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

Phase 2

Active, not recruiting

• 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.

The total duration of active treatment in AOC 1001-CS2 is up to 58 months. Once participants have completed active treatment, they will be followed through an 8-week safety follow-up period. The sponsor may extend active treatment beyond 58 months at a future timepoint.

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
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-10
• Last Update Posted: 2024-10-14
• Primary Completion: 2027-06
• Study Completion: 2027-06

Recruitment & Eligibility

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

Inclusion Criteria

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

Key

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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

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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, up to Week 248

Secondary Outcome Measures

Name	Time	Method
AOC 1001 levels in muscle tissue	Through Day 183
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	Through study completion, up to Week 248	Maximum and trough plasma concentration

Trial Locations

Locations (8)

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

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

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

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

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

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

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

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