A First-in-human Study of EPI-321 in Facioscapulohumeral Muscular Dystrophy (FSHD)

April 20, 2026 updated by: Epicrispr Biotechnologies, Inc.

A Phase 1/2 Open-label Dose-escalation Study to Evaluate the Safety, Tolerability, and Biological Activity of EPI-321, an AAVrh74-delivered Epigenetic Editing Therapy in Adult FSHD Patients

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

EPI-321 is an investigational drug product comprising a recombinant adeno-associated viral vector, serotype rh74 (AAVrh74), for the delivery of genetic material encoding an epigenetic editor designed to address the root case of FSHD. AAVrh74 has been shown to transduce human skeletal muscle efficiently in the clinical experience. EPI-321's transgene product, a non-cutting, nuclease-dead mini, clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein (dCasONYX) with fuse epigenetic modulators, is designed to selectively bind the D4Z4 repeat region via the accompanying guide RNA, methylate CpG groups within the region near the DUX4 gene on chromosome 4q35, and thus repress the expression of toxic DUX4 protein, ameliorating the downstream pathology that drives FSHD. As it is under a muscle-specific promoter, the dCasONYX-fused protein is expected to be preferentially and actively expressed in muscle tissue following a single intravenous (IV) dose.

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 trial of drug activity. Two dose levels will be evaluated. In addition, this study will collect secondary outcome data on muscle function, imaging characteristics, and other markers of disease activity at the baseline and throughout the study to assess their utility as measures of drug activity in a future clinical trial.

Study Type

Interventional

Enrollment (Estimated)

12

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
    • New South Wales
  • New Zealand
      • Auckland, New Zealand, 0622
        • Recruiting
        • Pacific Clinical Research Network
        • Contact:
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • Recruiting
        • David Geffen School of Medicine at University of California, Los Angeles
        • Principal Investigator:
          • Perry Shieh, MD, PhD
        • Contact:
    • Georgia
      • Atlanta, Georgia, United States, 303329
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Recruiting
        • Kennedy Krieger Institute, Center for Genetic Muscle Disorders
        • Contact:
        • Principal Investigator:
          • Doris G Leung, MD, PhD
    • Massachusetts
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • Utah Program for Inherited Neuromuscular Disorders - University of Utah
        • Principal Investigator:
          • Russell Butterfield, MD, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Able and willing to provide informed consent
  • Male or female 18 to 75 years of age
  • Clinical diagnosis of FSHD with genetic Type 1
  • FSHD Ricci clinical severity score 2 to 4 (on 5-point scale)
  • Has adequate liver function
  • Has adequate kidney function

Exclusion Criteria:

  • Has an anti-AAVrh74 total binding antibody titer > 1:400
  • Requires a walker or wheelchair for ambulation
  • Pregnant and/or breastfeeding at baseline or is planning to become pregnant during the first 12 months following EPI-321 administration
  • Has FSHD Type 2
  • Has a concurrent or past medical conditions could jeopardize the safety of the participant

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EPI-321 Cohort 1 Single IV Dose
Single IV infusion of a target dose of 2x10^13 vg/kg
Biological: EPI-321
EPI-321 IV Infusion
Experimental: EPI-321 Cohort 2 Single IV Dose
Single IV infusion of a target dose of 4x10^13 vg/kg
Biological: EPI-321
EPI-321 IV Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency of AEs and EPI-321 Related Adverse Reactions and Serious Adverse Reactions
Time Frame: Baseline to up to 5 years.
All AEs, regardless of assessed relatedness to EPI-321, will be collected from the time of informed consent signature until the end of study participation. The Investigator is responsible for assessing the severity of an AE according to the NCI-CTCAE version 5.0.
Baseline to up to 5 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vector Copy Number
Time Frame: Baseline, 3 and 12 months
Change in vector copy number (as measured by vg/dg) within skeletal muscle biopsies.
Baseline, 3 and 12 months
EPI-321 Cargo Transcriptional Activity
Time Frame: Baseline, 3 and 12 months
Change in EPI-321 cargo transcriptional activity within skeletal muscle biopsies.
Baseline, 3 and 12 months
DUX4 Expression
Time Frame: Baseline, 3 and 12 months
Change in the expression of DUX4 and downstream markers (DUX4 Composite Score) within skeletal muscle biopsies.
Baseline, 3 and 12 months
Methylation Status
Time Frame: Baseline, 3 and 12 months
Change from baseline in the methylation status of the 4q35 D4Z4 region within skeletal muscle biopsies at 3 and 12 months.
Baseline, 3 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Epicrispr Biotechnologies, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 8, 2025

Primary Completion (Estimated)

March 31, 2031

Study Completion (Estimated)

April 30, 2032

Study Registration Dates

First Submitted

March 26, 2025

First Submitted That Met QC Criteria

March 26, 2025

First Posted (Actual)

April 2, 2025

Study Record Updates

Last Update Posted (Actual)

April 22, 2026

Last Update Submitted That Met QC Criteria

April 20, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EPI-321-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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