Congenital, DMD, Duchene Muscular Dystrophy, Genetic Diseases, Hereditary, Muscular Disease, Muscular Disorders, Atrophic, Muscular Dystrophies, Muscular Dystrophies (Duchenne, Becker, Myotonic Dystrophy), Musculoskeletal Diseases, Neonatal Disease, Nervous System Diseases, Neuromuscular Diseases (NMD), X-Linked
Conditions
Keywords
AOC, AOC 1044, AOC 1044-CS3, AOC 1044-CS1, AOC 1044-CS2, EXPLORE44, EXPLORE44-OLE, SAFARI, SAFARI44, SAFARI 44, Avidity, Avidity Biosciences, Exon Skipping Therapy, Avidity Biosciences Inc., A Novartis Company, del-zota, DMD
Brief summary
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
Detailed 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.
Interventions
DRUGAOC 1044
AOC 1044 will be administered by intravenous (IV) infusion
DRUGPlacebo
Placebo will be administered by intravenous (IV) infusion
Sponsors
Avidity Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
7 Years to 16 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from Baseline in Time to Rise (TTR) Velocity at Week 54 | Baseline, Week 54 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Creatine Kinase (CK) at Week 54 | Baseline, Week 54 | — |
| Change from Baseline in 4-Stair Climb (4SC) Velocity at Week 54 | Baseline, Week 54 | — |
| Change from Baseline in 10-Meter Walk/Run Test (10MWRT) Velocity at Week 54 | Baseline, Week 54 | — |
| Change from Baseline in Stride Velocity 95th Centile (SV95C) at Week 54 | Baseline, Week 54 | — |
| Change from Baseline in North Star Ambulatory Assessment (NSAA) Total Score at Week 54 | Baseline, Week 54 | — |
| Change from Baseline in DMD Quality of Life (DMD-QoL) Score at Week 54 | Baseline, Week 54 | — |
| Change from Baseline in Patient Global Impression of Severity (PGI-S) at Week 54 | Baseline, Week 54 | — |
| Change from Baseline in Caregiver Global Impression of Severity (CaGI-S) at Week 54 | Baseline, Week 54 | — |
| Patient Global Impression of Change (PGI-C) at Week 54 | Week 54 | — |
| Caregiver Global Impression of Change (CaGI-C) at Week 54 | Week 54 | Caregiver Global Impression of Change (CaGI-C) at Week 54 |
| Change from Baseline in Quantitative Muscle Testing (QMT) at Week 54 | Baseline, Week 54 | — |
Countries
Belgium, France, Germany, Italy, Spain, United Kingdom
Contacts
CONTACTAvidity Bioscience, Inc., A Novartis Company
Outcome results
None listed