Clinical trial NCT05670730: Study of AOC 1044 in Healthy Adult Volunteers and Participants with Duchenne Muscular Dystrophy (DMD) Mutations Amenable to Exon 44 Skipping
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Duchenne Muscular Dystrophy
Exon 44
Keywords: EXPLORE44
Avidity Biosciences
Avidity
AOC 1044
Lead sponsor: Avidity Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-04
Enrollment: 70
Sex: MALE
Minimum age (years): 7
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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
Primary purpose: TREATMENT

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.


Eligibility 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/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

Primary outcomes:
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Through study completion, up to Day 85 (Part A) or Day 169 (Part B)
Secondary outcomes:
measure: Plasma pharmacokinetic (PK) parameters
timeFrame: Through Week 8 (Part A); Through Week 12 (Part B)
measure: Plasma pharmacokinetic (PK) parameters
timeFrame: Through Week 8 (Part A); Through Week 12 (Part B)
measure: Plasma pharmacokinetic (PK) parameters
timeFrame: Through Week 8 (Part A); Through Week 12 (Part B)
measure: PMO44 levels in skeletal muscle tissue
timeFrame: Through Week 4 (Part A); Through Week 16 (Part B)
measure: Urine pharmacokinetic parameters
timeFrame: Day 1-2 (0-24 hours after first dose) (Part A); Day 1-2 (0-24 hours after first dose) (Part B)
measure: Change from baseline in exon skipping as measured in skeletal muscle (Part B only)
timeFrame: Baseline, Week 16
measure: Absolute change from baseline in dystrophin protein level in skeletal muscle (Part B only)
timeFrame: Baseline, Week 16
measure: Percentage change from baseline in dystrophin protein level in skeletal muscle (Part B only)
timeFrame: Baseline, Week 16
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's
state: Arkansas
city: La Jolla
country: United States
facility: UCSD
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Atlanta
country: United States
facility: Rare Disease Research - Atlanta
state: Georgia
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Worcester
country: United States
facility: University of Massachusetts Chan Medical School
state: Massachusetts
city: St. Paul
country: United States
facility: Gillette Children's
state: Minnesota
city: Hillsborough
country: United States
facility: Rare Disease Research NC
state: North Carolina
city: Columbus
country: United States
facility: Abigail Research Institute at Nationwide Children's Hospital
state: Ohio
city: San Antonio
country: United States
facility: Worldwide Clinical Trials (Part A only)
state: Texas
Study officials:
affiliation: Avidity Biosciences, Inc.
name: Carmen Castrillo, MD
role: STUDY_DIRECTOR
References: