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

Prior treatment

• The subject is anti-HTLV-1 antibody-positive.
• The subject has hypersensitivity or contraindication to tacrolimus, concomitant drugs (e.g., levodopa, carbidopa, MRI contrast), and/or their components.
• The subject has undergone transplantation of human iPSC-derived dopaminergic progenitors.

Other illness

• 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 been diagnosed with a major neurocognitive disorder such as dementia, or is high risk for this.
• 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 has active infection such as hepatitis C or syphilis (STS/TPHA).
• 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.

Lab values

• The subject has bleeding tendency or abnormal coagulation function as evidenced by platelets \<50 or PT/PTT \> 1.5x normal.
• The subject has any of the following conditions/diseases concurrently:
  • Active malignancy
  • 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

Other

• The subject has clinical indication or diagnosis of abnormal immune function.
• Contraindications to general anesthesia as evaluated by subject matter experts.
• The subject is pregnant or lactating or does not agree to avoid pregnancy throughout the study.
• The subject, in the opinion of the investigator or sub investigator, is not appropriate to conduct the study safely.

• 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.