Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation

Safety, Tolerability and Preliminary Efficacy Study of a Single Intrathecal Injection of the Dual Vector AAV-CHD3-R1025W Base Editor for the Treatment of Developmental Disorders Caused by the R1025W Mutation in the CHD3 Gene

To evaluate the safety, tolerability and preliminary efficacy study of a single intrathecal injection of the dual vector AAV-CHD3-R1025W base editor for the treatment of developmental disorders caused by the R1025W mutation in the CHD3 gene

Study Overview

• Status: Recruiting
• Conditions: Intellectual Disability; Rare Diseases; Developmental Delay Disorder
• Intervention / Treatment: Genetic: Dual vector DNA base editor

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

Contacts and Locations

• Study Contact: Name: Xiaomei Luo, Ms., Master; Phone Number: +86-25-25076466; Email: luoxiaomei@shsmu.edu.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Recruiting
      • Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      • Contact: Xiaomei Luo, Master; Phone Number: +86-21-25076466; Email: luoxiaomei@shsmu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Clinical diagnosis of Snijders Blok-Campeau syndrome
• Heterozygous mutation of c.3073C>T, p.(Arg1025Trp) in the CHD3 gene
• Normal liver, heart and immune function
• Normal coagulation and platelet counts

Exclusion Criteria:

• Brain tumor or intracranial space-occupying lesion
• Contraindications to administration of lumbar puncture or sheath injection administration
• Persistent status epilepticus or recurrent epileptic control instability
• Presence of unstable systemic disease including active bacterial, fungal or HIV, hepatitis A, hepatitis B infection
• Serum anti-AAV neutralizing antibody titer >1:50 (ELISA immunoassay)
• Treatment with immunological agents other than protocol-specified prophylaxis within 3 months
• Prior gene therapy
• Participation in another clinical trial, or treatment with another investigational product within 30 days or 5 half-lives
• Known allergy to any investigational product

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: Dual vector treatment group

Genetic: Dual vector DNA base editor; The base editor is delivered using a dual vector adeno-associated virus (AAV) system and introduced into the child via intrathecal injection to correct the mutated CHD3 gene. The vital signs of the child will be closely monitored during treatment to assess possible acute adverse effects. The child will be followed up regularly after treatment to monitor the success of gene editing and the neurodevelopmental improvement of the child. Possible long-term adverse events will be closely monitored to assess the safety of the treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of drug-related serious adverse events	0-26 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the changes using the Clinical Global impression Scale -Overall improvement (CGI-I)	This 7-point scale (1 = very much improved, 7 = very much worse, etc.) is used by the clinician to assess the participant's overall performance status; higher scores indicate increased severity.	0-26 weeks
Evaluate the changes in the Patient's Global Impressions of Improvement (PGI-I) scale	This 7-point scale (1 = very much improved, 7 = very much worse, etc.) is used by the clinician to assess the participant's overall performance status; higher scores indicate increased severity.	0-26 weeks

Collaborators and Investigators

• Sponsor: Yongguo Yu
• Investigators: Principal Investigator: Yongguo Yu, Dr, MD, PhD, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine; Principal Investigator: Zilong Qiu, PhD, Shanghai Jiao Tong University School of Medicine Songjiang Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2025
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: February 24, 2025
• First Submitted That Met QC Criteria: March 5, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 5, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Pathologic Processes; Disease Attributes; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Developmental Disabilities; Rare Diseases; Intellectual Disability
• Other Study ID Numbers: XH-25-002

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