PBGENE-DMD Phase 1/2a Safety and Preliminary Efficacy Study in Duchenne Muscular Dystrophy (FUNCTION-DMD)
Purpose
The purpose of this Phase 1/2a trial is to evaluate the safety, tolerability, and preliminary efficacy of PBGENE-DMD in patients with DMD harboring mutations amenable to excision of exons 45-55. Given the limitations of existing therapeutic strategies, PBGENE-DMD represents a novel, innovative approach with the potential for a one-time, durable correction of the underlying genetic defect in the largest molecular subset of patients with DMD.
Condition
- Duchenne Muscular Dystrophy With Mutations Amenable to PBGENE-DMD
Eligibility
- Eligible Ages
- Between 2 Years and 7 Years
- Eligible Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- 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
- 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.
Study Design
- Phase
- Phase 1/Phase 2
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Intervention Model Description
- A single dose of PBGENE-DMD administered Intravenously (IV) following screening and pretreatment. Total duration of trial intervention for each participant: approximately 130 weeks
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
- Masking Description
- Open label
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Experimental- Part 1 (Initial Safety) & Part 2 (Expansion) cohort |
The trial is planned to enroll participants into 2 parts as follows: - Part 1 (Initial Safety) A total of up to 6 participants may be enrolled. - Part 2 (Expansion) Up to 12 participants |
|
Recruiting Locations
Little Rock, Arkansas 72202
St Louis, Missouri 63110
More Details
- Status
- Recruiting
- Sponsor
- Precision BioSciences, Inc.
Detailed Description
This is a Phase 1/2a, open-label, multicenter trial designed to evaluate the safety, tolerability, and primary efficacy of a single IV dose of PBGENE-DMD in male participants with DMD presenting with mutations that may be amenable to treatment with PBGENE-DMD. A structured, multimodal, short-term immunomodulatory regimen will be administered around the time of dosing to mitigate the risk of potential immune-mediated responses. The trial consists of two parts: Part 1 is to confirm a safe and well-tolerated single dose of PBGENE-DMD that may be further evaluated in Part 2 (expansion). A total of up to 18 participants may be enrolled in this trial. Total duration of trial participation for each participant: approximately 130 weeks.