Epilepsy is a neurological disorder caused by various factors, characterized by recurrent, episodic, and transient dysfunction of the central nervous system due to excessive discharge of brain neurons. The unpredictability, suddenness, and recurrence of epilepsy cause serious physical and mental harm to patients. Moreover, the intense fear of epileptic seizures, leading to high tension and a stron
Conditions
Interventions
Trial group:Intracranial AAV injection via CED system assisted by surgical robot
oral administration of clozapine.
Sponsors
Xuanwu Hospital Capital Medical University
Eligibility
Sex/Gender
All
Age
12 Years to 50 Years
Inclusion criteria
Inclusion criteria: 1. Age between 12 and 50 years; for subjects under 18 years of age, they must agree to comply with all protocol requirements, and both the subject and their parent(s) or legal guardian must provide informed consent on an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)/Human Research Ethics Committee (HREC)-approved Informed Consent Form (ICF) prior to any study-related procedures. 2. Patients have been diagnosed with temporal lobe epilepsy with unilateral hippocampal sclerosis through multidisciplinary discussion involving neurology, neurosurgery, and radiology departments, with seizure frequency of at least 2 episodes per month on average over the past 3 months. 3. Patients have undergone standardized treatment with two or more antiepileptic drugs for at least two years without effective seizure control. 4. The investigator judges that the patient’s condition has remained stable over the past three months with no significant changes under a constant antiepileptic drug regimen. 5. Patients have been stably taking their current antiepileptic drugs for at least three months prior to baseline and are expected not to change the type or dosage of current medication during the efficacy observation period of this trial. 6. Patients voluntarily participate in the trial and provide informed consent after full understanding; patients or their caregivers must have the ability to receive and make phone calls. At the time of informed consent signing, each study participant must have a caregiver aged at least 18 years. The caregiver must be a relative, partner, legally authorized representative, or an individual providing daily care and having a significant personal relationship with the participant. The caregiver must be capable of recognizing and observing the participant’s epileptic seizures. 7. Subject laboratory values must meet the following criteria: (1) White blood cell count and neutrophil count are within normal limits or the abnormalities are not clinically significant; (2) Platelet count (PLT) >= 75 × 10^9/L; (3) Hemoglobin (HGB) >= 100 g/L; (4) Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <= 2.5 × upper limit of normal (ULN); (5) Coagulation function: prothrombin time and activated partial thromboplastin time <= 1.5 × ULN; (6) Adeno-associated virus antibody titer <= 1:1200. 8. Sexually active male or female subjects must agree to use effective contraception from the time of informed consent signing until at least six months after discontinuation of clozapine (oral contraceptives are prohibited). According to the investigator’s judgment, participants must be deemed reliable and capable of adhering to the trial protocol (e.g., understanding and completing diary cards), visit schedule, and medication regimen.
Exclusion criteria
Exclusion criteria: 1. Accompanied by degenerative central nervous system disorders or malignant tumors; 2. Seizure intervals judged by the investigator to be excessively variable; 3. Patients with secondary epilepsy due to intracranial malignant tumors, neurodegenerative diseases, traumatic brain injury, cerebral hemorrhage or infarction, infectious diseases, cerebrovascular disease, or other organic lesions; 4. Accompanied by severe psychiatric disorders (e.g., severe depression, schizophrenia, etc.); 5. Patients with contraindications to treatment or surgery as determined by the investigator; 6. Subjects unable or unsuitable to undergo non-invasive or invasive assessments related to the trial; 7. History of prior intracranial surgical intervention (excluding minimally invasive procedures performed for diagnostic purposes such as stereotactic puncture, or minimally invasive treatments such as radiofrequency or laser ablation; patients with implanted vagus nerve stimulators or deep brain stimulators are eligible); 8. Patients with known contraindications to any drugs used during the trial (e.g., components of GA002 injection, clozapine or its other constituents, contrast agents, etc.); 9. Subjects who have previously received any gene or cell therapy; 10. Subjects who have participated in any other drug clinical trial within the past 3 months prior to signing the informed consent form (excluding non-interventional clinical trials); subjects who have participated in device trials may be considered for inclusion at the investigator’s discretion; 11. Patients with severe hepatic or renal disease, severe cardiac disease (including cardiomyopathy, heart failure, arrhythmias, ischemic heart disease, congenital heart disease), severe pulmonary dysfunction, hypotension, glaucoma, or other serious underlying conditions; 12. Patients with aplastic bone marrow; 13. Patients currently taking medications known to cause agranulocytosis or bone marrow suppression; 14. Patients with a history of clozapine-induced agranulocytosis or severe neutropenia; 15. Patients with positive human immunodeficiency virus (HIV) antibody or positive syphilis treponema antibody; 16. Severely obese patients with BMI >= 30 kg/m^2; 17. Patients with gastrointestinal diseases affecting drug absorption, metabolism, or excretion (e.g., Crohn’s disease, severe intestinal infections, ulcers, acute or chronic pancreatitis, paralytic ileus) or those with a history of major gastrointestinal surgery or dysphagia; 18. History of alcohol or drug abuse within the past two years; 19. Pregnant women or those who are breastfeeding, as confirmed by positive pregnancy test; 20. Any other condition that, in the investigator’s judgment, may interfere with the evaluation of efficacy or safety.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence and severity of central nervous system and systemic adverse events (AEs) / serious adverse events (SAEs); | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy endpoints (including the change in average weekly seizure frequency during the efficacy observation period compared to the baseline average weekly frequency; the percentage change in the number of epileptiform discharges on scalp EEG during the efficacy observation period compared to baseline, etc.);Immunogenicity endpoints;Pharmacokinetic (PK) parameters;Neurological function indicators; | — |
Countries
China
Contacts
Public ContactZhao Guoguang
Xuanwu Hospital Capital Medical University
Outcome results
None listed