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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy With Mutations Amenable to PBGENE-DMD
• Intervention / Treatment: Biological: PBGENE-DMD (IV)

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.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Precision BioSciences Clin Ops; Phone Number: (800) 593-0346; Email: function-DMD@precisionbiosciences.com

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72202
      • Recruiting
      • Arkansas Children's Hospital
      • Principal Investigator: Aravindhan Veerapandiyan, MD
      • Contact: Kristin MacLean; Phone Number: 501-364-2079; Email: MacleanKD@archildrens.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	Biological: PBGENE-DMD (IV); Participants will receive a single dose of PBGENE-DMD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, severity, and causality of treatment-emergent adverse events and serious adverse events	Adverse events and serious adverse events that occur or worsen after initiation of the investigational treatment	From Dosing through Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dystrophin expression in skeletal muscle	Measurement of Biologic activity of PBGENE-DMD through dystrophin expression in skeletal muscle	Week 12, Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Developmental Motor Function 1	Change from baseline in the digital mobility outcome (DMO) of Stride Velocity 95th Centile (SV95C)	Week 52, Week 104
Developmental Motor Function 2	Change from baseline in Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-4) Motor Gross Motor and Fine Motor scores (<3 years of age)	Week 52, Week 104
Developmental Motor Function 3	Change from baseline (defined as the first assessment after the participant has reached 3 years of age) in North Star Ambulatory Assessment (NSAA) total score (≥ 3 years of age)	Week 52, Week 104
Developmental Motor Function 4	Change from baseline in participants ≥ 3 years of age in timed performance in 4-stair climb, time to rise (TTR), 10-meter walk/run (10MWR), 100-meter walk/run (only age >/= 4 years of age)	Week 52, Week 104

Collaborators and Investigators

• Sponsor: Precision BioSciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2026
• Primary Completion (Estimated): November 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: February 17, 2026
• First Submitted That Met QC Criteria: February 17, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: DMD; Duchenne muscular dystrophy; Muscular dystrophy; Gene editing; X-linked Muscle wasting disease; Progressive muscle weakness; AAV serotype 9; AAV-9; Exon 45-55 excision
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: PBGENE-DMD-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No