PBGENE-DMD one-time IV gene-editing therapy for boys with DMD mutations treatable by removing exons 45–55

A Phase 1/2a, Multi-center, Open-label Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of PBGENE-DMD in Participants With Duchenne Muscular Dystrophy (FUNCTION-DMD)

This trial will test a single IV dose of PBGENE-DMD in boys ages 2–7 whose Duchenne mutations can be corrected by excising exons 45–55 to see if it is safe and shows early benefit.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 2 Years to 7 Years
• Sex: Male
• Sponsor: Precision BioSciences, Inc. (industry)
• Locations: 1 site (Little Rock, Arkansas)
• Trial ID: NCT07429240 on ClinicalTrials.gov

What this trial studies

This Phase 1/2a open-label, multicenter trial gives a single IV dose of PBGENE-DMD with a short-term, multimodal immunomodulatory regimen to reduce immune reactions. Up to 18 male participants aged 2–7 with genetically confirmed DMD mutations fully contained between exons 45 and 55 will be enrolled. The design has two parts: an initial dose confirmation/safety phase (Part 1) followed by an expansion phase (Part 2), with motor-function testing required at baseline and during follow-up. Each participant will be followed for approximately 130 weeks to monitor safety, tolerability, and preliminary motor outcomes.

Who should consider this trial

Good fit: Ideal candidates are ambulatory boys aged 2–7 with molecularly confirmed DMD mutations wholly contained between exons 45 and 55 who meet the study's age-specific motor-function requirements and vaccination history.

Not a fit: Patients with DMD mutations outside exons 45–55, those who do not meet the walking or NSAA criteria, older/non-ambulatory individuals, or females/carriers are unlikely to receive benefit from this approach.

Why it matters

Potential benefit: If successful, PBGENE-DMD could provide a one-time, durable genetic correction for the largest molecular subset of DMD patients, potentially slowing or preventing progressive muscle weakness.

How similar studies have performed: Exon-excision and gene-editing approaches have shown promising preclinical results and some early-phase gene therapies for DMD have reported signals, but one-time genomic editing in humans remains largely novel and unproven.

Eligibility criteria

Inclusion Criteria:

1. Males, 2 to 7 years of age, inclusive, at the time of informed consent/assent
2. Molecular confirmed DMD diagnosis (DMD mutation fully contained between exons 45 to 55 \[inclusive\])
3. Clinical phenotype consistent with DMD in the opinion of the Investigator
4. Ability to complete age-appropriate motor testing assessments requirements.

   Participants aged 2 to \< 4 years at the time of screening must:
   1. Be able to walk at least 10 meters independently (without assistive devices).
   2. Be able to rise from the floor without physical assistance (use of a Gowers' maneuver is acceptable).

      Participants aged 4 to 7 years at the time of screening must:
   3. Be able to walk at least 100 meters independently (without assistive devices).
   4. Have an NSAA total score between 16 and 29, inclusive.
5. Participant has received age-appropriate routine childhood immunizations per the local country's national immunization schedule.
6. The participant's parent(s)/LAR(s) are willing and able to provide written informed consent prior to the initiation of any trial-specific procedures; where applicable, the participant must provide written or verbal assent in accordance with local regulations.
7. The participant and their parent(s)/LAR(s) are willing to participate in a LTFU study after the completion of this trial.

Exclusion Criteria:

1. Prior treatment with any gene therapy, gene editing therapy, or cell-based therapy at any time.
2. Receipt of any investigational medication or experimental therapy within 6 months prior to Day 1.
3. Prior or ongoing use of any product designed to increase dystrophin expression, investigational, or otherwise, including exon-skipping therapies, within 6 months of the scheduled Day 1 dose or inability or unwillingness to refrain from initiating or resuming these therapies for at least 5 years following gene therapy administration.
4. Prior ongoing use of any product designed to increase dystrophin expression, investigational, or otherwise, including exon-skipping therapies, within 6 months of the scheduled Day 1 dose.
5. Concurrent enrollment in another clinical trial, unless it is observational (non-interventional).
6. A positive test for antibodies to AAV9
7. A participant has any condition that would contraindicate treatment with immunosuppression.
8. Participants with pathogenic mutations in exons 1-44 and/or exons 56-79.
9. Evidence of cardiomyopathy or clinically significant left ventricular dysfunction, defined as LVEF \<50% on screening echocardiogram.

Where this trial is running

Little Rock, Arkansas

• Arkansas Children's Hospital — Little Rock, Arkansas, United States (RECRUITING)

Study contacts

• Study coordinator: Precision BioSciences Clin Ops

Conditions: Duchenne Muscular Dystrophy With Mutations Amenable to PBGENE-DMD, Duchenne muscular dystrophy, DMD, X-linked Muscle wasting disease, Muscular dystrophy, Progressive muscle weakness, Gene editing, AAV serotype 9