EPI-321 for Muscular Dystrophy

(FSHD Trial)

Recruiting at 5 trial locations

Overseen By Weston Miller, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Epicrispr Biotechnologies, Inc.

Disqualifiers: Anti-AAVrh74 antibodies, Walker use, Pregnancy, FSHD Type 2, Body mass >90 kg, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

9 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called EPI-321 for individuals with facioscapulohumeral muscular dystrophy (FSHD) Type 1. The researchers aim to determine the safety of EPI-321 and assess its tolerability over time. Participants will receive a single dose of the treatment through an IV and will be closely monitored for any signs of effectiveness. This trial is for adults diagnosed with FSHD Type 1 who do not require a walker or wheelchair for mobility. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that EPI-321 is likely to be safe for humans?

Research has shown that EPI-321 was safe in earlier studies with non-human primates (NHPs), meaning it was well-tolerated and did not cause serious side effects in those animals. EPI-321 is being tested as a "one-and-done" gene therapy, aiming to treat facioscapulohumeral muscular dystrophy (FSHD) by permanently reducing a harmful protein called DUX4. This trial marks one of the first steps in testing EPI-321 in humans, focusing on its safety and tolerability. As the trial is in its early stages, researchers continue to collect detailed safety information in humans. ^{1 2 3 4 5}

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

Researchers are excited about EPI-321 for muscular dystrophy because it uses a novel gene therapy approach. Unlike current treatments that often focus on managing symptoms, EPI-321 aims to address the root cause by delivering a therapeutic gene directly to muscle cells through a single intravenous infusion. This gene therapy approach has two dosing regimens: one with a target dose of 2x10^13 vg/kg and another with 4x10^13 vg/kg, offering the potential for more personalized treatment options. By targeting the underlying genetic defect, EPI-321 has the potential to significantly improve muscle function and quality of life for those affected by muscular dystrophy.

What evidence suggests that EPI-321 might be an effective treatment for muscular dystrophy?

Research has shown that EPI-321 may help treat facioscapulohumeral muscular dystrophy (FSHD) by reactivating a gene that was nearly inactive, potentially improving muscle function. In studies, EPI-321 increased muscle cell survival by 55%, suggesting it might help maintain muscle health longer. This trial will test EPI-321 in two separate cohorts, each receiving a different single IV dose. Although this treatment remains in the early stages, these findings support its potential to address important issues in FSHD. ^{2 5 6 7 8}

Are You a Good Fit for This Trial?

Adults aged 18 to 75 with a clinical diagnosis of Type 1 facioscapulohumeral muscular dystrophy (FSHD) can join this trial. They must be able to consent, have a moderate severity score for their condition, and good liver and kidney function.

Inclusion Criteria

I am willing and able to agree to participate in the study.

My liver is working well.

My kidneys are working well.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single IV dose of EPI-321 and are closely monitored in a hospital setting

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with regular clinic visits for tests and checkups

5 years

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• EPI-321

Trial Overview The study is testing EPI-321's safety, tolerability, and preliminary effectiveness in FSHD patients. Participants will receive one dose via IV and undergo regular monitoring and checkups over approximately five years.

How Is the Trial Designed?

Group I: EPI-321 Cohort 2 Single IV Dose Experimental Treatment 1 Intervention

Single IV infusion of a target dose of 4x10\^13 vg/kg

Group II: EPI-321 Cohort 1 Single IV Dose Experimental Treatment 1 Intervention

Single IV infusion of a target dose of 2x10\^13 vg/kg

Who Is Running the Clinical Trial?

Epicrispr Biotechnologies, Inc.

Lead Sponsor

Published Research Related to This Trial

In a long-term study of patients with Duchenne muscular dystrophy (DMD) treated with eteplirsen, 100% of patients showed successful skipping of exon 51, confirming the drug's mechanism of action.

Eteplirsen treatment resulted in significant increases in dystrophin production, with an 11.6-fold increase in dystrophin content and a 7.4-fold increase in the percentage of dystrophin-positive fibers compared to untreated controls, indicating its potential efficacy in restoring dystrophin levels in muscle cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eteplirsen treatment for Duchenne muscular dystrophy: Exon skipping and dystrophin production. Charleston, JS., Schnell, FJ., Dworzak, J., et al.[2019]

Eteplirsen (Exondys 51) has received accelerated FDA approval as a treatment for Duchenne muscular dystrophy (DMD) by promoting dystrophin production through exon skipping, specifically targeting exon 51, which is relevant for about 14% of DMD patients.

The review highlights the pharmacological, efficacy, safety, and tolerability data from preclinical and clinical trials, while also addressing concerns regarding the drug's efficacy and its role as a potential therapeutic strategy for DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Eteplirsen in the treatment of Duchenne muscular dystrophy. Lim, KR., Maruyama, R., Yokota, T.[2022]

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]

In a phase 3 study involving 79 patients aged 7-16 with Duchenne muscular dystrophy, eteplirsen treatment for 96 weeks resulted in a significant increase in dystrophin production (7-fold) and exon skipping (18.7-fold), indicating its efficacy in addressing the underlying cause of the disease.

The study also demonstrated a favorable safety profile, with most adverse events being mild to moderate and unrelated to the treatment, while showing a notable slowing of disease progression compared to untreated controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial. McDonald, CM., Shieh, PB., Abdel-Hamid, HZ., et al.[2022]

KPT-8602 (eltanexor) has shown promise as an oral treatment for Duchenne muscular dystrophy (DMD) in pre-clinical models, improving muscle integrity and overall outcomes in both zebrafish and mouse models.

The treatment not only enhanced locomotor behavior and muscle histology in D2-mdx mice but also shifted the immune response towards a more anti-inflammatory profile, suggesting it could be a safer alternative to corticosteroids for managing DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next-Generation SINE Compound KPT-8602 Ameliorates Dystrophic Pathology in Zebrafish and Mouse Models of DMD. English, KG., Reid, AL., Samani, A., et al.[2023]

In a phase 1-2a study involving 12 patients with Duchenne's muscular dystrophy, the antisense oligonucleotide PRO051 was administered subcutaneously, showing dose-dependent efficacy in inducing exon-51 skipping and new dystrophin expression in muscle fibers.

After 12 weeks of treatment, patients demonstrated a modest improvement in walking distance, with an average increase of 35.2 meters on the 6-minute walk test, indicating potential clinical benefits alongside observed safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic administration of PRO051 in Duchenne's muscular dystrophy. Goemans, NM., Tulinius, M., van den Akker, JT., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06907875

NCT06907875 | A First-in-human Study of EPI-321 ... In addition, this study will collect secondary outcome data on muscle function, imaging characteristics, and other markers of disease activity at the baseline ...

2. crisprmedicinenews.com crisprmedicinenews.com/clinical-trial/facioscapulohumeral-muscular-dystrophy-nct06907875/

Facioscapulohumeral Muscular Dystrophy, (NCT06907875) EPI-321-02 clinical trial is an open label dose ascending study of EPI-321 for safety and tolerability to determine the best dose for a future ...

3. epicrispr.com epicrispr.com/epicrispr-biotechnologies-presents-data-on-powerful-gene-reactivation-with-gems-epigenetic-editors-at-esgct/

Epicrispr Biotechnologies Presents Data on Powerful Gene ... Epicrispr's data demonstrate that the new modulator can reactivate a silenced gene to near 100% expression, with durability of more than 75 days.

4. cgtlive.com cgtlive.com/view/evaluating-epigenetic-gene-therapy-treatment-fshd

Evaluating Epigenetic Gene Therapy for the Treatment of ... Epic Bio is currently developing EPI-321, an investigational epigenetic gene therapy product intended to treat facioscapulohumeral muscular dystrophy (FSHD).

5. mdaconference.org mdaconference.org/abstract-library/epi-321-a-potential-cure-for-fshd/

EPI-321, a Potential Cure for FSHD In this model, EPI-321 resulted in a phenotypic rescue with 55% increased survival of skeletal muscle cells. Taken together, these data support the development ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0960896624005479

640P Efficacy and safety of EPI-321, an investigational ... Our findings provide robust evidence for EPI-321 as a “one-and-done” gene therapy for treating FSHD by permanently suppressing DUX4.

7. epicrispr.com epicrispr.com/epic-bio-presents-compelling-preclinical-data-supporting-clinical-initiation-of-epi-321-for-fshd/

Epicrispr Biotechnologies Presents Compelling Preclinical ... NHP studies demonstrate EPI-321's favorable safety and pharmacokinetic profile. IND and CTA applications planned for 2023.

8. fshdsociety.org fshdsociety.org/2025/08/06/epicrispr-8-6-25/

Epicrispr Biotechnologies Doses First Patient in ... The company's global first-in-human trial is evaluating the safety, tolerability, and pharmacodynamics of EPI-321 in adults with genetically ...