NCT07085195

A Clinical Study of the Safety and Efficacy of Chemogenetics Therapy in the Treatment of Parkinson's Disease

• Status: Not Yet Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Sponsor: Ruijin Hospital · Academic / Other
• Sex: All
• Age: 40 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The investigators propose a gene therapy strategy using chemical genetic inhibition to intervene in the abnormal activity of the subthalamic nucleus in Parkinson's disease. The investigators design and construct a highly efficient therapeutic injection STP-001 (first drug), through the efficient adeno-associated virus capsid (AAV), neuronal promoter (hSyn), and chemical genetic effector element (hM4Di), and accurately inject the drug into the bilateral subthalamic nucleus, the core pathological nucleus of Parkinson's disease, through stereotactic technology. Combined with a very low dose of clozapine (the second drug), the abnormal activity of the subthalamic nucleus is precisely intervened to improve the core motor symptoms of Parkinson's disease.

Detailed description

This is a single-arm and open-label study design for initial safety assessment. 6 cases of patients with iPD will be recruited from the neurology department of Ruijin Hospital, Affiliated Shanghai Jiao Tong University, School of Medicine. After the informed consent is signed, six participants will be divided into three dose groups in the dose escalation principle to receive the STP-001 injection. The virus dose escalation principle is as follows: After the first sentinel subject receives 1×10¹² vg virus vectors, the research team will evaluate the safety, tolerability, and efficacy of the current drug dose after 4 weeks. If this sentinel does not experience dose-limiting toxicity, another sentinel subject will receive a 2×10¹² vg dose; if this sentinel develops dose-limiting toxicity (DLT), this dose will be defined as an intolerable dose, and the Data Review Committee will determine whether to select a lower dose for exploration or terminate dose escalation based on the existing data. If this sentinel subject doesn't experience dose-limiting toxicity, another subject will receive a 4×10¹² vg dose. If this sentinel subject doesn't experience DLT, all of the next three subjects will receive a 4×10¹² vg dose. 4 weeks After receiving the STP-001 injection, when the participants have recovered, clozapine ramp-up will be performed, and the participants will be treated orally with clozapine. Clozapine is 25 mg per tablet, and the oral dose is 1/32, 1/16, and 1/8 tablet twice a day, in the morning and at noon, respectively, with each dose repeated for 3 days for a total of 9 days. If no DLT develops during this time, the participants will continue to take 1/8 pill orally twice a day as a maintenance dose, and they will be monitored for 12 months.

Conditions

• Parkinson Disease (PD)
• Gene Therapy
• Safety and Efficacy
• Clozapine

Interventions

Type	Name	Description
GENETIC	gene therapy	Six participants are planned to be divided into three dose groups in the dose escalation principle. The dose escalation principle is as follows: After the first sentinel subject receives 1×10¹² vg virus vectors, the research team will evaluate the safety, tolerability, and efficacy of the current drug dose after 4 weeks. If this sentinel does not experience dose-limiting toxicity, another sentinel subject will receive a 2×10¹² vg dose; if this sentinel develops dose-limiting toxicity (DLT), this dose will be defined as an intolerable dose, and the Data Review Committee will determine whether to select a lower dose for exploration or terminate dose escalation based on the existing data. If this sentinel subject doesn't experience dose-limiting toxicity, another participant will receive a 4×10¹² vg dose as a new sentinel subject. If this sentinel subject doesn't experience DLT, all of the next three subjects will receive a 4×10¹² vg dose.
DRUG	clozapine	Clozapine ramp-up will be performed four weeks after neurosurgery, when the participants have recovered, and the participants will be treated orally with clozapine. Clozapine is 25mg per tablet, and the oral dose is 1/32, 1/16, and 1/8 tablet twice a day, in the morning and at noon, respectively, with each dose repeated for 3 days for a total of 9 days. If no DLT develops during this time, the participants will continue to take 1/8 pill orally twice a day as a maintenance dose, and they will be monitored for 12 months.

Timeline

• Start date: 2025-08-01
• Primary completion: 2025-12-30
• Completion: 2025-12-30
• First posted: 2025-07-25
• Last updated: 2025-07-25

Locations

1 site across 1 country: China