Developmental Delay Disorder, Intellectual Disability, Rare Diseases
Conditions
Brief summary
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
Interventions
GENETICDual 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.
Sponsors
Yongguo Yu
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 10 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of drug-related serious adverse events | 0-26 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the changes using the Clinical Global impression Scale -Overall improvement (CGI-I) | 0-26 weeks | 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. |
| Evaluate the changes in the Patient's Global Impressions of Improvement (PGI-I) scale | 0-26 weeks | 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. |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORYongguo Yu, Dr, MD, PhD
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
PRINCIPAL_INVESTIGATORZilong Qiu, PhD
Shanghai Jiao Tong University School of Medicine Songjiang Research Institute
Outcome results
None listed