Facioscapulohumeral Muscular Dystrophy
Conditions
Keywords
Facioscapulohumeral Muscular Dystrophy, EPI-321, Muscular Dystrophy
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.
Interventions
BIOLOGICALEPI-321
EPI-321 IV Infusion
Sponsors
Epicrispr Biotechnologies, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Dose escalation with two dose levels
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of AEs and EPI-321 Related Adverse Reactions and Serious Adverse Reactions | 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
| Measure | Time frame | Description |
|---|---|---|
| Vector Copy Number | Baseline, 3 and 12 months | Change in vector copy number (as measured by vg/dg) within skeletal muscle biopsies. |
| EPI-321 Cargo Transcriptional Activity | Baseline, 3 and 12 months | Change in EPI-321 cargo transcriptional activity within skeletal muscle biopsies. |
| DUX4 Expression | Baseline, 3 and 12 months | Change in the expression of DUX4 and downstream markers (DUX4 Composite Score) within skeletal muscle biopsies. |
| Methylation Status | 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. |
Countries
Australia, New Zealand, United States
Outcome results
None listed