Clinical trial NCT06907875: A First-in-human Study of EPI-321 in Facioscapulohumeral Muscular Dystrophy
Official 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Facioscapulohumeral Muscular Dystrophy
Keywords: Facioscapulohumeral Muscular Dystrophy
EPI-321
Muscular Dystrophy
Lead sponsor: Epicrispr Biotechnologies, Inc.
Sponsor class: INDUSTRY
First posted: 2025-04-02
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation with two dose levels
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Frequency of AEs and EPI-321 Related Adverse Reactions and Serious Adverse Reactions
timeFrame: Baseline to up to 5 years.
Secondary outcomes:
measure: Vector Copy Number
timeFrame: Baseline, 3 and 12 months
measure: EPI-321 Cargo Transcriptional Activity
timeFrame: Baseline, 3 and 12 months
measure: DUX4 Expression
timeFrame: Baseline, 3 and 12 months
measure: Methylation Status
timeFrame: Baseline, 3 and 12 months
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Auckland
country: New Zealand
facility: Pacific Clinical Research Network
Study officials:
References: