Efficacy, Safety, and Tolerability of Zeleciment Rostudirsen (DYNE-251) Administered Intravenously Every 4 Weeks in Ambulatory Participants With Duchenne Muscular Dystrophy (FORZETTO)

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).

• Zeleciment Rostudirsen (DYNE-251) (Drug): Administered by IV infusion
• Placebo (Drug): Administered by IV infusion

Primary outcomes

• Rise From Floor (RFF) velocity [Baseline, Week 73]

Secondary outcomes

• 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]

Sex: Male, ages: 4 Years to 18 Years

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 exclusion criteria may apply

NIH grants: 2025