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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Exon 44, Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: AOC 1044
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Interventional 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AOC 1044-CS1 Part A - Single Dose Levels 1-5<br>AOC 1044 will be administered once. | Drug: AOC 1044<br>* AOC 1044 will be administered via intravenous (IV) infusion<br>|
| Placebo Comparator: AOC 1044-CS1 Part A - Single Dose: Placebo<br>Placebo will be administered once. | Drug: Placebo<br>* Placebo will be administered via intravenous (IV) infusion.<br>* Other names: Saline;|
| Experimental: AOC 1044-CS1 Part B - Multiple Ascending Dose Levels 1-3<br>AOC 1044 will be administered three times. | Drug: AOC 1044<br>* AOC 1044 will be administered via intravenous (IV) infusion<br>|
| Placebo Comparator: AOC 1044-CS1 Part B - Multiple Ascending Dose: Placebo<br>Placebo will be administered three times. | Drug: Placebo<br>* Placebo will be administered via intravenous (IV) infusion.<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) |  | Through study completion, up to Day 85 (Part A) or Day 169 (Part B) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma pharmacokinetic (PK) parameters | Maximum plasma concentration (Cmax) of AOC 1044 | Through Week 8 (Part A); Through Week 12 (Part B) | 
| Plasma pharmacokinetic (PK) parameters | Terminal half-life (T1/2) of AOC 1044 | Through Week 8 (Part A); Through Week 12 (Part B) | 
| Plasma pharmacokinetic (PK) parameters | Area under the concentration-time curve (AUC) of AOC 1044 | Through Week 8 (Part A); Through Week 12 (Part B) | 
| PMO44 levels in skeletal muscle tissue |  | Through Week 4 (Part A); Through Week 16 (Part B) | 
| Urine pharmacokinetic parameters | Fraction of PMO44 excreted in urine | 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) |  | Baseline, Week 16 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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EXPLORE44, Avidity Biosciences, Avidity, AOC 1044