AOC 1001 for Myotonic Dystrophy

(MARINA-OLE Trial)

No longer recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Avidity Biosciences, Inc.

Disqualifiers: Pregnancy, Breastfeeding, New conditions, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 58 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and effectiveness of AOC 1001 for treating adults with Myotonic Dystrophy Type 1 (DM1), a condition that causes muscle weakness and stiffness. Researchers aim to determine if regular doses of AOC 1001, administered through an IV (intravenous infusion), can better manage symptoms. Participants will receive AOC 1001 every 8 weeks, with some receiving an extra dose or a placebo on Day 43, depending on their treatment in a previous study. Individuals who completed the initial study phase without serious issues are well-suited for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that AOC 1001 is likely to be safe for humans?

Research has shown that AOC 1001 is generally safe for people with myotonic dystrophy type 1 (DM1). In earlier studies, patients taking AOC 1001 experienced no major safety issues, and most side effects, if any, were mild. Long-term results also confirmed that AOC 1001 remains safe and easy to tolerate over time. This treatment aims to improve functions like hand grip and muscle strength. Overall, the evidence suggests AOC 1001 is safe for treating DM1 in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myotonic dystrophy?

Researchers are excited about AOC 1001 for myotonic dystrophy because it introduces a novel approach compared to the current standard treatments, which primarily focus on managing symptoms rather than addressing the underlying cause. Unlike typical treatments, AOC 1001 is designed to specifically target the genetic defect responsible for myotonic dystrophy, potentially offering a more effective solution by addressing the root of the problem. This treatment is administered through a delivery method that involves quarterly doses, with the potential for more frequent dosing every eight weeks, which might improve patient outcomes and provide more consistent relief from symptoms.

What evidence suggests that AOC 1001 might be an effective treatment for Myotonic Dystrophy?

Research shows that AOC 1001, the investigational treatment in this trial, may help treat myotonic dystrophy type 1 (DM1). An earlier study found that patients experienced a slowdown in the disease's progression, particularly improving their ability to open their hands, indicating better muscle function. This is crucial because DM1 worsens over time and currently lacks approved treatments. The treatment employs a special method called Antibody Oligonucleotide Conjugates to target the disease more effectively. Overall, the early results are promising, suggesting AOC 1001 could potentially benefit those with DM1. ^{4 6 7 8 9}

Who Is on the Research Team?

Li Tai, MD

Principal Investigator

Avidity Biosciences, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with Myotonic Dystrophy Type 1 who completed the MARINA study without major issues. They must be able to continue using contraception and not be pregnant or breastfeeding. Those with new or worsening conditions that could affect their participation are excluded.

Inclusion Criteria

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

Exclusion Criteria

Unwilling or unable to continue to comply with contraceptive requirements

Pregnancy, intent to become pregnant, or active breastfeeding

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AOC 1001 administered intravenously every 8 weeks, with an additional dose on Day 43

58 months

Quarterly visits initially, then every 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

Open-label extension

Participants may continue active treatment beyond 58 months if extended by the sponsor

What Are the Treatments Tested in This Trial?

Interventions

• AOC 1001

Trial Overview The trial is an extension of a previous study, testing multiple doses of AOC 1001 administered intravenously against a placebo to assess its safety, tolerability, effectiveness, and how it's processed by the body in DM1 patients.

How Is the Trial Designed?

Group I: AOC 1001 (with Placebo at Day 43) Experimental Treatment 2 Interventions

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.

Group II: AOC 1001 Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Avidity Biosciences, Inc.

Lead Sponsor

Trials

8

Recruited

960+

Published Research Related to This Trial

There is a growing pipeline of nearly 20 candidate drugs for myotonic dystrophy type 1 (DM1), with three first-in-human clinical trials currently underway, including nucleic acid therapies AOC 1001 and DYNE-101, and the small molecule pitolisant.

Promising preclinical data for additional nucleic-acid therapies and a CRISPR-based approach suggest an increasing likelihood of successful treatments for DM1, alongside repurposed drugs like tideglusib and metformin already in clinical evaluation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The myotonic dystrophy type 1 drug development pipeline: 2022 edition. Pascual-Gilabert, M., Artero, R., López-Castel, A.[2023]

A nationwide registry for myotonic dystrophies (DM) in Japan has successfully enrolled 976 patients, primarily with DM1, providing a crucial resource for future clinical trials and therapeutic development.

The study found that longer CTG repeat lengths in DM1 patients are associated with earlier disease onset and significantly influence clinical outcomes like grip strength and lung function, highlighting the importance of genetic factors in disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics of myotonic dystrophy patients in the national registry of Japan. Sugimoto, M., Kuru, S., Takada, H., et al.[2022]

Citations

1. myotonic.org myotonic.org/sites/default/files/2024-03/3.4.24_Avidity-Letter-to-DM1-Community.pdf

March 4, 2024 AOC 1001 showed reversal of disease progression in people living with DM1 across multiple endpoints including video hand opening time (vHOT), ...

2. aviditybiosciences.com aviditybiosciences.com/pipeline/dm1

Pipeline DM1 Myotonic dystrophy type 1 (DM1) is an underrecognized, progressive and often fatal neuromuscular disease with no approved therapies.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05479981?term=NCT05479981&viewType=Table&rank=1

Extension of AOC 1001-CS1 (MARINA) Study in Adult ... Study Overview. This study will continue to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of AOC 1001 in participants ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S096089662300216X

VP55 Topline data analysis of the phase 1/2 clinical trial ... The primary objective of this study is to evaluate the safety and tolerability of single and multiple ascending doses of AOC 1001 in adults with myotonic ...

5. neurologylive.com neurologylive.com/view/fda-grants-breakthrough-therapy-designation-aoc-1001-dm1

FDA Grants Breakthrough Therapy Designation for AOC ... AOC 1001, utilizing the company's Antibody Oligonucleotide Conjugates platform, shows promise as a targeted therapy for myotonic dystrophy type ...

6. aviditybiosciences.com aviditybiosciences.com/sites/default/files/2025-04/WMS-2023-MARINA-Safety-Oral-Presentation_V9_FINAL.pdf

WMS 2023 MARINA Data Encore A Phase 1/2 Clinical Trial Evaluating the Safety and Pharmacokinetics of AOC 1001 in Adults with Myotonic Dystrophy Type 1 (DM1): MARINA™ Study Design.

7. prnewswire.com prnewswire.com/news-releases/avidity-biosciences-announces-new-positive-aoc-1001-data-demonstrating-improvement-in-multiple-additional-functional-endpoints-and-favorable-long-term-safety-and-tolerability-in-people-with-myotonic-dystrophy-type-1-301949933.html

Avidity Biosciences Announces New Positive AOC 1001 ... New AOC 1001 data demonstrate improvement in additional functional measures including hand grip, muscle strength and patient reported outcomes.

8. mdaconference.org mdaconference.org/abstract-library/a-phase-1-2-clinical-trial-evaluating-the-safety-and-pharmacokinetics-of-aoc-1001-in-adults-with-myotonic-dystrophy-type-1-dm1-marina-study-design/

A Phase 1/2 Clinical Trial Evaluating the Safety and ... The primary objective of the MARINA study is to evaluate the safety and tolerability of single and multiple ascending doses of AOC 1001 in adults with DM1.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT05479981

Extension of AOC 1001-CS1 (MARINA) Study in Adult ... 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 ...