RGX-202 Gene Therapy for Duchenne Muscular Dystrophy

Recruiting at 16 trial locations

Overseen By Aravindhan Veerapandiyan, MD

Age: Any Age

Sex: Male

Trial Phase: Phase 2 & 3

Sponsor: REGENXBIO Inc.

Must be taking: Systemic glucocorticoids

Must not be taking: Ataluren, Exon-skipping therapy

Disqualifiers: Gene therapy, Cardiac dysfunction, 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: 1

Duration: 1 day

65 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy called RGX-202 to treat Duchenne muscular dystrophy (DMD), a condition that weakens muscles over time. The therapy delivers a special gene to produce a protein similar to the one missing in people with DMD. The study will determine if a one-time IV dose is safe and effective in improving muscle function. Boys with DMD who can walk specific distances without assistance and have not recently used certain other treatments might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking advancements in DMD therapy.

Will I have to stop taking my current medications?

Participants must stop taking certain medications like ataluren or exon-skipping therapies for 5 years after receiving RGX-202. If taking vamorolone, it must be switched to prednisolone or prednisone before the study and can be resumed 12 weeks after RGX-202 dosing.

Is there any evidence suggesting that RGX-202 is likely to be safe for humans?

Research has shown that RGX-202 appears safe in studies. Early findings suggest participants generally handled the gene therapy well, with no major safety issues reported so far.

RGX-202 aims to help people with Duchenne muscular dystrophy by providing a special gene. This gene helps produce a protein called microdystrophin, similar to the one missing in people with this condition. The treatment is administered as a one-time IV drip.

While these early results are encouraging, it's important to remember that this treatment remains under study. Joining a clinical trial can help researchers learn more about its safety and effectiveness. ^{1 2 3 4 5}

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

Most treatments for Duchenne Muscular Dystrophy, such as corticosteroids or exon-skipping drugs, work by managing symptoms or helping specific genetic mutations. But RGX-202 works differently, targeting the root cause by delivering a healthy copy of the dystrophin gene directly to the muscles through gene therapy. This innovative approach could potentially restore the production of functional dystrophin protein, which is crucial for muscle strength and function. Researchers are excited because this method has the potential to provide a more lasting and comprehensive improvement in muscle health compared to existing treatments, which mainly focus on symptom management.

What evidence suggests that RGX-202 might be an effective treatment for Duchenne?

Studies have shown that RGX-202, a new gene therapy, holds promise for treating Duchenne muscular dystrophy. Research indicates that it can enhance patient function and positively alter the disease's progression. In this trial, participants will receive varying doses of RGX-202. Initial findings suggest that higher doses are particularly effective, with participants demonstrating noticeable improvements. This therapy delivers a special gene that aids in producing microdystrophin, a protein lacking in individuals with Duchenne. By increasing this protein, RGX-202 aims to support muscle health and slow the disease's progression. Early results are encouraging, with positive changes in disease markers and patient abilities. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for individuals with Duchenne Muscular Dystrophy (DMD) who have a specific gene mutation, can walk 100 meters without help, and have been on stable glucocorticoids for at least 12 weeks. They must not have had other gene therapies or certain DMD treatments recently and should not need to avoid immunosuppression.

Inclusion Criteria

I can walk 100 meters on my own without help.

I have been on a stable dose of steroids for at least 12 weeks before my recent tests.

My liver and kidney tests are normal or not concerning.

Exclusion Criteria

Participant has received any investigational or commercial gene therapy product over his lifetime

Participant is currently taking any other investigational intervention or has taken any other investigational intervention within 3 months prior to the scheduled Day 1 intervention

Participant has detectable AAV8 total binding antibodies in serum

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time intravenous dose of RGX-202 gene therapy

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, tolerability, and efficacy of RGX-202

52 weeks

Multiple visits (in-person and virtual)

Long-term follow-up

Participants are assessed for long-term safety and efficacy of RGX-202

104 weeks

Open-label extension (optional)

Participants may opt into a separate long-term follow-up study

What Are the Treatments Tested in This Trial?

Interventions

• RGX-202

Trial Overview The trial tests RGX-202, a one-time IV gene therapy aimed at delivering a microdystrophin transgene to treat DMD. It's an open-label study evaluating the safety, tolerability, and effectiveness of this new treatment in participants.

How Is the Trial Designed?

Group I: Part 1: Cohort 2, 2c;, and Part 2; and Part 3: RGX-202 Dose 2 Experimental Treatment 1 Intervention

A single IV infusion of RGX-202 at a dose of 2x10\^14 GC/kg body weight

Group II: Part 1: Cohort 1 and 1b: RGX-202 Dose 1 Experimental Treatment 1 Intervention

A single IV infusion of RGX-202 at a dose of 1×10\^14 GC/kg body weight

Who Is Running the Clinical Trial?

REGENXBIO Inc.

Lead Sponsor

Trials

25

Recruited

3,100+

Published Research Related to This Trial

The study successfully demonstrated that regional vascular delivery of rAAV8 and rAAV6 carrying micro-dystrophin significantly improved muscle transduction efficiency in mdx mice, achieving over 89% transduction after three months, which is crucial for potential gene therapy in Duchenne muscular dystrophy (DMD).

The promising results in mice were translated to non-human primates, showing effective gene expression in multiple muscles, indicating that this delivery method could be adapted for clinical trials in children with DMD, enhancing the safety and efficacy of gene therapy approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy. Rodino-Klapac, LR., Janssen, PM., Montgomery, CL., et al.[2018]

Current therapies for Duchenne muscular dystrophy (DMD) include gene therapy, cell therapy, and pharmacological therapy, each targeting different aspects of the disease's progression.

Despite advancements, there is still no cure for DMD due to challenges in gene replacement and the complex nature of the symptoms, highlighting the need for more effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of therapy for Duchenne muscular dystrophy. Zhang, S., Xie, H., Zhou, G., et al.[2012]

The study demonstrated that a recombinant adeno-associated virus vector (rAAV8) carrying a modified U7snRNA sequence is safe for use in treating Duchenne muscular dystrophy (DMD) in 18 Golden Retriever Muscular Dystrophy (GRMD) dogs, with no adverse effects observed.

A dose-dependent response was noted, with up to 80% of myofibers expressing dystrophin at the highest dose, indicating that a minimum threshold of dystrophin expression is necessary for therapeutic effects, supporting future trials in nonambulatory DMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant AAV for exon skipping in Duchenne patients. Le Guiner, C., Montus, M., Servais, L., et al.[2022]

A new adenoviral vector, which is modified to delete all viral open reading frames, successfully delivers a full-length dystrophin minigene, showing promise for treating Duchenne muscular dystrophy (DMD).

This modified vector demonstrated efficient gene transfer in both mdx mice and muscle fibers in vivo, indicating its potential for developing effective gene therapies for DMD and possibly other diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo expression of full-length human dystrophin from adenoviral vectors deleted of all viral genes. Haecker, SE., Stedman, HH., Balice-Gordon, RJ., et al.[2012]

High-capacity adenoviral vectors (HC-AdVs) are less cytotoxic than traditional adenoviral vectors and can effectively deliver RNA-guided CRISPR-Cas9 nucleases for gene editing in Duchenne muscular dystrophy (DMD).

Using HC-AdVs, researchers achieved up to 42% correction of defective DMD alleles in muscle cells, leading to the production of Becker-like dystrophins, which are crucial for muscle function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Capacity Adenoviral Vectors Permit Robust and Versatile Testing of DMD Gene Repair Tools and Strategies in Human Cells. Brescia, M., Janssen, JM., Liu, J., et al.[2021]

In adult mdx mice with existing muscle weakness, adenovirus-mediated dystrophin gene transfer showed a narrow therapeutic margin, where both toxicity and gene transfer efficiency were dependent on the dose of the vector used.

With optimal dosing and immunosuppressive therapy, the treatment successfully improved muscle strength and reduced disease progression over two months, highlighting its potential for treating Duchenne muscular dystrophy in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adenovirus-mediated dystrophin minigene transfer improves muscle strength in adult dystrophic (MDX) mice. Yang, L., Lochmuller, H., Luo, J., et al.[2021]

The study demonstrated that human dystrophin expressing chimeric (DEC) cell therapy is safe for long-term use, showing no complications or DNA damage in a mouse model of Duchenne muscular dystrophy (DMD) after 180 days post-administration.

Biodistribution analysis confirmed that DEC cells effectively targeted the heart, diaphragm, and gastrocnemius muscle while showing minimal presence in non-target organs, indicating a promising therapeutic approach for DMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Biodistribution and Safety of Human Dystrophin Expressing Chimeric Cell Therapy After Systemic-Intraosseous Administration to Duchenne Muscular Dystrophy Model. Siemionow, M., Brodowska, S., Langa, P., et al.[2022]

Duchenne muscular dystrophy (DMD) is a significant genetic disease targeted for gene therapy, with the defective dystrophin gene identified as a key focus for treatment development over the past 30 years.

Despite challenges like the gene's large size and the extensive muscle tissue involved, advancements in gene replacement therapy for DMD have been promising, with several groups preparing for imminent human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress toward Gene Therapy for Duchenne Muscular Dystrophy. Chamberlain, JR., Chamberlain, JS.[2022]

Gene therapy using adeno-associated virus (rAAV) to deliver mini/micro-dystrophin shows promise for treating Duchenne Muscular Dystrophy (DMD), but high doses of rAAV can lead to immune responses and liver toxicity, especially in older patients.

Research suggests that using utrophin, a protein similar to dystrophin, along with a novel MyoAAV delivery system, could enhance therapeutic effects while reducing the required rAAV dose, potentially making gene therapy safer and more effective for a broader range of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategies for Bottlenecks of rAAV-Mediated Expression in Skeletal and Cardiac Muscle of Duchenne Muscular Dystrophy. Li, N., Song, Y.[2022]

Duchenne muscular dystrophy (DMD) is a severe genetic disorder primarily affecting boys, leading to muscle degeneration and early death, highlighting the urgent need for effective treatments.

AAV-based gene therapy using shortened microdystrophin genes shows promise as a treatment for DMD, and the article advocates for using microdystrophin expression as a surrogate endpoint to facilitate accelerated approval in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Microdystrophin Expression as a Surrogate Endpoint for Duchenne Muscular Dystrophy Clinical Trials. Chamberlain, JS., Robb, M., Braun, S., et al.[2023]

The micro-dystrophin gene transfer using rAAVrh74.MHCK7 was found to be well tolerated in a phase 1/2a trial with four young patients, showing only mild to moderate adverse events and no serious complications over one year.

All patients demonstrated significant expression of micro-dystrophin in muscle fibers and improvements in functional measures, such as North Star Ambulatory Assessment scores and reduced creatine kinase levels, indicating potential benefits beyond standard care for Duchenne muscular dystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial. Mendell, JR., Sahenk, Z., Lehman, K., et al.[2021]

Citations

1. regenxbio.com regenxbio.com/getmedia/e16fcfde-2e79-4749-b2b6-da308267afa0/MDA-AFFINITY-DUCHENNE-2025.pdf?ext=.pdf

RGX-202, an investigational gene therapy for the treatment ... RGX-202, an investigational gene therapy for the treatment of Duchenne muscular dystrophy: interim clinical data. Carolina Tesi-Rocha, M.D.. Clinical ...

2. regenxbio.gcs-web.com regenxbio.gcs-web.com/news-releases/news-release-details/regenxbio-reports-new-positive-functional-data-phase-iii

REGENXBIO REPORTS NEW POSITIVE FUNCTIONAL ... RGX-202 demonstrating consistent evidence of positively changing disease trajectory for Duchenne. All dose level 2 participants exceeded ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05693142

RGX-202 Gene Therapy in Participants With Duchenne ... This is a multicenter, open-label dose evaluation clinical study to assess the safety, tolerability, and clinical efficacy of a one-time intravenous (IV) dose ...

4. regenxbio.com regenxbio.com/getattachment/235b264f-bf42-4278-b4f6-0f20735e0026/WMS-2025_RGX-202_Poster_vFinal.pdf?lang=en-US&ext=.pdf

RGX-202, an Investigational Gene Therapy for the ... Heterogeneity is present across baseline disease stage, rate of disease progression, and anticipated efficacy response.

5. ajmc.com ajmc.com/view/rgx-202-gene-therapy-improves-dmd-trajectory-biomarkers

RGX-202 Gene Therapy Improves DMD Trajectory ... - AJMC RGX-202 shows promising efficacy in Duchenne muscular dystrophy, improving functional outcomes and biomarker expression in early trial results.

6. neurology.org neurology.org/doi/10.1212/WNL.0000000000206682

RGX-202, an Investigational Gene Therapy for the ... Objective: To evaluate safety and efficacy of RGX-202 in patients with Duchenne muscular dystrophy (DMD) aged 4 to 11 years.