Evaluation of the Safety, Tolerability, and Efficacy of LE051 in Patients With Duchenne Muscular Dystrophy

Evaluation of the Safety, Tolerability, and Efficacy of a Single Intravenous Injection of LE051 in Patients With Duchenne Muscular Dystrophy (DMD)

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.

Study Overview

• Status: Recruiting
• Conditions: Duchenne Muscular Dystrophy (DMD)
• Intervention / Treatment: Drug: LE051

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Jiwen Wang; Phone Number: +86 189 1661 3192; Email: wangjiwen@scmc.com.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200127
      • Recruiting
      • Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine
      • Contact: Jiwen Wang; Phone Number: +86 189 1661 3192; Email: wangjiwen@scmc.com.cn
      • Contact: Jiwen Wang

Participation Criteria

Eligibility Criteria

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

Description

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.

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: LE051 treatment; Single dose intravenous injection of LE051	Drug: LE051; LE051 dose escalation : dose 1 and dose 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Frequency of AEs, SAEs	from day 1 to week 52 after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in 6-Minute Walk Distance Compared to Baseline		from day 1 to week 52 after treatment
Changes in Supine-to-Stand Time Compared to Baseline		from day 1 to week 52 after treatment
Changes in 4-Stair Climb Time Compared to Baseline		from day 1 to week 52 after treatment
Changes in 10-Meter Walk/Run Time Compared to Baseline		from day 1 to week 52 after treatment
Changes in Dystrophin Protein Expression Levels in Muscle Tissue Compared to Baseline		from day 1 to week 52 after treatment
Changes in the Percentage of Dystrophin-Positive Muscle Fibers Compared to Baseline		from day 1 to week 52 after treatment
Changes in North Star Ambulatory Assessment (NSAA) Scores Compared to Baseline	The North Star Ambulatory Assessment (NSAA) comprises 17 items yielding a total score between 0 and 34 points, with increased scores correlating with improved motor performance.	from day 1 to week 52 after treatment

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 24, 2024
• Primary Completion (Estimated): September 20, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 23, 2025
• First Submitted That Met QC Criteria: March 23, 2025
• First Posted (Actual): March 28, 2025

Study Record Updates

• Last Update Posted (Actual): April 2, 2025
• Last Update Submitted That Met QC Criteria: March 28, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Duchenne Muscular Dystrophy
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Muscular Disorders, Atrophic; Muscular Dystrophies; Muscular Dystrophy, Duchenne
• Other Study ID Numbers: LE051-1

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: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No