AOC 1001 for Myotonic Dystrophy

(MARINA-OLE Trial)

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

37 Participants Needed

Trial Summary

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.

How is the drug AOC 1001 unique for treating myotonic dystrophy type 1?

AOC 1001 is a novel nucleic acid-based therapy, which is different from traditional treatments as it targets the genetic cause of myotonic dystrophy type 1 by potentially correcting the mis-splicing of genes involved in the disease. This approach is part of a new wave of therapies aiming to address the underlying genetic issues rather than just managing symptoms. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is testing a new medicine called AOC 1001 to see if it is safe and effective for adults with a muscle disease called Myotonic Dystrophy Type 1. The medicine is given through an IV, and researchers want to know if it helps muscles work better.

Research Team

Li Tai, MD

Principal Investigator

Avidity Biosciences, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Genetic determinants of disease severity in the myotonic dystrophy type 1 OPTIMISTIC cohort. [2020]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Characteristics of myotonic dystrophy patients in the national registry of Japan. [2022]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

HTS-Compatible Patient-Derived Cell-Based Assay to Identify Small Molecule Modulators of Aberrant Splicing in Myotonic Dystrophy Type 1. [2021]

4. England pubmed.ncbi.nlm.nih.gov

The myotonic dystrophy type 1 drug development pipeline: 2022 edition. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Variability of multisystemic features in myotonic dystrophy type 1--lessons from Serbian registry. [2022]