VGN-Ex05e in Patients With Autism Spectrum Disorder Associated With Severe Self-Injurious and Aggressive Behaviors

Official title

An Early-Phase Clinical Study to Evaluate the Tolerability, Safety, and Efficacy of VGN-Ex05e in Patients With Autism Spectrum Disorder (ASD) Associated With Severe, Treatment-Resistant Self-Injurious and Aggressive Behaviors

Overview

To evaluate the safety and tolerability of intracerebral injection of VGN-Ex05e in the nucleus accumbens of patients with autism spectrum disorder.

Detailed description

This study is a single-center, open-label, Investigator-Initiated Trial. The entire trial is expected to enroll 6 subjects. The initial plan of this study is to explore two doses: 2.0×10\^6 cells and 6.0×10\^6 cells. During the trial, the SRC (Safety Review Committee) will conduct a comprehensive assessment and may adjust the dose as necessary.

Interventions

• Biological VGN-Ex05e
  Products derived from human embryonic stem cells for the treatment of allogeneic nerve cells

Primary outcome measures

• Incidence and severity of adverse events [Time frame: through study completion, an average of 1 year]

Secondary outcome measures (5)

• change of Repetitive Behavior Scale-Revised score [Time frame: through study completion, an average of 1 year]
• change of Childhood Autism Rating Scale score [Time frame: through study completion, an average of 1 year]
• change of Autism Diagnostic Observation Schedule-Second Edition score [Time frame: through study completion, an average of 1 year]
• change of Aberrant Behavior Checklist score [Time frame: through study completion, an average of 1 year]
• change of Behavior Problems Index score [Time frame: through study completion, an average of 1 year]

Eligibility criteria

Inclusion criteria

• Male or Female, age >7, ≤18
• DSM-5 diagnosis of Autism Spectrum Disorder, confirmed by ADOS-2
• Diagnosis ≥ 2 years, with at least 6 months of unsuccessful systematic behavioral interventions or training, or those unable to undergo training;
• Target symptoms and severity: Presence of recurrent self-injurious or aggressive behaviors within the last 3 months, with at least one of the following documented (meeting at least one criterion): Any self-injury item on the RBS-R scoring ≥ 3; Self-injury/aggression subscale of the BPI reaching one of the following criteria: frequency score ≥ 3, or severity score ≥ 3;
• Previous use of multiple medications (one or more antipsychotics and one or more mood stabilizers) with inadequate response, or those with severe adverse reactions, or those who cannot tolerate，and have discontinued medication for more than 5 half-lives or 1 month (whichever is longer) prior to screening, with the expectation that these medications will not be re-administered during the study period;
• Subjects/parents/guardians are able to understand the trial information, objectives, and risks as described in the informed consent form, are willing to comply with the clinical trial protocol, and can authorize the use of the subject's health information, voluntarily providing the signed and dated informed consent form;
• Subjects/parents/guardians are willing to act as information providers for the study, providing information on the subject's health status, cognitive, and physical abilities (including providing information for scales).
• Male and female subjects of childbearing potential must continuously and correctly use at least one highly effective method of contraception from the screening period through at least 1 year after administration.

Exclusion criteria

• Refractory epilepsy within the last 12 months prior to screening (≥2 seizures per month or status epilepticus), or significant EEG discharges during the screening period with a high-risk assessment;
• Co-occurring schizophrenia, bipolar disorder, or severe depressive disorder;
• Severe cardiac, hepatic, renal, or hematologic diseases;
• Coagulation disorders or bleeding tendencies (affecting surgical drug administration);
• Active infection at the time of screening, requiring systemic treatment;
• Co-occurring malignant tumors or history of tumors within the past 5 years；
• Positive HIV antibody, active hepatitis C infection, active hepatitis B infection, syphilis positive, or active tuberculosis at the time of screening;
• clinically significant abnormal ECG;
• Any of the following laboratory test indicators meet the following criteria (those who meet the criteria and have a clear reason for retesting can recheck and confirm within one week): 1) Hemoglobin count is below the detection limit, or thrombocytopenia (< 100 × 10\^9/L); 2) Alanine aminotransferase ≥ 3 × ULN and/or Aspartate aminotransferase ≥ 3 × ULN and/or Total bilirubin ≥ 2 × ULN; 3) Those with renal function impairment, defined as eGFR < 60 ml/min/1.73 m2; 4) Myocardial enzyme spectrum (Creatine kinase CK and Creatine kinase isoenzyme CK-MB) > 3 × ULN; 5) Any laboratory abnormal value with significant clinical significance that other researchers consider may interfere with the efficacy and safety data analysis of this study.
• previous history of stem cell therapy or gene therapy;
• pregnant or lactating.
• Any history of intracranial infection or traumatic brain injury within 6 months prior to screening.
• MRI evidence of space-occupying lesions, arteriovenous malformations, active intracranial hemorrhage or infarction, diffuse cerebral atrophy, or severe developmental malformations.
• Prior intracranial surgical scarring that interferes with the planned trajectory to the nucleus accumbens (NAc).
• Participation in another clinical trial within 3 months prior to screening.
• History of severe hypersensitivity or allergic reactions to anesthetic agents or any components of the cell product.
• Presence of cranial metallic materials or implanted devices that contraindicate MRI, cause significant imaging artifacts affecting surgical navigation, or other conditions that preclude MRI examination.
• Any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in the clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07433517 · VGN-Ex05e-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗