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

Duchenne Muscular Dystrophy Clinical Trial

— EXPLORE44  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05670730
• Other study ID #: AOC 1044-CS1
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: November 9, 2022
• Est. completion date: March 2025

Study information

• Verified date: April 2024
• Source: Avidity Biosciences, Inc.
• Contact: Avidity Biosciences, Inc.
• Phone: 858-771-7038
• Email: medinfo[@]aviditybio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 64
• Est. completion date: March 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 7 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• AOC 1044
AOC 1044 will be administered via intravenous (IV) infusion
• Placebo
Placebo will be administered via intravenous (IV) infusion.

Locations

Country	Name	City	State
United States	Rare Disease Research - Atlanta	Atlanta	Georgia
United States	Abigail Research Institute at Nationwide Children's Hospital	Columbus	Ohio
United States	Rare Disease Research NC	Hillsborough	North Carolina
United States	University of Iowa	Iowa City	Iowa
United States	UCSD	La Jolla	California
United States	Arkansas Children's	Little Rock	Arkansas
United States	Stanford University	Palo Alto	California
United States	Gillette Children's	Saint Paul	Minnesota
United States	Worldwide Clinical Trials (Part A only)	San Antonio	Texas
United States	University of Massachusetts Chan Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Avidity Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-emergent adverse events (TEAEs)		Through study completion, up to Day 85 (Part A) or Day 169 (Part B)
Secondary	Plasma pharmacokinetic (PK) parameters	Maximum plasma concentration (Cmax) of AOC 1044	Through Week 8 (Part A); Through Week 12 (Part B)
Secondary	Plasma pharmacokinetic (PK) parameters	Terminal half-life (T1/2) of AOC 1044	Through Week 8 (Part A); Through Week 12 (Part B)
Secondary	Plasma pharmacokinetic (PK) parameters	Area under the concentration-time curve (AUC) of AOC 1044	Through Week 8 (Part A); Through Week 12 (Part B)
Secondary	PMO44 levels in skeletal muscle tissue		Through Week 4 (Part A); Through Week 16 (Part B)
Secondary	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)
Secondary	Change from baseline in exon skipping as measured in skeletal muscle (Part B only)		Baseline, Week 16
Secondary	Absolute change from baseline in dystrophin protein level in skeletal muscle (Part B only)		Baseline, Week 16
Secondary	Percentage change from baseline in dystrophin protein level in skeletal muscle (Part B only)		Baseline, Week 16