A Phase 1 Study of NCR201 in Parkinson's Disease Patients With Prior DBS

Prior treatment

• Subjects with persistent active infection, cerebrospinal fluid leak, or unhealed wounds in the previous brain surgical area; malfunction of implanted devices, electrode displacement, or other conditions judged by the investigator to pose significant risks to the subject or interfere with study assessments; subjects who are unable to safely complete protocol-specified MRI examinations under the conditions specified in the DBS system instructions and study site SOP (including but not limited to device/lead combinations that do not meet scanning requirements or other MRI contraindications); subjects with any contraindication to surgery or anesthesia as assessed by the investigator; or subjects with other prior surgical conditions deemed by the investigator to interfere with study participation.
• Head CT/MRI demonstrating brain trauma, cerebrovascular malformation, hydrocephalus, brain tumor, basal ganglia cerebral infarction lesions or other brain injuries, severe cerebral atrophy, or imaging abnormalities in the striatum or other brain regions that substantially increase surgical risk.
• Subjects with active disseminated intravascular coagulation and obvious bleeding tendency within 3 months prior to signing the informed consent form, or subjects who cannot discontinue antiplatelet agents or other anticoagulant agents for at least 5 days prior to surgery.
• Subjects with alcohol addiction, or positive drug abuse screening test.
• Subjects with severe dyskinesia in the medication ON state.

Other illness

• Subjects with any of the following: positive human immunodeficiency virus (HIV) antibody; positive Treponema pallidum antibody; positive hepatitis C virus (HCV) antibody with HCV RNA copy number greater than the lower limit of the assay normal range; positive hepatitis B virus (HBV) surface antigen with HBV DNA copy number greater than the lower limit of the assay normal range; active tuberculosis; or other active infections judged by the investigator that may interfere with subject participation or study outcomes.
• Subjects with dementia or severe cognitive impairment at screening.
• Subjects with a significant history of psychiatric disorders at screening, or suffering from severe depression.
• Subjects who have participated in clinical trials of stem cell therapy or gene therapy for Parkinson's disease.
• History of severe allergy or hypersensitivity reactions.
• Other conditions that, in the investigator's opinion, would render the subject unsuitable for this clinical study.

Other

• Atypical or secondary Parkinsonism.
• Lactating women; female subjects with pregnancy or oocyte donation plans from study initiation through the follow-up period; male subjects (or their partners) with fertility or sperm donation plans from study initiation through the follow-up period and refuse to take contraceptive measures.

• Aged between 26 and 70 years (inclusive), male or female.
• Diagnosed with primary Parkinson's disease (consistent with Chinese Parkinson's Disease Diagnostic Criteria, 2016 version). The subject has previously undergone intracranial deep brain stimulation (DBS) implantation surgery, with disease duration ≥ 5 years.
• Modified Hoehn-Yahr stage 3-4 (inclusive) in the DBS ON and medication OFF state.
• MDS-UPDRS Part III score ≥30 in the DBS ON and medication OFF state; a positive Madopar challenge test (improvement rate of MDS-UPDRS Part III score ≥30%), and on a stable anti-Parkinsonian medication.