Facioscapulohumeral Muscular DystrophyPhase 1/2FSHDNCT06907875
A First-in-human Study of EPI-321 in Facioscapulohumeral Muscular Dystrophy
A Phase 1/2 study testing EPI-321 in people with Facioscapulohumeral Muscular Dystrophy, run by Epicrispr Biotechnologies, Inc. at 7 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Facioscapulohumeral Muscular Dystrophy
- What is being tested?
- EPI-321
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 7 sitesin 3 countries
- Study dates
- 8 May 2025to 30 Apr 2032
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
7 sites in 3 countries.
7 sites in 3 countries
United States5 sites
Rare Disease Research
Atlanta, Georgia, 303329
Kennedy Krieger Institute, Center for Genetic Muscle Disorders
Baltimore, Maryland, 21205
David Geffen School of Medicine at University of California, Los Angeles
Los Angeles, California, 90095
Utah Program for Inherited Neuromuscular Disorders - University of Utah
Salt Lake City, Utah, 84112
University of Massachusetts Chan Medical School
Worcester, Massachusetts, 01605
New Zealand1 site
Pacific Clinical Research Network
Auckland, New Zealand, 0622
About this study
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
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.
Read the 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.
- Conditions
- Facioscapulohumeral Muscular Dystrophy
- Being tested
- EPI-321
- Keywords
- Facioscapulohumeral Muscular Dystrophy, EPI-321, Muscular Dystrophy
- Medical subject headings
- Muscular Dystrophy, Facioscapulohumeral, Muscular Dystrophies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EPI-321Biological
EPI-321 IV Infusion
| Study group | Role | What they receive |
|---|---|---|
| EPI-321 Cohort 1 Single IV Dose | Experimental | Single IV infusion of a target dose of 2x10^13 vg/kg Receives: Biological: EPI-321 |
| EPI-321 Cohort 2 Single IV Dose | Experimental | Single IV infusion of a target dose of 4x10^13 vg/kg Receives: Biological: EPI-321 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline to up to 5 years.
Secondary outcomes (4)
Vector Copy Number
Change in vector copy number (as measured by vg/dg) within skeletal muscle biopsies.
Measured: Baseline, 3 and 12 months
EPI-321 Cargo Transcriptional Activity
Change in EPI-321 cargo transcriptional activity within skeletal muscle biopsies.
Measured: Baseline, 3 and 12 months
DUX4 Expression
Change in the expression of DUX4 and downstream markers (DUX4 Composite Score) within skeletal muscle biopsies.
Measured: 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.
Measured: Baseline, 3 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2025
- Study start8 May 2025
- Primary completion7 Jul 2027 (estimated)
- Study completion30 Apr 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Facioscapulohumeral Muscular DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Dose escalation with two dose levels
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Epicrispr Biotechnologies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06907875
- Sponsor's protocol ID
- EPI-321-02
- Acronym
- FSHD
- Status last verified
- Aug 2026
- First submitted
- 26 Mar 2025
- Last updated
- 19 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT06907875
- Acronym / sponsor ID
- FSHD / EPI-321-02
- Conditions
- Facioscapulohumeral Muscular Dystrophy
- Keywords
- Facioscapulohumeral Muscular Dystrophy, EPI-321, Muscular Dystrophy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Epicrispr Biotechnologies, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 May 2025 (actual)
- Primary completion
- 7 Jul 2027 (estimated)
- Study completion
- 30 Apr 2032 (estimated)
- First posted
- 2 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Dose escalation with two dose levels
| Arm | Type | Receives |
|---|---|---|
| EPI-321 Cohort 1 Single IV Dose | Experimental | Biological: EPI-321Single IV infusion of a target dose of 2x10^13 vg/kg |
| EPI-321 Cohort 2 Single IV Dose | Experimental | Biological: EPI-321Single IV infusion of a target dose of 4x10^13 vg/kg |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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 is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EPI-321EPI-321 IV Infusion | Biological | EPI-321 Cohort 1 Single IV Dose, EPI-321 Cohort 2 Single IV Dose |
Primary outcome
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.
4 secondary outcomes
Vector Copy Number
Time frame: Baseline, 3 and 12 months
EPI-321 Cargo Transcriptional Activity
Time frame: Baseline, 3 and 12 months
DUX4 Expression
Time frame: Baseline, 3 and 12 months
Methylation Status
Time frame: Baseline, 3 and 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
7 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing EPI-321 in people with Facioscapulohumeral Muscular Dystrophy, run by Epicrispr Biotechnologies, Inc. at 7 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 19 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States, Australia, New Zealand. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frequency of AEs and EPI-321 Related Adverse Reactions and Serious Adverse Reactions (time frame: Baseline to up to 5 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2026.