Clinical trial NCT06900049: Evaluation of the Safety, Tolerability, and Efficacy of LE051 in Patients With Duchenne Muscular Dystrophy
Official title: Evaluation of the Safety, Tolerability, and Efficacy of a Single Intravenous Injection of LE051 in Patients With Duchenne Muscular Dystrophy (DMD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Duchenne Muscular Dystrophy (DMD)
Keywords: Duchenne Muscular Dystrophy
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2025-03-28
Enrollment: 12
Sex: MALE
Minimum age (years): 4
Maximum age (years): 8
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety, tolerability, and efficacy of LE051 intravenous therapy in DMD patients treated with exon 51 skipping therapy.

Detailed description: This is a single-arm, open-label study to evaluate the safety, tolerability, efficacy, pharmacokinetic, pharmacodynamic, and immune response of LE051 after a single intravenous infusion in DMD patients, as well as the long-term safety and efficacy.

Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder arising from mutations in the dystrophin gene, leading to muscle weakness, disability, and premature mortality. LE051, an investigational therapy, incorporates a ADAR recruiting RNA expression cassette targeting human exon 51 and is delivered via adeno-associated virus. By inducing exon 51 skipping, LE051 holds the potential to treat approximately 13% of DMD patients.

Eligibility criteria: Key Inclusion Criteria:

* Male，4-8 years old at the beginning of screening (including boundary values;
* DMD subjects with a clinical diagnosis of DMD referred to the Duchenne Clinical Practice Guidelines for Progressive Muscular Dystrophy (2020 edition) and whose genetic test results were confirmed to be applicable to exon skipping at No.51.
* The subjects and/or his guardian voluntary participate in this trial and can comprehend and sign ICF.

Key Exclusion Criteria:

* Clinical signs of heart failure: left ventricular ejection fraction (LVEF) \<40%；
* The average FVC percentage of the predicted value is less than 40%；
* 12 lead ECG QT interval (QTc) \>0.45 seconds.

Primary outcomes:
measure: Frequency of AEs, SAEs
timeFrame: from day 1 to week 52 after treatment
Secondary outcomes:
measure: Changes in North Star Ambulatory Assessment (NSAA) Scores Compared to Baseline
timeFrame: from day 1 to week 52 after treatment
measure: Changes in 6-Minute Walk Distance Compared to Baseline
timeFrame: from day 1 to week 52 after treatment
measure: Changes in Supine-to-Stand Time Compared to Baseline
timeFrame: from day 1 to week 52 after treatment
measure: Changes in 4-Stair Climb Time Compared to Baseline
timeFrame: from day 1 to week 52 after treatment
measure: Changes in 10-Meter Walk/Run Time Compared to Baseline
timeFrame: from day 1 to week 52 after treatment
measure: Changes in Dystrophin Protein Expression Levels in Muscle Tissue Compared to Baseline
timeFrame: from day 1 to week 52 after treatment
measure: Changes in the Percentage of Dystrophin-Positive Muscle Fibers Compared to Baseline
timeFrame: from day 1 to week 52 after treatment
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
References: