AOC 1044 for Duchenne Muscular Dystrophy

(EXPLORE44 Trial)

No longer recruiting at 10 trial locations

Overseen By Avidity Biosciences, Inc.

Age: < 65

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Avidity Biosciences, Inc.

Must be taking: Corticosteroids

Must not be taking: Exon 44 agents

Disqualifiers: Hypertension, Diabetes, Drug allergies, others

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, AOC 1044, to assess its safety and tolerability for people with Duchenne Muscular Dystrophy (DMD), particularly those with genetic mutations that may benefit from exon 44 skipping. The trial explores different dosages to determine the most effective one. Healthy adults and those with DMD might be eligible, especially if they have experienced DMD symptoms since age six or earlier and have a specific genetic profile. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group. Participants have the opportunity to be among the first to benefit from this promising new therapy.

Will I have to stop taking my current medications?

For Part A, participants must not have used prescription or nonprescription drugs recently. For Part B, if you are on corticosteroids, you need to be on a stable dose for 30 days before the study and throughout its duration.

Is there any evidence suggesting that AOC 1044 is likely to be safe for humans?

Research has shown that AOC 1044 has undergone testing to assess its safety for humans. In one study with a 5 mg/kg dose, patients showed a significant increase in dystrophin production, indicating potential treatment efficacy. While this result does not directly confirm safety, it suggests a positive effect on the body.

AOC 1044 is currently in the early testing stages (Phase 1/2). Researchers are closely monitoring how well participants tolerate the treatment and any side effects that may occur. This phase aims to determine safety, though detailed safety information is not yet fully available. Early trials are designed to carefully monitor and manage any adverse effects. Participants must report any side effects they experience during these trials. ^{1 2 3 4 5}

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

Researchers are excited about AOC 1044 because it offers a new approach to treating Duchenne Muscular Dystrophy (DMD). Most treatments for DMD focus on managing symptoms or slowing muscle degeneration. However, AOC 1044 works differently by using an innovative mechanism called "RNA-targeted therapy" to address the root genetic causes of the disease. This treatment has the potential to target the underlying issues in the muscle cells more directly, which could lead to more effective management of the condition. Additionally, AOC 1044's delivery method allows it to be administered in a way that might enhance its effectiveness and reduce side effects compared to traditional treatments.

What evidence suggests that AOC 1044 might be an effective treatment for Duchenne Muscular Dystrophy?

Research shows that AOC 1044, which participants in this trial may receive, could be a promising treatment for Duchenne Muscular Dystrophy (DMD). Studies have found that this treatment aids in exon 44 skipping, potentially restoring dystrophin, a crucial protein for muscle function. In some patients, AOC 1044 increased dystrophin production to 25% of normal levels, marking a significant improvement. This suggests that AOC 1044 might enhance muscle function in individuals with certain DMD mutations. Early data from lab studies also support these findings, demonstrating positive changes in muscle tissue. ^{1 3 4 5 6}

Who Is on the Research Team?

Carmen Castrillo, MD

Principal Investigator

Avidity Biosciences, Inc.

Are You a Good Fit for This Trial?

This trial is for healthy adults and those with Duchenne Muscular Dystrophy (DMD) who can benefit from exon 44 skipping. Participants must be aged 18-55 years with a BMI of 18.5 to 32 kg/m2.

Inclusion Criteria

I weigh at least 23 kg.

I was diagnosed with DMD or showed symptoms by age 6.

Part A: Body mass index (BMI) of 18.5 to 32.0 kg/m2

Exclusion Criteria

I have previously undergone cell or gene therapy.

Part B: Serum hemoglobin < lower limit of normal

My biceps muscles cannot be biopsied.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Single dose administration of AOC 1044 or placebo in healthy adult volunteers

8 weeks

Multiple visits for dose administration and monitoring

Treatment Part B

Multiple ascending dose administration of AOC 1044 or placebo in participants with DMD

12 weeks

Multiple visits for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• AOC 1044

Trial Overview The study tests AOC 1044, which could potentially treat DMD by skipping exon 44 in the gene mutation. It's given in single or multiple doses to see how safe it is and how the body responds.

How Is the Trial Designed?

Group I: AOC 1044-CS1 Part B - Multiple Ascending Dose Levels 1-3 Experimental Treatment 1 Intervention

AOC 1044 will be administered three times.

Group II: AOC 1044-CS1 Part A - Single Dose Levels 1-5 Experimental Treatment 1 Intervention

AOC 1044 will be administered once.

Group III: AOC 1044-CS1 Part A - Single Dose: Placebo Placebo Group 1 Intervention

Placebo will be administered once.

Group IV: AOC 1044-CS1 Part B - Multiple Ascending Dose: Placebo Placebo Group 1 Intervention

Placebo will be administered three times.

Who Is Running the Clinical Trial?

Avidity Biosciences, Inc.

Lead Sponsor

Trials

8

Recruited

960+

Citations

1. aviditybiosciences.com aviditybiosciences.com/sites/default/files/2025-10/Flanigan%20WMS%202025%20EXPLORE44%20Functional%20Oral%20Presentation.pdf

Delpacibart zotadirsen (Del-zota) Showed Trends for ... Participants at 10 mg/kg Q8W in EXPLORE44® were transitioned to 5 mg/kg Q6W. DMD44, Duchenne muscular dystrophy with mutations amenable to exon ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11969676/

AOC 1044 induces exon 44 skipping and restores ... AOC 1044 induces exon 44 skipping and restores dystrophin protein in preclinical models of Duchenne muscular dystrophy.

3. parentprojectmd.org parentprojectmd.org/avidity-biosciences-announces-positive-data-from-phase-1-2-explore44-trial-of-aoc-1044-in-individuals-amenable-to-exon-44-skipping/

Avidity Biosciences Announces Positive Data From Phase ... Data from the 5mg/kg cohort of AOC 1044 at four months demonstrated statistically significant increase of 25% of normal in dystrophin production ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06244082?term=aoc%201044

Ph2 Open-label Study of AOC 1044 in Duchenne Muscular ... AOC 1044 -CS2 (EXPLORE44-OLE) is an Open-label Study to Evaluate the Long-Term Safety and Tolerability of AOC 1044 Administered Intravenously to DMD ...

5. mdaconference.org mdaconference.org/abstract-library/del-zota-produced-statistically-significant-increases-in-exon-skipping-and-dystrophin-levels-in-explore44-a-phase-1-2-study-in-patients-with-dmd44/

Del-zota produced statistically significant increases in exon ... Treatment with del-zota produced statistically significant increases in exon skipping and dystrophin production in skeletal muscle and significant reductions ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05670730

NCT05670730 | Study of AOC 1044 in Healthy Adult ... A Phase 1/2 study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of single and multiple ascending doses of AOC 1044 in ...