Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-251 in Participants With Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping (DELIVER)
|
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT05524883 |
|
Recruitment Status :
Recruiting
First Posted : September 1, 2022
Last Update Posted : March 13, 2024
|
Sponsor:
Dyne Therapeutics
Information provided by (Responsible Party):
Dyne Therapeutics
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 88 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 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Muscular Dystrophy
| 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 96 weeks after participants complete the Placebo-Controlled MAD Period of the study.
|
Drug: DYNE-251
Administered by IV infusion |
Primary Outcome Measures :
- 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 ]
Secondary Outcome Measures :
- 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 [ Time Frame: 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 [ Time Frame: Baseline, Week 25 ]
- Change From Baseline in Blood Creatine Kinase (CK) Levels up to Week 145 For Participants Dosed at Q4W or Q8W Interval With a Second Biopsy Performed at Week 25 [ Time Frame: Baseline, up to Week 145 ]
- 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline, Week 49 ]
- Change From Baseline in Blood CK Levels up to Week 145 For Participants Dosed at Q8W Interval With a Second Biopsy Performed at Week 49 [ 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 (10MRW) 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) in Ambulatory Participants up to Week 145 [ Time Frame: Baseline, up to Week 145 ]
- Maximum Observed Plasma Drug Concentration of DYNE-251 (Cmax) [ Time Frame: Through study completion, up to Week 145 ]
- Time to Maximum Observed Plasma Drug Concentration of DYNE-251 (tmax) [ Time Frame: Through study completion, up to Week 145 ]
- Area Under the Plasma Drug Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration of DYNE-251 in Plasma (AUC0-tlast) [ Time Frame: Through study completion, up to Week 145 ]
- Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 (Dosing) Extrapolated to Time Infinity of DYNE-251 (AUC∞) [ Time Frame: Through study completion, up to Week 145 ]
- Apparent Terminal Phase 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 ]
- Total Body Clearance (CL) of DYNE-251 [ 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 ]
Information from the National Library of Medicine
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 |
Criteria
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 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 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.
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
| Contact: Dyne Clinical Trials | +1-781-317-1919 | clinicaltrials@dyne-tx.com |
Locations
Show 25 study locations
Sponsors and Collaborators
Dyne Therapeutics
| 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: | March 13, 2024 |
| Last Verified: | March 2024 |
| 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 |
Additional relevant MeSH terms:
|
Muscular Dystrophies Muscular Dystrophy, Duchenne Muscular Disorders, Atrophic Muscular Diseases Musculoskeletal Diseases |
Neuromuscular Diseases Nervous System Diseases Genetic Diseases, Inborn Genetic Diseases, X-Linked |