AOC 1044 for Duchenne Muscular Dystrophy

(EXPLORE44OLE Trial)

Not currently recruiting at 10 trial locations

Overseen By Avidity Biosciences, Inc. Patient Advocacy

Age: < 65

Sex: Male

Trial Phase: Phase 2

Sponsor: Avidity Biosciences, Inc.

Must be taking: Corticosteroids

Must not be taking: Investigational drugs

Disqualifiers: Uncontrolled hypertension, diabetes, 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: 6

Duration: 104 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and tolerability of a new treatment called AOC 1044 for individuals with Duchenne Muscular Dystrophy (DMD), a genetic disorder that causes muscle weakness. Participants will receive AOC 1044 through an IV every six weeks for about two years. The trial targets individuals with a specific gene mutation that can benefit from exon 44 skipping, a technique that helps a missing part of a gene function properly. Eligible participants should have shown DMD symptoms before age 6, have a confirmed mutation, and be able to walk or use a wheelchair. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on corticosteroids, you must be on a stable dose for 30 days before screening and throughout the study.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but if you are on corticosteroids, you must be on a stable dose for 30 days before screening and throughout the study.

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

Research has shown that AOC 1044 offers promising results for treating Duchenne Muscular Dystrophy. In earlier studies, patients who received AOC 1044 showed a significant increase in dystrophin, a protein crucial for muscle health, indicating that the treatment effectively reaches its target.

Safety data from past trials indicate that participants have tolerated AOC 1044 well. These studies reported no severe side effects. While minor side effects can occur in any trial, no major safety concerns have emerged for AOC 1044.

AOC 1044 has undergone several rounds of human testing, providing extensive safety information. This supports the treatment's safety for further research and use in clinical trials. ^{1 2 3 4 5}

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

AOC 1044 is unique because it introduces a novel approach to treating Duchenne Muscular Dystrophy (DMD). Unlike traditional treatments that mainly focus on managing symptoms or slowing progression, AOC 1044 uses an innovative mechanism by delivering its active components via intravenous infusion every six weeks. This method aims to target the underlying genetic causes of DMD more directly. Researchers are excited about AOC 1044 because it holds the potential to offer more sustained and effective results over the long term compared to current options, which often require more frequent administration and focus primarily on symptom management.

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

Research shows that AOC 1044, administered at multiple dose levels in this trial, may help treat Duchenne Muscular Dystrophy (DMD) in patients with certain genetic mutations. Studies have found that AOC 1044 can increase dystrophin production to 25% of normal levels. Dystrophin, a crucial protein, protects muscle cells, and its deficiency is a major issue in DMD. AOC 1044 works by skipping a part of the gene called exon 44, enabling cells to produce more functional dystrophin. Early tests in models also support these findings, demonstrating that AOC 1044 can restore dystrophin in muscle tissue. Overall, initial data suggest that AOC 1044 could be a promising treatment for people with DMD due to exon 44 mutations. ^{1 2 4 6 7}

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 individuals with Duchenne Muscular Dystrophy (DMD) who have specific genetic mutations that can be treated by skipping exon 44. Participants must have completed a prior study, EXPLORE44, without significant issues tolerating the treatment.

Inclusion Criteria

I have not had major side effects from AOC 1044.

I successfully finished the EXPLORE44 study as approved by my doctor and the study sponsor.

Exclusion Criteria

Presence of any new condition or worsening of existing condition that could affect a participant's safety or ability to comply with study procedures

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AOC 1044 intravenously every 6 or 8 weeks for approximately 2 years

104 weeks

IV dosing every 6 or 8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Open-label extension

Participants may continue to receive treatment beyond 2 years if the sponsor extends the study

What Are the Treatments Tested in This Trial?

Interventions

• AOC 1044

Trial Overview The trial is testing AOC 1044, an intravenous medication designed to skip exon 44 in DMD patients. It aims to assess the drug's long-term safety and its effect on the body over time in an open-label setting.

How Is the Trial Designed?

Group I: AOC 1044 Multiple Dose Levels Experimental Treatment 1 Intervention

AOC 1044 will be IV infused every 6 weeks for approximately 2 years.

Who Is Running the Clinical Trial?

Avidity Biosciences, Inc.

Lead Sponsor

Trials

8

Recruited

960+

Published Research Related to This Trial

Antisense oligonucleotides (AOs) targeting dystrophin through a method called exon skipping show promise as a treatment for Duchenne muscular dystrophy (DMD), with an AO for skipping exon 51 already receiving accelerated approval in the USA.

The study emphasizes the need for combined therapies, especially in older DMD patients, and outlines a methodology for delivering AOs in a mouse model to enhance muscle size and strength by targeting both dystrophin and myostatin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Intravenous Administration of Antisense Therapeutics for Combinatorial Dystrophin and Myostatin Exon Splice Modulation. Lu-Nguyen, N., Dickson, G., Malerba, A.[2019]

Antisense oligonucleotide (AO)-mediated exon skipping therapy for Duchenne muscular dystrophy (DMD) has shown promising results, with significant contributions from Japanese patients leading to its development and proof of concept.

The therapy has been validated in multiple cases, including a patient with a nonsense mutation and another with an exon deletion, paving the way for over 300 published studies on its efficacy and potential for marketing authorization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contributions of Japanese patients to development of antisense therapy for DMD. Matsuo, M., Takeshima, Y., Nishio, H.[2016]

In a study involving 233 children aged 4-11 years with mild-to-moderate persistent asthma, both doses of mometasone furoate (MF-DPI) were found to be well tolerated over 52 weeks, showing a similar safety profile to beclomethasone dipropionate (BDP-MDI).

The most common adverse events were upper respiratory tract infections, with no significant safety concerns or clinically relevant changes in laboratory values, indicating that both treatments are safe options for managing asthma in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety of mometasone furoate administered via a dry powder inhaler in children: Results of an open-label study comparing mometasone furoate with beclomethasone dipropionate in children with persistent asthma. Noonan, M., Leflein, J., Corren, J., et al.[2021]

A new cellular model using MYOD1-transduced urine-derived cells (MYOD1-UDCs) from DMD patients shows significantly better efficiency for exon skipping compared to traditional rhabdomyosarcoma cells, making it a more relevant system for drug screening.

The study highlights that the effectiveness of exon skipping varies based on the specific DMD mutation, and that the sequence of the antisense oligonucleotide eteplirsen is less effective than other tested sequences, emphasizing the need for optimization in drug design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highly sensitive screening of antisense sequences for different types of DMD mutations in patients' urine-derived cells. Takizawa, H., Takeshita, E., Sato, M., et al.[2021]

Inhaled corticosteroids like beclometasone-dipropionate (BDP) and formoterol show nearly double the systemic exposure in children compared to adults, despite children receiving half the adult dose, indicating a need for careful dosing in younger patients.

The study suggests that dosage regimens for inhaled medications should be adjusted based on age and body size to prevent excessive systemic drug levels in children, as systemic exposure inversely correlates with these factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic exposure to inhaled beclometasone/formoterol DPI is age and body size dependent. Chawes, BL., Govoni, M., Kreiner-Møller, E., et al.[2015]

In a Phase II study involving 610 patients with poorly-controlled asthma, beclomethasone dipropionate (BDP) at a dose of 200 µg twice daily significantly improved lung function compared to placebo, with an increase in pre-dose morning FEV1 of 113 ml after 8 weeks.

The study found that BDP 200 µg BID provided the best balance of efficacy and safety, with adverse event rates similar to those of the placebo and active comparator, indicating it is a suitable option for patients inadequately controlled on low/medium-dose inhaled corticosteroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of inhaled extrafine beclomethasone dipropionate in adults with asthma: a randomized, parallel-group, dose-ranging study (BEAM). Montanaro, A., Weinstein, S., Beaudot, C., et al.[2022]

Exon skipping shows potential as a treatment for Duchenne muscular dystrophy, which is a serious genetic disorder affecting muscle function.

However, the path to getting these therapies approved is complicated and may need more early testing and clearer regulatory support to ensure safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exon-skipping therapy: a roadblock, detour, or bump in the road? Hoffman, EP., McNally, EM.[2021]

In a study involving 395 adults with moderate persistent asthma, mometasone furoate (MF) administered via metered dose inhaler showed significant improvements in lung function (FEV1) compared to placebo, with all doses (56, 200, and 500 micrograms) being effective.

Mometasone furoate 200 micrograms b.i.d. was found to be more effective than beclomethasone dipropionate (BDP) 168 micrograms b.i.d., indicating that MF-MDI may offer superior efficacy for asthma management without additional benefits from higher doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of mometasone furoate administered by metered dose inhaler with beclomethasone dipropionate. Chervinsky, P., Nelson, HS., Bernstein, DI., et al.[2015]

Patients with Duchenne muscular dystrophy (DMD) who have deletions skippable for exon 44 or 45 show some dystrophin expression, but at lower levels compared to those with exon 51 deletions, suggesting exon 51 skipping may be more effective in producing functional dystrophin.

The study indicates that dystrophin transcript stability is a key factor in predicting dystrophin expression levels, with unstable transcripts in DMD patients potentially serving as a biomarker for response to antisense oligonucleotide treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biochemical characterization of patients with in-frame or out-of-frame DMD deletions pertinent to exon 44 or 45 skipping. Anthony, K., Arechavala-Gomeza, V., Ricotti, V., et al.[2022]

Antisense oligonucleotides (AOs) can effectively induce exon skipping in the DMD gene, potentially allowing for the production of a functional dystrophin protein in patients with Duchenne muscular dystrophy (DMD).

The development of personalized AOs tailored to specific mutations in the DMD gene is crucial, as different mutations require different exons to be skipped for effective treatment, indicating a need for extensive optimization and clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing antisense oligonucleotides using phosphorodiamidate morpholino oligomers. Popplewell, LJ., Malerba, A., Dickson, G.[2012]

In a Phase 2 study involving 51 ambulant Duchenne muscular dystrophy (DMD) patients, drisapersen at a dose of 6 mg/kg/week showed a potential benefit in improving the 6-minute walking distance (6MWD) compared to placebo, with a mean difference of 27.1 meters at week 24.

Drisapersen was generally well-tolerated, with the most common side effects being injection site reactions and subclinical proteinuria, indicating a manageable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy. McDonald, CM., Wong, B., Flanigan, KM., et al.[2022]

In a six-month trial involving asthmatics who required oral corticosteroids, a high dose of 2,000 micrograms per day of beclomethasone dipropionate (BDP) significantly reduced oral steroid requirements by 57%, compared to a 34% reduction in the standard 800 microgram dose group.

The high dose BDP not only maintained good asthma control but also improved pulmonary function and baseline serum cortisol levels, indicating its safety and efficacy in managing long-term steroid-dependent asthma without increasing the risk of side effects like dysphonia or oropharyngeal candidiasis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six-month double-blind, controlled trial of high dose, concentrated beclomethasone dipropionate in the treatment of severe chronic asthma. Tarlo, SM., Broder, I., Davies, GM., et al.[2019]

In a study involving 53 boys with Duchenne muscular dystrophy, continuous treatment with drisapersen for 48 weeks led to a significant improvement in walking distance (6-minute walk distance) compared to placebo, with an increase of 31.5 meters at week 25.

The safety profile of drisapersen was generally acceptable, with common side effects including injection-site reactions and mild renal events, none of which led to study withdrawal, indicating that the treatment is relatively safe for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of drisapersen for the treatment of Duchenne muscular dystrophy (DEMAND II): an exploratory, randomised, placebo-controlled phase 2 study. Voit, T., Topaloglu, H., Straub, V., et al.[2022]

Golodirsen was found to be well-tolerated in patients with Duchenne muscular dystrophy (DMD), with safety results consistent with previous studies in pediatric patients.

Treatment with golodirsen led to a significant increase in exon 53 skipping and a 16-fold increase in dystrophin protein expression at week 48, indicating its potential efficacy in restoring dystrophin production in muscle tissue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Frank, DE., Schnell, FJ., Akana, C., et al.[2023]

The study developed shorter 25-mer phosphorodiamidate morpholino oligonucleotides (PMOs) that can effectively induce dystrophin restoration in Duchenne muscular dystrophy (DMD), showing comparable efficacy to the longer 30-mer PMO eteplirsen.

Using shorter PMOs could allow for higher dosing, which enhances drug uptake into muscle fibers, potentially leading to greater dystrophin restoration and improved clinical outcomes for patients with DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Shorter Phosphorodiamidate Morpholino Splice-Switching Oligonucleotides May Increase Exon-Skipping Efficacy in DMD. Akpulat, U., Wang, H., Becker, K., et al.[2021]

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. 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 ...

3. 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.

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. prnewswire.com prnewswire.com/news-releases/avidity-biosciences-announces-positive-aoc-1044-data-demonstrated-significant-increase-of-25-in-dystrophin-production-and-reduction-of-creatine-kinase-levels-to-near-normal-in-people-living-with-duchenne-muscular-dystrophy-amenab-302218647.html

Avidity Biosciences Announces Positive AOC 1044 Data ... Delpacibart zotadirsen (AOC 1044) delivered unsurpassed muscle concentrations of PMO of 200 nM after three doses of 5 mg/kg.

7. cgtlive.com cgtlive.com/view/del-zota-duchenne-muscular-dystrophy

Del-Zota for Duchenne Muscular Dystrophy The investigational antisense treatment, which is in development for DMD amenable to exon 44 skipping.