SRD-001 for Duchenne Muscular Dystrophy

(MUSIC-DMD Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Age: 18+

Sex: Male

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Sardocor Corp.

Must be taking: Cardiac medications, Glucocorticoids

Disqualifiers: Abnormal blood pressure, Liver issues, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This research study is testing whether an experimental drug, called SRD-001, is safe and helps the weakened heart of patients with Duchenne muscular dystrophy (DMD) regain its ability to effectively pump blood to the rest of the body. SRD-001 is a form of gene therapy. The goal of SRD-001 gene therapy is to provide the heart muscle cells with extra copies of the SERCA2a gene so that they can produce more SERCA2a protein to help the heart muscle cells squeeze/contract better. Researchers will compare SRD-001 treated participants with no-treatment participants; all participants will continue to take their current heart medications. All participants will be followed very closely for 2 years and undergo cardiac magnetic resonance imaging of their heart at baseline, year 1 and year 2 along with assessment of upper limb function and lung function. After the 2 years of close follow-up, all participants will roll over into long-term follow-up where they will be called biannually for information on their current medical status.

Will I have to stop taking my current medications?

No, you will not have to stop taking your current heart medications. The trial requires that all participants continue their existing heart treatments.

What safety data exists for SRD-001 or similar treatments for Duchenne Muscular Dystrophy?

Clinical trials for similar treatments, like NS-065/NCNP-01 and DT-DEC01, have shown favorable safety profiles with no severe adverse reactions reported. These studies suggest that such treatments are generally safe in humans, warranting further research. ^{1 2 3 4 5}

How does the drug SRD-001 differ from other treatments for Duchenne Muscular Dystrophy?

SRD-001 is unique because it likely involves antisense oligonucleotide (AON) therapy, which targets specific exons in the DMD gene to restore the production of a partially functional dystrophin protein. This approach is different from other treatments as it focuses on exon skipping to bypass mutations, potentially offering a more targeted and personalized treatment option for patients with specific genetic mutations. ^{1 2 6 7 8}

Research Team

Eligibility Criteria

This trial is for patients with Duchenne muscular dystrophy (DMD) who have a weakened heart. They must have confirmed DMD through genetic testing, specific signs of heart muscle damage, and reduced heart pumping function. Participants should be on stable heart medication and glucocorticoid treatment for at least one year.

Inclusion Criteria

I am willing and able to understand and give my consent for the trial.

My diagnosis of DMD is confirmed by genetic testing.

My heart has scarring in at least 3 areas.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a one-time intracoronary administration of SRD-001 or no intervention based on their neutralizing antibody status

1 day

1 visit (in-person, hospital stay overnight)

Follow-up

Participants are monitored for safety and effectiveness, including cardiac MRI and assessments of muscle and lung function

104 weeks

3 visits (in-person at baseline, year 1, and year 2)

Long-term follow-up

Participants will be called biannually for information on their current medical status

Indefinite

Treatment Details

Interventions

• SRD-001 (Gene Therapy)

Trial Overview The study tests SRD-001, an experimental gene therapy aimed to boost the SERCA2a protein in heart cells to improve their contraction ability. It compares treated participants against those without this new treatment while continuing standard medications over two years with additional long-term follow-up.

Participant Groups

Group I: Low Dose Experimental Treatment 1 Intervention

SRD-001

Group II: High Dose Experimental Treatment 1 Intervention

SRD-001

Group III: Control Active Control 1 Intervention

No-Intervention Control

Who Is Running the Clinical Trial?

Sardocor Corp.

Lead Sponsor

Trials

3

Recruited

80+

Findings from Research

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]

The DT-DEC01 cell therapy demonstrated a strong safety profile with no adverse events reported up to 21 months after administration, indicating it is a safe treatment option for patients with Duchenne Muscular Dystrophy (DMD).

Functional improvements were observed in patients, including better performance in the 6-Minute Walk Test and other assessments, suggesting that DT-DEC01 may effectively enhance muscle function and overall health in DMD patients over a 12-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration. Siemionow, M., Biegański, G., Niezgoda, A., et al.[2023]

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]

The del52hDMD/mdx mouse model allows researchers to effectively test human-specific antisense oligonucleotides (AONs) for Duchenne muscular dystrophy (DMD), enabling the study of exon skipping techniques that could restore functional dystrophin protein.

Using digital droplet PCR (ddPCR), researchers can accurately quantify exon skipping levels in human DMD transcripts, providing a precise method to evaluate the efficacy of AON treatments in this model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exon 51 Skipping Quantification by Digital Droplet PCR in del52hDMD/mdx Mice. Hiller, M., Spitali, P., Datson, N., et al.[2019]

A new Taqman quantitative RT-PCR assay was developed to accurately measure exon skipping in patients with Duchenne muscular dystrophy (DMD), providing a standardized method to evaluate the effectiveness of antisense oligomers like eteplirsen.

The study found that the levels of dystrophin protein restoration in patients correlated well with the RNA levels of exon skipping, establishing a reliable way to assess treatment success in clinical trials for DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exon skipping quantification by quantitative reverse-transcription polymerase chain reaction in Duchenne muscular dystrophy patients treated with the antisense oligomer eteplirsen. Anthony, K., Feng, L., Arechavala-Gomeza, V., et al.[2021]

This study successfully demonstrated over 70% efficiency in targeted exon skipping of the human dystrophin gene in a transgenic mouse model of Duchenne Muscular Dystrophy (DMD), marking a significant advancement in antisense therapy for this condition.

The research established a reliable method combining in vitro and in vivo approaches to evaluate the efficacy of antisense oligomers (AOs), which could help in selecting effective drugs for future clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted skipping of human dystrophin exons in transgenic mouse model systemically for antisense drug development. Wu, B., Benrashid, E., Lu, P., et al.[2021]

References

1. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Splice modification to restore functional dystrophin synthesis in Duchenne muscular dystrophy. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Shorter Phosphorodiamidate Morpholino Splice-Switching Oligonucleotides May Increase Exon-Skipping Efficacy in DMD. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Exon-skipping therapy: a roadblock, detour, or bump in the road? [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Exon 51 Skipping Quantification by Digital Droplet PCR in del52hDMD/mdx Mice. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Exon skipping quantification by quantitative reverse-transcription polymerase chain reaction in Duchenne muscular dystrophy patients treated with the antisense oligomer eteplirsen. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Targeted skipping of human dystrophin exons in transgenic mouse model systemically for antisense drug development. [2021]