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

• Register: ClinicalTrials.gov
• Last refreshed on: 3 February 2025
• Main ID: NCT05524883
• Date of registration: 30/08/2022
• Prospective Registration: No
• Primary sponsor: Dyne Therapeutics
• Public title: Safety, Tolerability, Pharmacodynamic, Efficacy, and Pharmacokinetic Study of DYNE-251 in Participants with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping DELIVER
• Scientific 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
• Date of first enrolment: August 12, 2022
• Target sample size: 88
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT05524883
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 1/Phase 2

Countries of recruitment

Australia, Belgium, Canada, Ireland, Italy, Korea, Republic of, Spain, United Kingdom, United States

Contacts

• Name: Dyne Clinical Trials

Key inclusion & exclusion 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 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.


Age minimum: 4 Years
Age maximum: 16 Years
Gender: Male

Health Condition(s) or Problem(s) studied

Duchenne Muscular Dystrophy (DMD)

Intervention(s)

Drug: DYNE-251

Drug: Placebo

Primary Outcome(s)

Change From Baseline in Dystrophin Protein Levels in Muscle Tissue at Week 25 [Time Frame: Baseline, Week 25]

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Time Frame: Through study completion, up to Week 241]

Secondary Outcome(s)

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 241]

Change From Baseline in Time to Rise From Floor in Ambulatory Participants up to Week 241 [Time Frame: Baseline, up to Week 241]

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 Stride Velocity 95th Centile (SV95C) in Ambulatory Participants up to Week 241 [Time Frame: Baseline, up to Week 241]

Apparent Terminal Elimination Half-Life of DYNE-251 in Plasma (t½) [Time Frame: Through study completion, up to Week 241]

Apparent Terminal Phase Elimination Rate Constant of DYNE-251 in Plasma (?z) [Time Frame: 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 (AUC8) [Time Frame: Through study completion, up to Week 241]

Volume of Distribution at the Terminal Phase of DYNE-251 in Plasma (Vz) [Time Frame: Through study completion, up to Week 241]

Tissue Phosphorodiamidate Morpholino Oligomer (PMO) Concentration of DYNE-251 in Muscle Tissue [Time Frame: Through study completion, up to Week 241]

Volume of Distribution at Steady State of DYNE-251 in Plasma (Vss) [Time Frame: Through study completion, up to Week 241]

Change From Baseline in North Star Ambulatory Assessment (NSAA) Total Score in Ambulatory Participants up to Week 241 [Time Frame: Baseline, up to Week 241]

Maximum Observed Plasma Drug Concentration of DYNE-251 (Cmax) [Time Frame: Through study completion, up to Week 241]

Change From Baseline in 10-Meter Run/Walk (10MRW) Time in Ambulatory Participants up to Week 241 [Time Frame: 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 [Time Frame: Baseline, up to Week 241]

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 [Time Frame: Baseline, up to Week 241]

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 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 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]

Percentage of Participants With Antidrug Antibodies (ADAs) [Time Frame: Through study completion, up to Week 241]

Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) up to Week 241 [Time Frame: Baseline, up to Week 241]

Total Body Clearance (CL) of DYNE-251 [Time Frame: Through study completion, up to Week 241]

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 Performance Upper Limb (PUL) Scale Version 2.0 Score up to Week 241 [Time Frame: Baseline, up to Week 241]

Time to Maximum Observed Plasma Drug Concentration of DYNE-251 (tmax) [Time Frame: Through study completion, up to Week 241]

Secondary ID(s)

2023-510351-31-00

DYNE251-DMD-201

Source(s) of Monetary Support

Please refer to primary and secondary sponsors