Del-desiran for Myotonic Dystrophy

(HARBOR Trial)

Not currently recruiting at 46 trial locations

Overseen By Avidity Biosciences, Inc.

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Avidity Biosciences, Inc.

Must not be taking: Anti-myotonic medications

Disqualifiers: Pregnancy, Uncontrolled diabetes, Heart failure, others

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: 54 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called del-desiran for individuals with Myotonic Dystrophy Type 1, a condition that causes muscle weakness and stiffness. The trial aims to determine if del-desiran is safe and effective compared to a placebo (a substance with no active drug). Participants will receive the treatment or placebo seven times. Suitable candidates have a clinical and genetic diagnosis of Myotonic Dystrophy Type 1 and can walk at least 10 meters unassisted. As a Phase 3 trial, this is the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anti-myotonic medications at least 14 days before starting the study or longer, depending on how long the medication stays in your body.

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. In one study, 37 participants received over 265 doses of del-desiran. The drug proved safe, with only mild side effects such as nausea and headache. No serious safety issues emerged. These results suggest that the treatment is safe for people with myotonic dystrophy. ^{1 2 3 4 5}

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

Del-desiran is unique because it targets myotonic dystrophy type 1 (DM1) at its genetic roots, aiming to reduce the toxic RNA that causes the disease. Unlike existing treatments that mainly address symptoms, Del-desiran, also known as AOC 1001, uses an innovative approach by combining an antibody with a small interfering RNA to specifically target and degrade the harmful RNA in muscle cells. This targeted mechanism has the potential to improve muscle function more effectively and with fewer side effects than current options, which include physical therapy and medications that manage symptoms like muscle stiffness and pain. Researchers are excited because this could lead to a more direct and effective treatment for DM1, potentially altering the course of the disease itself.

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

Research shows that del-desiran, which participants in this trial may receive, has promising results for treating myotonic dystrophy type 1 (DM1). Studies have found that del-desiran reduces muscle stiffness and improves muscle strength. Specifically, patients who received 4 mg/kg of del-desiran every three months experienced consistent and lasting improvements over a year. These findings suggest that del-desiran could be an effective treatment for DM1, a progressive disease with no approved treatments. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals who can walk independently (with orthoses and ankle braces allowed) at least 10 meters and have a clinical and genetic diagnosis of Myotonic Dystrophy Type 1 with CTG repeat ≥ 100. It's not specified who cannot join.

Inclusion Criteria

I can walk by myself for at least 10 meters, even with supports like braces.

I have been diagnosed with DM1 and my genetic test shows CTG repeat ≥ 100.

Exclusion Criteria

I cannot or will not follow the birth control requirements.

My diabetes is not well-controlled.

Body Mass Index > 35 kg/m2 at Screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 6 weeks

Treatment

Participants receive an intravenous infusion of either del-desiran or placebo every 8 weeks for a total of 7 doses

54 weeks

7 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

Open-label extension (optional)

Eligible participants may opt into continuation of treatment long-term, pending regulatory approval

What Are the Treatments Tested in This Trial?

Interventions

• Del-desiran

Trial Overview The study tests the efficacy and safety of an intravenous drug called del-desiran, compared to a placebo in treating Myotonic Dystrophy Type 1. This phase 3 trial is randomized, meaning participants are randomly assigned to groups, and double-blind, so neither researchers nor participants know who gets the real treatment.

How Is the Trial Designed?

Group I: Del-desiran Experimental Treatment 1 Intervention

Del-desiran (AOC 1001) will be administered seven times

Group II: Placebo Placebo Group 1 Intervention

Saline will be administered seven times

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

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. musculardystrophynews.com musculardystrophynews.com/del-desiran-for-myotonic-dystrophy-type-1/

Del-desiran for myotonic dystrophy type 1 At one year, treatment with 4 mg/kg of del-desiran once every three months continued to be safe and effective, reducing myotonia, and improving ...

5. neurologylive.com neurologylive.com/view/fda-removes-partial-hold-myotonic-dystrophy-agent-aoc-1001

FDA Removes Partial Hold for Myotonic Dystrophy Agent ... AOC 1001, also known as del-desiran, has shown promising results in improving muscle strength and reducing myotonia in patients with DM1 ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07008469

NCT07008469 | Global Open-Label Extension Study of Del ... Del-desiran (AOC 1001) will be administered seven times per year for up to 4 years. Intervention/Treatment, Drug : Del-desiran (AOC 1001).