Extension of AOC 1001-CS1 (MARINA) Study in Adult Myotonic Dystrophy Type 1 (DM1) Patients

Phase 2

Completed

• Conditions: Musculoskeletal Diseases; DM1; Myotonic Dystrophy; Muscular Disorders, Atrophic; Muscular Dystrophies; Myotonic Disorders; Genetic Diseases, Inborn; Muscular Diseases; Myotonic Dystrophy 1; Neuromuscular Diseases
• Interventions: Drug: AOC 1001; Drug: Placebo

• Registration Number: NCT05479981
• Lead Sponsor: Avidity Biosciences, Inc.

Brief Summary

AOC 1001-CS2 (MARINA-OLE) is a Phase 2 extension of the AOC 1001-CS1 (MARINA) study to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of multiple-doses of AOC 1001 Administered Intravenously to Adult Myotonic Dystrophy Type 1 (DM1) patients

Detailed Description

This study will continue to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AOC 1001 in participants that enrolled in the randomized, placebo-controlled, First-In-Human Phase 1/2 AOC 1001-CS1 (MARINA) clinical study.

Participants from AOC 1001-CS1 are eligible to enroll in AOC 1001-CS2 if they have satisfactorily completed AOC 1001-CS1.

After completion of Q8W Visit 6 assessments, participants will have the option to enroll in another AOC 1001 open-label extension (OLE) study. Participants who do not enroll in an AOC 1001 OLE study will be monitored for safety for a total of 8 weeks from the last dose of study drug. Total duration on study is up to 37 months (3 years 1 month).

As of September 2024, the dosing regimen was updated to every 8 weeks.

Study Timeline

• Study First Submitted: 2022-07-27
• Study First Submitted QC: 2022-07-27
• Study First Posted: 2022-07-29
• Study Start: 2022-08-04
• Primary Completion: 2025-09-05
• Study Completion: 2025-09-10
• Status Verified: 2025-10
• Last Update Submitted: 2025-10-06
• Last Update Posted: 2025-10-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 37

Inclusion Criteria

• Completion of AOC 1001-CS1 (MARINA) study with satisfactory compliance and no significant tolerability issues

Key

Exclusion Criteria

• Pregnancy, intent to become pregnant, or active breastfeeding
• Unwilling or unable to continue to comply with contraceptive requirements
• Any new conditions or worsening of existing conditions that in the opinion of the investigator or sponsor would make the participant unsuitable for the study or could interfere with participation or completion of the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AOC 1001	AOC 1001	AOC 1001 will initially be administered quarterly. On Day 43 patients will receive an additional dose. Treatment assignment will be based on treatment received in AOC 1001-CS1. If participant did not receive AOC 1001 on Day 43 in AOC 1001-CS1, participant will receive AOC 1001 treatment on Day 43 in AOC 1001-CS2. Beginning in September 2024, AOC 1001 will be administered every 8 weeks.
AOC 1001 (with Placebo at Day 43)	Placebo	AOC 1001 will initially be administered quarterly. On Day 43 patients will receive an additional dose. Treatment assignment will be based on treatment received in AOC 1001-CS1. If participant received AOC 1001 on Day 43 in AOC 1001-CS1, participant will receive blinded placebo treatment on Day 43 in AOC 1001-CS2. Beginning in September 2024, AOC 1001 will be administered every 8 weeks.
AOC 1001 (with Placebo at Day 43)	AOC 1001	AOC 1001 will initially be administered quarterly. On Day 43 patients will receive an additional dose. Treatment assignment will be based on treatment received in AOC 1001-CS1. If participant received AOC 1001 on Day 43 in AOC 1001-CS1, participant will receive blinded placebo treatment on Day 43 in AOC 1001-CS2. Beginning in September 2024, AOC 1001 will be administered every 8 weeks.

Primary Outcome Measures

Name	Time	Method
Number and severity of treatment-emergent adverse events (TEAEs)	Through study completion

Secondary Outcome Measures

Name	Time	Method
Change and percentage change from baseline in DMPK mRNA knockdown	Through Day 183
Change and percentage change from baseline in Spliceopathy	Through Day 183
Plasma pharmacokinetic (PK) parameters	Up to Day 729	Maximum and trough plasma concentration
AOC 1001 levels in muscle tissue	Through Day 183

Trial Locations

Locations (8)

University of California Los Angeles; 🇺🇸 Los Angeles, California, United States

Stanford University; 🇺🇸 Palo Alto, California, United States

University of Colorado; 🇺🇸 Denver, Colorado, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

Kansas University Medical Center; 🇺🇸 Kansas City, Kansas, United States

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States