EPI-321 for Muscular Dystrophy

(FSHD Trial)

Recruiting at 3 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?

The goal of this clinical trial is to learn how safe and tolerable EPI-321 is and whether there may be early signs it is working in male or female adult (18 to 75 years) participants with facioscapulohumeral muscular dystrophy (FSHD) Type 1 condition. The main questions it aims to answer are: How safe is EPI-321 and how well can people handle it over time? How does EPI-321 interact with its target and does it show early signs of working? Participants will receive a single dose of EPI-321 through a vein while being closely watched in a hospital and visit the clinic regularly for tests and checkups for about 5 years after getting EPI-321.

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.

What safety data exists for EPI-321 (eteplirsen) in humans?

Eteplirsen, also known as EPI-321, has been evaluated for safety in clinical trials for Duchenne muscular dystrophy. In these studies, eteplirsen was generally well-tolerated, with no severe adverse reactions reported, indicating a favorable safety profile. ^{1 2 3 4 5}

How is the drug EPI-321 different from other treatments for muscular dystrophy?

EPI-321 is unique because it likely involves exon skipping, a process that helps produce a functional version of the dystrophin protein, which is missing in muscular dystrophy. This approach is similar to other exon-skipping drugs like PRO-051, but EPI-321 may target different exons or use a different delivery method, making it potentially beneficial for a different subset of patients. ^{6 7 8 9 10}

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 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]

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]

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 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 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]

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]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Eteplirsen in the treatment of Duchenne muscular dystrophy. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Next-Generation SINE Compound KPT-8602 Ameliorates Dystrophic Pathology in Zebrafish and Mouse Models of DMD. [2023]

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

Chemical and mechanistic toxicology evaluation of exon skipping phosphorodiamidate morpholino oligomers in mdx mice. [2016]

5. 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]

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

Systemic administration of PRO051 in Duchenne's muscular dystrophy. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Novel cationic carotenoid lipids as delivery vectors of antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy. [2021]

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

Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice. [2021]

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

Eteplirsen treatment for Duchenne muscular dystrophy: Exon skipping and dystrophin production. [2019]

10. England pubmed.ncbi.nlm.nih.gov

PRO-051, an antisense oligonucleotide for the potential treatment of Duchenne muscular dystrophy. [2022]