Overview
This clinical study is designed to explore the safety and tolerability of UX-DA003. It will also explore if UX-DA003 works to improve motor function in subjects with Parkinson's disease.
Description
This study is a single-arm, open-label, dose-escalation exploratory clinical trial aimed at evaluating the safety, tolerability, and preliminary efficacy of different doses of UX-DA003 injections for treating patients with Parkinson's disease. Eligible participants are mid-to-late stage PD patients who have shown significant decline in response after standard PD treatment and have not undergone DBS surgery.
The study planned two dose groups: a low-dose group receiving 3.6×10\^6 cells per side (6 patients) and a high-dose group receiving 5.4×10\^6 cells per side (6 patients). A total of 12 patients are planned to be enrolled, with each patient receiving only one dose of UX-DA003 for bilateral putamen cell transplantation.
A Safety Monitoring Committee (SMC) has been set up for the study, which can decide based on safety data whether to include additional patients after the sentinel cases, start enrollment in the next dose group, explore other dose levels, increase the number of patients in any dose group, or stop/modify the trial protocol.
Enrollment for each dose group proceeds from low to high. Each dose group includes sentinel cases, where the first patient is monitored for 4 weeks after cell transplantation. Only after the SMC reviews the safety data can subsequent patients receive cell transplantation.
Four weeks after the last patient in each dose group receives transplantation, the SMC will conduct an overall safety assessment for all patients and discuss the next steps.
The trial visit schedule includes a screening period (D-30 to D-15), baseline period (D-14 to D-1), surgery and post-op observation period (D0 to D28), follow-up period (M3 to M24), and long-term follow-up period (Y3 to Y5). Screening and baseline periods involve screening checks, baseline assessment, and pre-op examinations. Surgery takes place on D0, with hospitalization required the day before (D-1) and on post-op day 4. Patients return to the hospital on day 14 (D14) and day 28 (D28) for follow-up. Follow-up visits occur at 3, 6, 9, 12, 18, and 24 months to assess safety and efficacy. Patients completing the 24-month follow-up enter the long-term follow-up period, with annual visits up to 5 years post-surgery.
During the trial, patients are allowed to continue using regular anti-Parkinson medications at a stable dose to manage PD symptoms.
Eligibility
Inclusion Criteria:
- \- Aged between 30 and 75 years, regardless of gender
- Diagnosed with Parkinson's disease conforming to relevant clinical diagnostic standards with a medical history of 5-20 years
- Having received standard anti-PD treatment and been given optimal anti-PD treatment under the guidance of the investigator, but the efficacy has significantly declined
- Good response to levodopa medications, the levodopa challenge test (LCT) shows that the maximum improvement rate of the UPDRS-III score exceeds 30%
- The modified H\&Y staging (Off period) of ≥2.5 and ≤4, with total daily "off" time \>2 hours
- Stable dose of anti-Parkinson' disease drugs for at least 4 weeks prior to screening
- Good physical condition or stable concomitant diseases
Exclusion Criteria:
- The subjects with atypical Parkinson's syndrome or secondary Parkinson's syndrome
- Severe systemic diseases or functional impairments
- Evidence of active infection or chronic infection, which may pose a risk to the subject
- Severe concomitant central nervous system diseases or severe cognitive and psychiatric disorders
- Subjects with a history of brain injuries, cerebral vascular malformations, hydrocephalus, brain tumors, or other brain damages as shown by previous Head CT/MRI scans, or subjects with abnormal brain imaging in the striatum or other brain regions that significantly increase surgical risks
- Subjects who have participated in clinical trials for stem cell therapy or gene therapy for Parkinson's disease, or have participated in other interventional clinical trials within the last 3 months
- Subjects with a history of severe allergies or hypersensitivity reactions, known hypersensitivity to the investigational drug or its ancillary materials, or intolerance to them
- Pregnant or breastfeeding women
