Del-desiran for Myotonic Dystrophy

(HARBOR-OLE Trial)

Enrolling by invitation at 8 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Avidity Biosciences, Inc.

Disqualifiers: Pregnancy, Non-compliance, New conditions, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 7

Duration: 4 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment called del-desiran to assess its safety and effectiveness for individuals with myotonic dystrophy type 1, a condition that causes muscle weakness and stiffness. Participants will receive this treatment through an IV several times a year for up to four years. Suitable candidates for this trial have already participated in previous studies with del-desiran and completed all required steps. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I have to stop taking my current medications for the trial?

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

Is there any evidence suggesting that del-desiran is likely to be safe for humans?

Research has shown that del-desiran is generally well-tolerated by people with myotonic dystrophy type 1. In a previous study, participants experienced consistent and lasting improvements without major safety issues. Another study, conducted after one year of treatment, showed positive results, such as improved muscle strength and reduced hand stiffness. These findings suggest that del-desiran might be safe for long-term use.

For those considering joining a trial, these results indicate that the treatment has undergone safety testing in humans. However, it is important to consult a healthcare professional about any concerns. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Del-desiran is unique because it targets the root cause of myotonic dystrophy by using an innovative mechanism called RNA interference. Unlike current treatments that mainly focus on managing symptoms, Del-desiran aims to reduce the production of toxic RNA that underlies the disease. This targeted approach has the potential to not only alleviate symptoms but also slow disease progression, which is why researchers are excited about its possibilities.

What evidence suggests that del-desiran might be an effective treatment for myotonic dystrophy?

Research has shown that del-desiran, the treatment under study in this trial, may help treat myotonic dystrophy type 1 (DM1). In the MARINA-OLE study, del-desiran consistently improved patients' conditions over time. The study found that it could reverse the progression of the disease in several ways. Specifically, patients experienced better muscle function and fewer symptoms as time progressed. These results suggest that del-desiran might effectively slow down or improve DM1 in patients. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals who have completed previous AOC 1001 studies for Myotonic Dystrophy Type 1 and met all requirements. Participants must not be pregnant, breastfeeding, or planning to become pregnant and must agree to use contraception during the study.

Inclusion Criteria

Completion of any prior AOC 1001 studies with satisfactory completion of dosing and follow-up assessments and satisfactory compliance with the protocol requirements of the parent study, as determined by the Investigator.

Exclusion Criteria

Breastfeeding, pregnancy, or intent to become pregnant during the study

I am not willing to follow the birth control requirements.

Any new conditions or worsening of existing condition that in the opinion of the Investigator would make the participant unsuitable for the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4-8 weeks

Treatment

Participants receive an intravenous infusion of del-desiran every 8 weeks for up to 4 years

4 years

7 visits per year (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the final dose

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Del-desiran

Trial Overview The trial is testing the long-term safety and effectiveness of Del-desiran (AOC 1001) administered intravenously in patients with Myotonic Dystrophy Type 1. It's an extension study following earlier phases.

How Is the Trial Designed?

Group I: Del-desiran Experimental Treatment 1 Intervention

Del-desiran (AOC 1001) will be administered seven times per year for up to 4 years.

Who Is Running the Clinical Trial?

Avidity Biosciences, Inc.

Lead Sponsor

Trials

8

Recruited

960+

Citations

1. aviditybiosciences.com aviditybiosciences.com/pipeline/dm1

Pipeline DM1 MARINA-OLE™ is an open-label, multi-center trial designed to evaluate the long-term safety and tolerability of del-desiran in participants with myotonic ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06411288

Global Study of Del-desiran for the Treatment of DM1 A Phase 3 Randomized, Double-Blind, Placebo-Controlled, Global Study to Evaluate the Efficacy and Safety of Intravenous Delpacibart Etedesiran

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

March 4, 2024 In the MARINA-OLE study, del-desiran (AOC 1001) 4 mg/kg data demonstrated consistent and long-lasting improvements in the following ...

4. medthority.com medthority.com/news/2024/3/positive-aoc-1001-long-term-data-showing-reversal-of-disease-progression-in-people-living-with-myotonic-dystrophy-type-1-across-multiple-endpoints-same-key-endpoints-agreed-for-phase-iii-harbor-trial.--avidity--biosciences

Positive AOC 1001 long-term data showing reversal of ... Long-term del-desiran (AOC 1001) data from the MARINA-OLE study show reversal of disease progression in people living with DM1 across multiple ...

5. neurologylive.com neurologylive.com/view/avidity-begin-phase-3-harbor-trial-myotonic-dystrophy-positive-marina-results

Avidity to Begin Phase 3 HARBOR Trial in Myotonic ... "The long-term data from the MARINA-OLE study demonstrating that del-desiran improved measures of disease progression in DM1 patients compared ...

6. institut-myologie.org institut-myologie.org/en/2024/04/25/aoc-1001-in-dm1-positive-data-after-one-year-of-treatment-in-the-marina-trial/

positive data after one year of treatment in the MARINA trial AOC 1001 in DM1: positive data after one year of treatment in the MARINA trial · a significant improvement in hand myotonia, muscular strength ...

7. nmd-journal.com nmd-journal.com/article/S0960-8966(23)00667-3/fulltext

O18 Topline safety and efficacy data analysis of phase 1/2 ... The primary objective is to present the safety, tolerability, and efficacy of single and multiple ascending doses of AOC 1001 in adults with myotonic ...