Study of AOC 1044 in Healthy Adult Volunteers and Participants With Duchenne Muscular Dystrophy (DMD) Mutations Amenable to Exon 44 Skipping

AOC 1044-CS1 (EXPLORE44) is a Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending doses of AOC 1044 in healthy adult volunteers and participants with DMD mutations amenable to exon 44 skipping.Part A is a single dose design with multiple cohorts (dose levels) in healthy adult volunteers.Part B is a multiple-ascending dose design with 3 cohorts (dose levels) in participants with Duchenne.

Part A:Key Inclusion Criteria:Aged 18 to 45 years, inclusive, at the time of informed consentBody mass index (BMI) of 18.5 to 32.0 kg/m2Key Exclusion Criteria:Clinically significant abnormalities in laboratory results, ECGs, or vitalsCurrent or recent use of prescription or nonprescription drugsPositive drug/alcohol test at Screening or Day -1Elevated blood pressure (BP) >130/80 mmHg at ScreeningParticipation in a clinical study in which an investigational product was received within 1 month of screening or 5 half-lives of the investigational productBlood or plasma donation within 16 weeks of planned AOC 1044 administration Note: Other protocol defined Inclusion/Exclusion criteria may applyPart B:Key Inclusion Criteria:Aged 7 to 27 years, inclusive, at the time of informed consentClinical diagnosis of DMD or clear onset of DMD symptoms at or before the age of 6 yearsConfirmation of DMD gene mutation amenable to exon 44 skippingWeight ≥ 30.5 kgAmbulatory or non-ambulatoryAmbulatory participants: LVEF ≥50% and FVC≥50%Non-ambulatory participants: LVEF ≥45% and FVC≥40%PUL 2.0 entry item A ≥3If on corticosteroids, stable dose for 30 days before screening and throughout the study Key Exclusion CriteriaBiceps brachii muscles unsuitable for biopsySerum hemoglobin < lower limit of normalUncontrolled hypertension or diabetesPrior treatment with any cell or gene therapyPrior treatment with another exon 44 skipping agent within 6 months prior to informed consentRecently treated with an investigational drugHistory of multiple drug allergies