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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
70
AOC 1044 will be administered via intravenous (IV) infusion
Placebo will be administered via intravenous (IV) infusion.
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
Saint 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
Incidence of treatment-emergent adverse events (TEAEs)
Time frame: Through study completion, up to Day 85 (Part A) or Day 169 (Part B)
Plasma pharmacokinetic (PK) parameters
Maximum plasma concentration (Cmax) of AOC 1044
Time frame: Through Week 8 (Part A); Through Week 12 (Part B)
Plasma pharmacokinetic (PK) parameters
Terminal half-life (T1/2) of AOC 1044
Time frame: Through Week 8 (Part A); Through Week 12 (Part B)
Plasma pharmacokinetic (PK) parameters
Area under the concentration-time curve (AUC) of AOC 1044
Time frame: Through Week 8 (Part A); Through Week 12 (Part B)
PMO44 levels in skeletal muscle tissue
Time frame: Through Week 4 (Part A); Through Week 16 (Part B)
Urine pharmacokinetic parameters
Fraction of PMO44 excreted in urine
Time frame: Day 1-2 (0-24 hours after first dose) (Part A); Day 1-2 (0-24 hours after first dose) (Part B)
Change from baseline in exon skipping as measured in skeletal muscle (Part B only)
Time frame: Baseline, Week 16
Absolute change from baseline in dystrophin protein level in skeletal muscle (Part B only)
Time frame: Baseline, Week 16
Percentage change from baseline in dystrophin protein level in skeletal muscle (Part B only)
Time frame: Baseline, Week 16
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