Transplantation of Human iPS Cell-derived Dopaminergic Progenitors (CT1-DAP001) for Parkinson's Disease (Phase I/II)

Single-center, open-label, uncontrolled. The primary objective of this study is to evaluate the safety of CT1-DAP001 in subjects with Parkinson's disease by determining the incidence and severity of adverse events, especially graft expansion, after transplantation into the corpus striatum. Other objectives are to evaluate the efficacy of CT1-DAP001 through the assessment of Parkinson's disease symptoms and clinical severity or progression.

Inclusion criteria

• The subject has a diagnosis of PD (clinically established or clinically probable) in accordance with the MDS Clinical Diagnostic Criteria for Parkinson's Disease (2015).
• The subject has an inadequate response to drug treatments.
• The subject is ≥ 40 years and ≤ 75 years of age at the time of informed consent.
• The subject has had PD for at least 5 years.
• The subject has both ON and OFF (as demonstrated by the MDS-UPDRS Part III and a symptom diary).
• The subject does not have a debilitating dyskinesia score greater than or equal to 3 on the MDS-UPDRS.
• The subject is in stage 2 or higher on the Hoehn and Yahr scale at OFF time.
• The subject is in stage 3 or lower on the Hoehn and Yahr scale at ON time.
• The subject has an L-dopa response of 30% or more without influence of antiparkinsonian drugs.
• The subject has the following organ functions as determined by laboratory tests at Screening visit:

• Neutrophil count ≥ 2,000/μL
• Platelet count ≥ 5.0 × 104/μL
• AST, ALT ≤ 3.0 × upper limit of normal
• Total bilirubin ≤ 1.5 × upper limit of normal
• eGFR ≥ 60 mL/min/1.73 m2 (As part of Creatinine testing, an estimated glomerular filtration rate (mL/min/1.73 m2)will be calculated based on the CKD-EPI 2021 equation)
• The subject is willing to avoid pregnancy using abstinence, highly effective means of birth control, surgical sterility, or menopause.
• The subject is willing to comply with the protocol-required assessments.
• The subject provides written informed consent to participate in the study. If the subject cannot sign due to physical constraints, verbal consent may be provided with signature of a Legally Authorized Representative.

Exclusion criteria

• The subject has an abnormal brain MRI suggestive of brain pathology other than Parkinson's disease.
• Atypical parkinsonism (Parkinsonism-Plus syndrome, secondary parkinsonism, hereditary parkinsonism).
• The subject has clinical indication or diagnosis of abnormal immune function.
• The subject has been diagnosed with a major neurocognitive disorder such as dementia, or is high risk for this.
• The subject has bleeding tendency or abnormal coagulation function as evidenced by platelets <50 or PT/PTT > 1.5x normal.
• The subject is HBs antigen-positive, or HBs antibody- or HBc antibody-positive with evidence of HBV-DNA.
• The subject is anti-HIV antibody positive.
• The subject is anti-HTLV-1 antibody-positive.
• The subject has active infection such as hepatitis C or syphilis (STS/TPHA).
• The subject has hypersensitivity or contraindication to tacrolimus, concomitant drugs (e.g., levodopa, carbidopa, MRI contrast), and/or their components.
• Contraindications to general anesthesia as evaluated by subject matter experts.
• The subject has a serious allergy to a component (e.g., gentamicin, component of bovine origin, or component of porcine origin) used in the preparation of the study product.
• The subject has any of the following conditions/diseases concurrently:

• Malignant neoplasm
• Epilepsy
• Psychiatric disease (e.g., uncontrolled anxiety or depression, bipolar disorder, schizophrenia)
• Diabetes mellitus with poorly controlled blood glucose (glycosylated hemoglobin > 9.0%, or fasting plasma glucose (FPG) ≥ 200 mg/dL (11.1 mmol/L).
• Other serious concurrent diseases (e.g., cerebrovascular disorder, heart disease, chronic respiratory disease, inadequately controlled hypertension) as determined by the investigator.
• The subject has a history of any of the following:

• Prior malignancy < 5 years prior to Screening. Patients who had prior malignancies within 5 years and in complete remission with expected survival of more than 5 years are not excluded
• Epilepsy
• Cerebral hemorrhage or stroke
• Psychiatric disease (e.g., uncontrolled anxiety or depression, bipolar disorder, schizophrenia)
• Congenital long QT syndrome
• Pallidotomy, thalamotomy, or Deep Brain Stimulation
• The subject is pregnant or lactating or does not agree to avoid pregnancy throughout the study.
• The subject has undergone transplantation of human iPSC-derived dopaminergic progenitors.
• The subject, in the opinion of the investigator or sub investigator, is not appropriate to conduct the study safely.