A Phase 1/2 interventional study of EPI-321 in Facioscapulohumeral Muscular Dystrophy, sponsored by Epicrispr Biotechnologies, Inc.. Active, not recruiting at 7 sites in 3 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-08-19.
Sponsored by Epicrispr Biotechnologies, Inc. · Phase 1/2, Interventional, and Treatment
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.
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.
74 studies on the registry are indexed under Muscular Dystrophy, Facioscapulohumeral; 25 are open to participants now.
This study's planned enrollment of 12 is below the median of 30 across 45 interventional studies indexed under Muscular Dystrophy, Facioscapulohumeral.
Browse Muscular Dystrophy, Facioscapulohumeral studies →This is the only study on the registry with Epicrispr Biotechnologies, Inc. as lead sponsor.
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Exclusion Criteria:
Single IV infusion of a target dose of 2x10\^13 vg/kg
Biological: EPI-321
Single IV infusion of a target dose of 4x10\^13 vg/kg
Biological: EPI-321
EPI-321 IV Infusion
Frequency of AEs and EPI-321 Related Adverse Reactions and Serious Adverse Reactions
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.
Time frame: Baseline to up to 5 years.
Vector Copy Number
Change in vector copy number (as measured by vg/dg) within skeletal muscle biopsies.
Time frame: Baseline, 3 and 12 months
EPI-321 Cargo Transcriptional Activity
Change in EPI-321 cargo transcriptional activity within skeletal muscle biopsies.
Time frame: Baseline, 3 and 12 months
DUX4 Expression
Change in the expression of DUX4 and downstream markers (DUX4 Composite Score) within skeletal muscle biopsies.
Time frame: Baseline, 3 and 12 months
Methylation Status
Change from baseline in the methylation status of the 4q35 D4Z4 region within skeletal muscle biopsies at 3 and 12 months.
Time frame: Baseline, 3 and 12 months
Plan to share: No
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This study is active, not recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Muscular Dystrophy, Facioscapulohumeral→