Study of AOC 1044 in Healthy Adult Volunteers and Participants With Duchenne Muscular Dystrophy (DMD) Mutations Amenable to Exon 44 Skipping (EXPLORE44)

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

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 Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy; Exon 44
• Intervention / Treatment: Drug: AOC 1044; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Avidity Biosciences, Inc.; Phone Number: 858-771-7038; Email: medinfo@aviditybio.com

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Recruiting
      • Arkansas Children's
      • Contact: Ashley Bryan
  • California
    • La Jolla, California, United States, 92037
      • Recruiting
      • UCSD
      • Contact: Parissa Shayesteh
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford University
      • Contact: Rabia Farooquee
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Recruiting
      • Rare Disease Research - Atlanta
      • Contact: Laura Sutton
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • University of Iowa
      • Contact: Laura Knosp
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • Recruiting
      • University of Massachusetts Chan Medical School
      • Contact: Sarah Figueira
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Recruiting
      • Gillette Children's
      • Contact: Laura Feldman
  • North Carolina
    • Hillsborough, North Carolina, United States, 27278
      • Recruiting
      • Rare Disease Research NC
      • Contact: Annette Babu
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Recruiting
      • Abigail Research Institute at Nationwide Children's Hospital
      • Contact: Regina Flomo
  • Texas
    • San Antonio, Texas, United States, 78217
      • Active, not recruiting
      • Worldwide Clinical Trials (Part A only)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 55 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 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

Collaborators and Investigators

• Sponsor: Avidity Biosciences, Inc.
• Investigators: Study Director: Marc Morris, MD, JD, MS, Avidity Biosciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2022
• Primary Completion (Estimated): March 1, 2025
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: December 6, 2022
• First Submitted That Met QC Criteria: January 2, 2023
• First Posted (Actual): January 4, 2023

Study Record Updates

• Last Update Posted (Actual): April 25, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Avidity Biosciences; Avidity; EXPLORE44; AOC 1044
• Additional Relevant MeSH Terms: Nervous System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: AOC 1044-CS1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No