Duchenne Muscular Dystrophy, Exon 44
Conditions
Keywords
EXPLORE44, Avidity Biosciences, Avidity, AOC 1044
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.
Interventions
DRUGAOC 1044
AOC 1044 will be administered via intravenous (IV) infusion
DRUGPlacebo
Placebo will be administered via intravenous (IV) infusion.
Sponsors
Avidity Biosciences, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
AOC 1044-CS1 (EXPLORE44) is a 2-part study: Part A: 5 cohorts with single ascending doses conducted in healthy adult volunteers Part B: 3 cohorts with multiple ascending doses in participants with DMD mutations amenable to exon 44 skipping
Eligibility
Sex/Gender
MALE
Age
7 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | Through study completion, up to Day 85 (Part A) or Day 169 (Part B) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PMO44 levels in skeletal muscle tissue | Through Week 4 (Part A); Through Week 16 (Part B) | — |
| 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) | Maximum plasma concentration (Cmax) of AOC 1044 |
| Absolute change from baseline in dystrophin protein level 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 | — |
| Change from baseline in exon skipping as measured in skeletal muscle (Part B only) | Baseline, Week 16 | — |
Countries
United States
Outcome results
None listed