study completion, up to Week 145 ]
  15. Clearance (CL) of DYNE-251 in Plasma [ Time Frame: Through study completion, up to Week 145 ]
  16. Volume of Distribution at the Terminal Phase of DYNE-251 in Plasma (Vz) [ Time Frame: Through study completion, up to Week 145 ]
  17. Volume of Distribution at Steady State of DYNE-251 in Plasma (Vss) [ Time Frame: Through study completion, up to Week 145 ]
  18. Tissue Phosphorodiamidate Morpholino Oligomer (PMO) Concentration of DYNE-251 in Muscle Tissue [ Time Frame: Through study completion, up to Week 145 ]
  19. Percentage of Participants With Antidrug Antibodies (ADAs) [ Time Frame: Through study completion, up to Week 145 ]


Information from the National Library of Medicine

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Ages Eligible for Study:   4 Years to 16 Years   (Child)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • 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.


Information from the National Library of Medicine

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


Contacts
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Contact: Dyne Clinical Trials +1-781-317-1919 clinicaltrials@dyne-tx.com

Locations
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United States, Colorado
Children's Hospital Colorado Recruiting
Aurora, Colorado, United States, 80045
Contact: Susan Apkon    303-898-2475    kyle.kusmik@childrenscolorado.org   
United States, Georgia
Rare Disease Research, LLC Recruiting
Atlanta, Georgia, United States, 30329
Contact: Han Phan    678-883-6897    marcial.almaraz@rarediseaseresearch.com   
United States, Massachusetts
UMass Memorial Medical Center Recruiting
Worcester, Massachusetts, United States, 01655
Contact: Brenda Wong    774-441-7616    hannah.alongi@umassmed.edu   
Sponsors and Collaborators
Dyne Therapeutics
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Responsible Party: Dyne Therapeutics
ClinicalTrials.gov Identifier: NCT05524883    
Other Study ID Numbers: DYNE251-DMD-201
2021-005478-24 ( EudraCT Number )
First Posted: September 1, 2022    Key Record Dates
Last Update Posted: October 24, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Muscular Dystrophies
Muscular Dystrophy, Duchenne
Muscular Disorders, Atrophic
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases
Genetic Diseases, Inborn
Genetic Diseases, X-Linked