Congenital, Hereditary, and Neonatal Diseases and Abnormalities, DMD, Duchenne Muscular Dystrophy (DMD), Genetic Disease, Inborn, Genetic Disease, X-Linked, Muscular Dystrophies, Muscular Dystrophies (Duchenne, Becker, Myotonic Dystrophy), Muscular Dystrophy (DMD), Muscular Dystrophy, Duchenne, Muscular Dystrophy, Duchenne and Becker Types, Muscular Dystrophy, Duchenne Type, Muscular Dystrophy in Children, Neuromuscular Diseases (NMD)
Conditions
Keywords
Ambulatory, DMD, Duchenne Muscular Dystrophy, Duchenne, Dyne, Dyne Therapeutics, DYNE-251, Dystrophy, Exon Skipping, Exon 51, FORZETTO, Pediatric, PMO, Muscle Function, Muscular Dystropy, Duchenne, Rise From Floor, RFF, RFF Velocity, Rostudirsen, Time to rise, TTR, TTR Velocity, Zeleciment rostudirsen, Z-rostudirsen
Brief summary
The purpose of the study is to assess the efficacy, safety, and tolerability of zeleciment rostudirsen (DYNE-251) administered intravenously (IV) every 4 weeks to ambulatory Duchenne muscular dystrophy (DMD) participants, 4 to 18 years of age, with dystrophin mutations amenable to exon 51 skipping.
Detailed description
The study consists of three periods: a Screening period (up to 6 weeks), a Placebo-Controlled Period (72 weeks) and an open-label Long-Term Extension Period (96 weeks).
Interventions
DRUGZeleciment Rostudirsen (DYNE-251)
Administered by IV infusion
DRUGPlacebo
Administered by IV infusion
Sponsors
Dyne Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
4 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Ambulatory male with confirmed diagnosis of DMD and with a mutation in the dystrophin gene characterized by exon deletion amenable to exon 51 skipping . * Rise From Floor (RFF) time must be \< 10 seconds for both screening assessments . * Receiving a stable daily or weekend dosage of glucocorticoids for at least 24 weeks prior to randomization with the expectation of maintaining a stable dose during the Placebo-Controlled Period of the study (unless dose adjustment is required by weight change)
Exclusion criteria
* Receipt of ongoing immunosuppressive therapy (other than glucocorticoids) within 12 weeks prior to randomization * Use of any pharmacologic treatment (other than glucocorticoids) that may have an effect on muscle strength or function within 12 weeks prior to randomization * Any change in prophylaxis/treatment for congestive heart failure (CHF) within 12 weeks prior to randomization * Receipt of eteplirsen within 1 week prior to randomization * Receipt of alternative exon-skipping or dystrophin-modifying therapy or zeleciment rostudirsen within 24 weeks prior to randomization * Receipt of givinostat within 12 weeks prior to randomization * Receipt of gene therapy at any time Note: Other inclusion or
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Rise From Floor (RFF) velocity | Baseline, Week 73 |
Secondary
| Measure | Time frame |
|---|---|
| RFF (Rise From Floor) velocity | Baseline, up to Week 169 |
| Stride Velocity 95th Percentile (SV95C) | Baseline, Week 73, up to Week 169 |
| North Star Ambulatory Assessment (NSAA) Total Score | Baseline, Week 73, up to Week 169 |
| 10-Meter Walk/Run (10MWR) Velocity | Baseline, Week 73, up to Week 169 |
| 4-Stair Climb (4SC) velocity | Baseline, Week 73, up to Week 169 |
| Functional Composite score | Baseline, Week 73, up to Week 169 |
| Forced Vital Capacity (FVC) | Baseline, Week 73, up to Week 169 |
| Patient Global Impression of Severity (PGI-S) | Baseline, Week 73, up to Week 169 |
| Outcome of Patient Global Impression of Change (PGI-C) | Week 73, up to Week 169 |
| Blood Creatine Kinase (CK) levels | Baseline, Week 73, up to Week 169 |
| Incidence of participants With Treatment-Emergent Adverse Events (TEAEs) | Through study completion, up to Week 173 |
| Maximum Observed Plasma Drug Concentration of DYNE-251 (Cmax) | Through study completion, up to Week 169 |
| Time to Maximum Observed Plasma Drug Concentration of DYNE-251 (tmax) | Through study completion, up to Week 169 |
| Area Under the Plasma Drug Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration of DYNE-251 in Plasma (AUC-tlast) | Through study completion, up to Week 169 |
| Area Under the Plasma Drug Concentration Versus Time Curve From Time 0 (Dosing) Extrapolated to Time Infinity of DYNE-251 (AUC∞) | Through study completion, up to Week 169 |
| Apparent Terminal Phase Elimination Rate Constant of DYNE-251 in Plasma (λz) | Through study completion, up to Week 169 |
| Apparent Terminal Elimination Half-Life of DYNE-251 in Plasma (t½) | Through study completion, up to Week 169 |
| Total Body Clearance (CL) of DYNE-251 | Through study completion, up to Week 169 |
| Volume of Distribution at the Terminal Phase of DYNE-251 in Plasma (Vz) | Through study completion, up to Week 169 |
| Volume of Distribution at Steady State of DYNE-251 in Plasma (Vss) | Through study completion, up to Week 169 |
| Incidence of Participants With Antidrug Antibodies (ADAs) | Through study completion, up to Week 169 |
Countries
United States
Contacts
CONTACTDyne Clinical Trials
Outcome results
None listed