What is the mechanism of action of this treatment?

Common treatments for muscular disorders, such as RNA modulation and gene therapy, work by targeting the genetic and molecular basis of these conditions. RNA modulation, including antisense oligonucleotides like Tofersen, aims to correct or modify the expression of defective genes by binding to specific RNA sequences, thereby promoting the production of functional proteins. Gene therapy, such as the use of adeno-associated virus vectors, involves delivering healthy copies of genes to replace or repair the faulty ones in patients' cells. These approaches are crucial for muscular disorder patients as they address the root cause of the disease, potentially leading to more effective and long-lasting treatments compared to traditional therapies that only manage symptoms.

What side effects are associated with this type of intervention?

RNA modulation and gene therapy treatments for muscular disorders, such as those being studied in the AOC 1001 trial, often aim to correct or mitigate genetic defects at the molecular level. Common side effects of these treatments can include injection site reactions, immune responses, and off-target effects that may lead to unintended tissue damage. Long-term safety data is still being gathered, but potential risks include the development of malignancies or other unforeseen genetic complications. Patients undergoing these treatments should be closely monitored for both immediate and delayed adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for muscular disorders that involve RNA modulation or gene therapy. For Duchenne Muscular Dystrophy (DMD), therapies such as exon-skipping drugs (e.g., eteplirsen) have been approved, which work by modifying RNA to produce functional dystrophin protein. Additionally, gene therapy approaches, including the use of adeno-associated virus (AAV) vectors to deliver micro-dystrophin genes, are under investigation. For Myotonic Dystrophy Type 1 (DM1), ongoing trials like AOC 1001 focus on RNA modulation to address the underlying genetic defects. These treatments aim to correct or mitigate the effects of genetic mutations at the RNA level, offering potential disease-modifying benefits.

What other types of research exist?

Promising alternatives to AOC 1001 for muscular disorders include: 1) Antisense oligonucleotide (AON) therapies, such as those targeting dystrophin exon skipping, which have shown efficacy in dystrophic mouse models. 2) Combined exon-skipping therapies for dystrophin restoration and myostatin inhibition, which have demonstrated improved muscle pathology in mdx mice. 3) Oral administration of nanoparticle-AON complexes encapsulated with alginate, which has induced dystrophin rescue in mdx mice. These alternatives are in various stages of research and may offer new treatment options in the near future.

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Antisense Oligonucleotide

AOC 1001 for Myotonic Dystrophy (MARINA-OLE Trial)

Phase 2

Waitlist Available

Research Sponsored by Avidity Biosciences, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through study completion, up to week 248

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Specific side effects aren't listed here but generally may include reactions at the infusion site, potential allergic responses to AOC 1001, general discomforts like headaches or nausea, and any other unexpected health changes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through study completion, up to week 248

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through study completion, up to week 248

This trial's timeline: 3 weeks for screening, Varies for treatment, and through study completion, up to week 248 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Plasma pharmacokinetic (PK) parameters

Trial Design

2Treatment groups

Experimental Treatment

Group I: AOC 1001 (with Placebo at Day 43)Experimental Treatment2 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 1001Experimental Treatment1 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Placebo

1995

Completed Phase 3

~2670

AOC 1001

2021

Completed Phase 2

~40

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for muscular disorders, such as RNA modulation and gene therapy, work by targeting the genetic and molecular basis of these conditions. RNA modulation, including antisense oligonucleotides like Tofersen, aims to correct or modify the expression of defective genes by binding to specific RNA sequences, thereby promoting the production of functional proteins. Gene therapy, such as the use of adeno-associated virus vectors, involves delivering healthy copies of genes to replace or repair the faulty ones in patients' cells. These approaches are crucial for muscular disorder patients as they address the root cause of the disease, potentially leading to more effective and long-lasting treatments compared to traditional therapies that only manage symptoms.

Fondazione Telethon and Unione Italiana Lotta alla Distrofia Muscolare, a successful partnership for neuromuscular healthcare research of value for patients.