Phase 3 Study of Delpacibart Zotadirsen in Duchenne Muscular Dystrophy with Mutations Amenable to Exon 44 Skipping

The primary objective is to evaluate the efficacy of delpacibart zotadirsen on muscle function in Duchenne muscular dystrophy, which is clinically relevant for determining whether treatment can improve or preserve functional performance in this disease. The secondary objectives are to evaluate efficacy on a biomarker of muscle injury and measures of muscle function, to assess circulating biomarkers, cardiovascular measures, patient-reported outcomes, and functional measures over time, and to characterize the safety and tolerability profile of delpacibart zotadirsen.

The trial enrolled 28 participants with Duchenne muscular dystrophy. The study population consisted of ambulatory males aged 7 to 16 years, with a documented clinical diagnosis of DMD or clear symptom onset at or before 6 years of age. Participants were selected on the basis of an acceptable genetic test confirming an out-of-frame dystrophin gene mutation amenable to exon 44 skipping. All participants were required to be on a stable corticosteroid regimen for at least 6 months before Day 1, with the regimen expected to remain stable throughout the study. Written informed consent and, where applicable, assent were obtained.

A Phase 3, randomized, double-blind, placebo-controlled study evaluates the efficacy and safety of intravenous delpacibart zotadirsen in ambulatory males with Duchenne muscular dystrophy and gene mutations amenable to exon 44 skipping. Participants are assigned to receive either the investigational product or placebo, and the main objective is to assess change in muscle function from baseline to Week 54. The trial is planned from 26 May 2026 to 31 October 2029. Study participation includes a screening visit to assess eligibility, informed consent and/or assent, genetic confirmation, age criteria, ambulatory status, and stable corticosteroid use. Eligible participants then enter the treatment period and undergo scheduled follow-up visits for efficacy and safety assessments, including functional measures, laboratory tests, vital signs, and electrocardiograms. An end-of-study visit is performed at the end of the treatment period to complete final assessments. Expected participant involvement extends through the study period up to Week 54, with continued procedures as scheduled through the end-of-study visit. Early termination may occur if eligibility is not maintained, if study requirements are not met, or if discontinuation is required for safety or other protocol-defined reasons.

The investigational treatment was AOC 1044, identified as delpacibart zotadirsen, supplied as a solution for infusion and administered by intravenous route at a dose of 5 mg/kg. The study was conducted as a randomized, double-blind, placebo-controlled trial, and the treatment assignment included an open-label extension. Administration followed the protocol-specified dosing schedule, and participant compliance was monitored according to study procedures.

The non-experimental treatment was Sodium Chloride 0.9% w/v, used as placebo. It was administered in the study under the same blinded framework as the investigational product. No additional details on formulation, dose, route, or frequency were provided in the source data.

Efficacy will be assessed by change from baseline to Week 54 in TTR velocity. Additional efficacy assessments will include change from baseline at Week 54 as per protocol and change from baseline at all visits except Week 54 in creatine kinase, 4 stair climb velocity, 10mWRT velocity, SV95C, TTR velocity, NSAA, DMD-QoL, Patient/Caregiver Global Impression of Severity, and QMT. Patient/Caregiver Global Impression of Change will also be assessed at all visits except Week 54.