Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT06907875

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

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Notify Me

Key information

Conditions

Facioscapulohumeral Muscular Dystrophy Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Muscular Diseases Muscular Disorders, Atrophic Muscular Dystrophies Muscular Dystrophy, Facioscapulohumeral Musculoskeletal Diseases Nervous System Diseases Neuromuscular Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Royal Alfred Hospital, Sydney, New South Wales, Australia

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

EPI-321

Biological

EPI-321 IV Infusion

Primary outcomes

  1. 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.

Secondary outcomes

  1. Vector Copy Number

    Time frame: Baseline, 3 and 12 months

    Change in vector copy number (as measured by vg/dg) within skeletal muscle biopsies.

  2. EPI-321 Cargo Transcriptional Activity

    Time frame: Baseline, 3 and 12 months

    Change in EPI-321 cargo transcriptional activity within skeletal muscle biopsies.

  3. 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.

  4. 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.

Sponsors and collaborators

Lead sponsor

Epicrispr Biotechnologies, Inc.

Industry

Registry information

Official study title

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

Acronym: FSHD

Important dates

Study start
2025
Primary completion
2027
Study completion
2032
First posted
Apr 2, 2025
Registry last updated
Jul 20, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.