PBGENE-DMD Phase 1/2a Safety and Preliminary Efficacy Study in Duchenne Muscular Dystrophy (FUNCTION-DMD)

Prior treatment

• Prior treatment with any gene therapy, gene editing therapy, or cell-based therapy at any time.
• Receipt of any investigational medication or experimental therapy within 6 months prior to Day 1.
• 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.
• 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.
• Concurrent enrollment in another clinical trial, unless it is observational (non-interventional).
• A positive test for antibodies to AAV9
• A participant has any condition that would contraindicate treatment with immunosuppression.

Lab values

• Evidence of cardiomyopathy or clinically significant left ventricular dysfunction, defined as LVEF \<50% on screening echocardiogram.

Other

• Participants with pathogenic mutations in exons 1-44 and/or exons 56-79.

• Males, 2 to 7 years of age, inclusive, at the time of informed consent/assent
• Molecular confirmed DMD diagnosis (DMD mutation fully contained between exons 45 to 55 \[inclusive\])
• Clinical phenotype consistent with DMD in the opinion of the Investigator
• Ability to complete age-appropriate motor testing assessments requirements.
  • Participants aged 2 to \< 4 years at the time of screening must:
  • Be able to walk at least 10 meters independently (without assistive devices).
  • 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:
  • Be able to walk at least 100 meters independently (without assistive devices).
  • Have an NSAA total score between 16 and 29, inclusive.
• Participant has received age-appropriate routine childhood immunizations per the local country's national immunization schedule.
• 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.
• The participant and their parent(s)/LAR(s) are willing to participate in a LTFU study after the completion of this trial.