SRD-001 for Duchenne Muscular Dystrophy

(MUSIC-DMD Trial)

Recruiting at 2 trial locations

Overseen By Sardocor Corp.

Age: 18+

Sex: Male

Trial Phase: Phase 1

Sponsor: Sardocor Corp.

Must be taking: Cardiac medications, Glucocorticoids

Disqualifiers: Abnormal blood pressure, Liver issues, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 1 day

12 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new gene therapy, SRD-001, for people with Duchenne muscular dystrophy (DMD). Researchers seek to determine if SRD-001 can improve heart muscle function by boosting a protein that aids in pumping blood. Participants will receive either a low or high dose of SRD-001 or no new treatment while continuing their current heart medications. The trial seeks individuals with DMD who have a weakened heart muscle affecting its ability to pump blood effectively. Participants will undergo close monitoring for two years with heart imaging and other health assessments. As a Phase 1 trial, this research focuses on understanding how SRD-001 works in people, offering participants the chance to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that SRD-001 is likely to be safe for humans?

Research shows that SRD-001, a type of gene therapy, is being tested to strengthen the hearts of patients with Duchenne muscular dystrophy (DMD). This treatment works by providing heart cells with extra copies of the SERCA2a gene to improve heart function.

Since SRD-001 is in the early testing phase, detailed safety information for humans is not yet available. Early trials are designed to assess a treatment's safety, typically involving a small number of participants and closely monitoring for side effects. If SRD-001 progresses to later testing stages, it indicates promising initial safety results.

SRD-001 is also under study for other heart conditions, suggesting some level of safety. However, different conditions and patients might react differently. Participants in this trial will be closely monitored to ensure their safety and to gather important information on how well the treatment is tolerated. ^{1 2 3 4 5}

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

Unlike the standard treatments for Duchenne Muscular Dystrophy, which typically include corticosteroids to slow muscle damage, SRD-001 operates through a different mechanism. Researchers are excited about SRD-001 because it is designed to enhance muscle repair and regeneration directly, potentially addressing the root cause of muscle deterioration. Additionally, it offers a novel delivery method that targets muscle cells more effectively, which could lead to better outcomes with fewer side effects. This innovative approach is why SRD-001 holds promise for significantly improving the lives of those affected by this condition.

What evidence suggests that SRD-001 might be an effective treatment for Duchenne muscular dystrophy?

Research shows that SRD-001 is designed to aid the heart in patients with Duchenne muscular dystrophy (DMD) by increasing a protein called SERCA2a. This protein helps heart muscle cells contract more effectively. Early studies suggest that boosting SERCA2a could enhance heart function by improving its ability to pump blood. Although human studies have provided limited data, the concept involves giving heart cells extra copies of the SERCA2a gene to potentially improve heart performance and ease some DMD symptoms. While SRD-001 remains in early testing stages, its mechanism appears promising. Participants in this trial will receive either a low dose or high dose of SRD-001, or join a no-intervention control group. ^{3 4 5 6 7}

Are You a Good Fit for This Trial?

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.

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 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

What Are the Treatments Tested in This Trial?

Interventions

• SRD-001

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

In a phase 1 clinical trial involving 10 patients with Duchenne muscular dystrophy (DMD), the morpholino antisense oligonucleotide NS-065/NCNP-01 was found to have a favorable safety profile, with no severe adverse reactions reported during the 12-week treatment period.

NS-065/NCNP-01 successfully induced exon 53 skipping in dystrophin mRNA in a dose-dependent manner, leading to increased dystrophin expression in 7 out of 10 patients, suggesting its potential efficacy and warranting further investigation in phase 2 trials.

NCBI (Pubmed)

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. Komaki, H., Nagata, T., Saito, T., et al.[2019]

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 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]

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]

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]

Induced exon skipping therapy for Duchenne muscular dystrophy (DMD) has advanced from laboratory testing to successful Phase I clinical trials in humans, demonstrating that antisense oligomers can effectively redirect dystrophin gene processing by excising specific exons, such as exon 51.

While initial results from systemic delivery of these therapies in DMD patients are promising, the approach is only applicable to about 10% of individuals with DMD, highlighting the need for improved delivery methods and the expansion of this therapy to target other mutations in the dystrophin gene.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Splice modification to restore functional dystrophin synthesis in Duchenne muscular dystrophy. Wilton, SD., Fletcher, S.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06224660?term=SERCA2a&viewType=Table&rank=7

Study Details | NCT06224660 | Modulation of SERCA2a ... 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 ( ...

2. nationwidechildrens.org nationwidechildrens.org/research/clinical-research/gene-therapy-clinical-research/srd-001-1004

Duchenne Muscular Dystrophy Study 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 ( ...

3. dmdwarrior.com dmdwarrior.com/medera-cardiomyopathy-gene-therapy-trial-srd-001-for-duchenne-muscular-dystrophy/

SRD-001 Cardiomyopathy Gene Therapy Trial for ... Capricor Therapeutics Announces Positive Data Demonstrating Long-Term Efficacy of Deramiocel for the Treatment of Duchenne Muscular Dystrophy.

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/453962

Modulation of SERCA2a of Intra-Myocytic Calcium ... 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 ...

5. trialx.com trialx.com/clinical-trials/listings/303894/modulation-of-serca2a-of-intra-myocytic-calcium-trafficking-in-cardiomyopathy-secondary-to-duchenne-muscular-dystrophy/?&geo_lat=38.9822282&geo_lng=-94.6707917&radius=10&place=Overland%20Park&user_country=United%20States

Modulation of SERCA2a of Intra-Myocytic Calcium ... This research study is testing whether an experimental drug, called SRD-001, is safe and helps the weakened heart of patients with Duchenne ...

6. convention.bio.org convention.bio.org/program-1/medera-inc

Medera Inc. We are also developing SRD-003 for Duchenne muscular dystrophy-associated cardiomyopathy and SRD-001 for heart failure with reduced ejection ...

7. withpower.com withpower.com/trial/phase-1-muscular-dystrophies-2-2024-42bba

SRD-001 for Duchenne Muscular Dystrophy 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 ...