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.
Study details:
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
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
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
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1PHASE2
Study ID
NCT06907875
Intervention or treatment
BIOLOGICAL: EPI-321
Conditions
- Facioscapulohumeral Muscular Dystrophy
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Research sites nearby
Closest Location:
Royal Alfred Hospital
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Royal Alfred Hospital
Sydney, New South Wales, Australia
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Who is running the clinical trial?
Epicrispr Biotechnologies, Inc.
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?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: EPI-321 Cohort 1 Single IV Dose
| Biological: EPI-321 |
EXPERIMENTAL: EPI-321 Cohort 2 Single IV Dose
| Biological: EPI-321 |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Baseline to up to 5 years. |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Vector Copy Number | Change in vector copy number (as measured by vg/dg) within skeletal muscle biopsies. | Baseline, 3 and 12 months |
| EPI-321 Cargo Transcriptional Activity | Change in EPI-321 cargo transcriptional activity within skeletal muscle biopsies. | Baseline, 3 and 12 months |
| DUX4 Expression | Change in the expression of DUX4 and downstream markers (DUX4 Composite Score) within skeletal muscle biopsies. | 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. | Baseline, 3 and 12 months |
References
Clinical Trials Gov: A First-in-human Study of EPI-321 in Facioscapulohumeral Muscular DystrophyOther trials to consider
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