A Phase 3 Study to Evaluate the Safety and Efficacy of AOC 1044 (Also Referred to as Delpacibart Zotadirsen) in Participants With DMD With Gene Mutations Amenable to Exon 44 Skipping (SAFARI44)

Avidity Biosciences

Status and phase: Not yet enrolling; Phase 3

Conditions: DMD; Musculoskeletal Diseases; Nervous System Diseases; X-Linked; Muscular Disease; Neonatal Disease; Hereditary; Neuromuscular Diseases (NMD); Congenital; Genetic Diseases; Muscular Dystrophies (Duchenne, Becker, Myotonic Dystrophy); Duchene Muscular Dystrophy; Muscular Disorders, Atrophic; Muscular Dystrophies

Treatments: Drug: AOC 1044; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07587242

AOC 1044-CS3

Details and patient eligibility

About

A Randomized, Double-blind, Placebo-controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Intravenous AOC 1044 for the treatment of Duchenne Muscular Dystrophy (DMD) with Gene Mutations Amenable to Exon 44 Skipping

Full description

The study consists of a Screening Period of up to 44 Days, a Randomized 54 Week Treatment Period, a 54 Week Open Label Extension (OLE), and a Follow-Up Period of 6 weeks. Participants will be randomized to receive an intravenous infusion of either delpacibart-zotadirsen or placebo at the clinical study site every 6 weeks for a total of 9 doses. After completion of the randomized treatment period, all participants may enter the OLE portion of the study consisting of 9 doses of AOC 1044 regardless of group assignment in the randomized period. The final dose will occur at Week 102, followed by a final assessment at Week 108 and a safety follow-up visit at Week 114. An Independent Data Monitoring Committee (IDMC) comprising members independent and external to the Sponsor will review safety, tolerability, and efficacy (as needed) data of this study at regular intervals.

Enrollment: 70 estimated patients

Sex: Male

Ages: 7 to 16 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Ambulatory males with clinical and genetic diagnosis of DMD
• Acceptable genetic test confirming dystrophin gene mutation amenable to exon 44 skipping
• 7 to 16 years of age at time of consent
• TTR and NSAA assessment completed within the protocol specified parameters at Screening
• On a stable regimen of corticosteroids (including Vamolorone) for at least 6 months prior to Day 1. Steroid regimen must be anticipated to remain stable.

Key Exclusion Criteria:

• Previous treatment cell or gene therapy.
• Treatment with another oligonucleotide within 6 months of informed consent (not including COVID-19 RNA vaccines).
• Lab values outside of the protocol specified range at Screening
• If on any of the following treatments (growth hormone, testosterone or givinostat), participants must be on a stable regimen and must plan to maintain it for the duration of the study. Participants will be excluded if regimen stability prior to informed consent is as follows:
• Less than 1 month, for growth hormone and/or testosterone
• Less than 6 months for givinostat

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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70 participants in 2 patient groups, including a placebo group

AOC 1044

Experimental group

Description:

Participants will receive AOC 1044 intravenously (IV) every 6 weeks (Q6W) during the 54-week double-blind treatment period, followed by a 54-week open-label treatment period in which the same participants will continue to receive AOC 1044 IV Q6W

Treatment:

Drug: AOC 1044

Placebo

Placebo Comparator group

Description:

Participants will receive placebo (saline) IV Q6W during the 54-week double-blind treatment period, followed by a 54-week open-label treatment period in which all participants will then receive AOC 1044 IV Q6W

Treatment:

Drug: Placebo