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

A Phase 1/2, Randomized, Placebo-controlled, Double-blind, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Single and Multiple Ascending Doses of AOC 1044 Administered Intravenously to Healthy Adult Volunteers and Participants With 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 55 years, inclusive, at the time of informed consent
• Body mass index (BMI) of 18.5 to 32.0 kg/m2

Key Exclusion Criteria:

• Clinically significant abnormalities in laboratory results, ECGs, or vitals
• Current or recent use of prescription or nonprescription drugs
• Positive drug/alcohol test at Screening or Day -1
• Elevated blood pressure (BP) >130/80 mmHg at Screening
• Participation in a clinical study in which an investigational product was received within 1 month of screening or 5 half-lives of the investigational product
• Blood or plasma donation within 16 weeks of planned AOC 1044 administration Note: Other protocol defined Inclusion/Exclusion criteria may apply

Part B:

Key Inclusion Criteria:

• Aged 7 to 27 years, inclusive, at the time of informed consent

• Clinical diagnosis of DMD or clear onset of DMD symptoms at or before the age of 6 years

• Confirmation of DMD gene mutation amenable to exon 44 skipping

• Weight ≥ 23 kg

• Ambulatory or non-ambulatory

  • Ambulatory participants: LVEF ≥50% and FVC≥50%
  • Non-ambulatory participants: LVEF ≥45% and FVC≥40%

• PUL 2.0 entry item A ≥3

• If on corticosteroids, stable dose for 30 days before screening and throughout the study

Key Exclusion Criteria:

• Biceps brachii muscles unsuitable for biopsy
• Serum hemoglobin < lower limit of normal
• Uncontrolled hypertension or diabetes
• Prior treatment with any cell or gene therapy
• Prior treatment with another exon 44 skipping agent within 6 months prior to informed consent
• Recently treated with an investigational drug
• History of multiple drug allergies