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

Phase 1

Recruiting

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

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

Arm && Interventions

Group	Intervention	Description
AOC 1044-CS1 Part B - Multiple Ascending Dose: Placebo	Placebo	Placebo will be administered three times.
AOC 1044-CS1 Part A - Single Dose Levels 1-5	AOC 1044	AOC 1044 will be administered once.
AOC 1044-CS1 Part A - Single Dose: Placebo	Placebo	Placebo will be administered once.
AOC 1044-CS1 Part B - Multiple Ascending Dose Levels 1-3	AOC 1044	AOC 1044 will be administered three times.

Primary Outcome Measures

Name	Time	Method
Incidence of treatment-emergent adverse events (TEAEs)	Through study completion, up to Day 85 (Part A) or Day 169 (Part B)

Secondary Outcome Measures

Name	Time	Method
Change from baseline in exon skipping as measured in skeletal muscle (Part B only)	Baseline, Week 16
Percentage change from baseline in dystrophin protein level in skeletal muscle (Part B only)	Baseline, Week 16
Urine pharmacokinetic parameters	Day 1-2 (0-24 hours after first dose) (Part A); Day 1-2 (0-24 hours after first dose) (Part B)	Fraction of PMO44 excreted in urine
Plasma pharmacokinetic (PK) parameters	Through Week 8 (Part A); Through Week 12 (Part B)	Area under the concentration-time curve (AUC) of AOC 1044
PMO44 levels in skeletal muscle tissue	Through Week 4 (Part A); Through Week 16 (Part B)
Absolute change from baseline in dystrophin protein level in skeletal muscle (Part B only)	Baseline, Week 16

Locations (10): Arkansas Children's
🇺🇸
Little Rock, Arkansas, United States
UCSD
🇺🇸
La Jolla, California, United States
Stanford University
🇺🇸
Palo Alto, California, United States
Rare Disease Research - Atlanta
🇺🇸
Atlanta, Georgia, United States
University of Iowa
🇺🇸
Iowa City, Iowa, United States
University of Massachusetts Chan Medical School
🇺🇸
Worcester, Massachusetts, United States
Gillette Children's
🇺🇸
St. Paul, Minnesota, United States
Rare Disease Research NC
🇺🇸
Hillsborough, North Carolina, United States
Abigail Research Institute at Nationwide Children's Hospital
🇺🇸
Columbus, Ohio, United States
Worldwide Clinical Trials (Part A only)
🇺🇸
San Antonio, Texas, United States