Clinical trial NCT06821529: Stereotactic Intracerebral Injection of IPSC-DAPs in Patients with Parkinson's Disease
Official title: Stereotactic Intracerebral Injection of Autologous Induced Pluripotent Stem Cell-derived Dopamine Progenitor Cells in Patients with Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Parkinson Disease
Lead sponsor: iCamuno Biotherapeutics Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Second Affiliated Hospital, School of Medicine, Zhejiang University
First posted: 2025-02-12
Enrollment: 12
Sex: ALL
Minimum age (years): 39
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Parkinson's disease is a progressive neurodegenerative disorder characterized by high morbidity due to the limited regenerative capacity of dopaminergic neurons in the brain. Current drug treatments primarily manage symptoms but do not halt or reverse neuronal loss. Cellular replacement therapy has emerged as a potential strategy to restore dopaminergic function and address the underlying neuronal deficits. This study aims to evaluate the safety, feasibility, and efficacy of transplanting dopaminergic neurons into the brain to improve motor function and quality of life in patients with advanced Parkinson's disease.

Detailed description: Patients with Parkinson's disease will be treated with autologous induced pluripotent stem cell-derived dopamine progenitor cells (iPSC-DAPs). These cells will be transplanted directly into the striatum to restore dopamine-producing capacity. Patients will be evaluated at 1, 3, 6, 9 and 12 months after transplantation for safety, feasibility, and efficacy.

Eligibility criteria: Inclusion Criteria:

* Able to sign informed consent and comply with the study protocol
* 39-75 years of age, at the time of signing informed consent
* Diagnosed to be Parkinson's disease patients over 5 years
* Taking levodopa, but with complications of therapy such as wearing off and/or dyskinesia
* At least 3 hours accumulative "off" time per day
* Hoehn and Yahr Stage 2.5 - 4 in the off state at screening
* Dopamine drug responsiveness demonstrated by a positive "on/off" test with at least a 30% improvement on UPDRS III (motor) scale

Exclusion Criteria:

* Patients with the following concomitant conditions or disorders: Epilepsy；Multiple sclerosis；Unable to give consent due to dementia；Atypical Parkinsonism；Genetic Parkinson's disease；Suicidal ideation associated with intent or plan in the past 12 months；History of psychosis；History of subarachnoid hemorrhage；History of stroke or transient ischemic attack
* Patient with unstable vital sign at screening and/or prior to the surgery:
* Estimated Glomerular Filtration Rate (eGFR) \< 60 ml/min/1.73m2
* Liver dysfunction, as evidenced by enzymes (AST and ALT) greater than three times the ULN.
* Hematologic abnormality: hemoglobin \<10 mg/dL or platelet count \< 100,000/mL
* International normalized ratio (INR) ≥ 1.3 not due to a reversible cause
* Patients with autoimmune disorders
* Patients with HIV and/or active HBV or HCV
* Patients who are unable to undergo MRI and PET/CT
* Patients with an expected life expectancy of \<1 year
* Patients who have had active malignancies
* Patients currently receive levodopa-carbidopa intestinal gel or apomorphine treatment
* Patients who have history of pallidotomy or thalamotomy or deep brain stimulation (DBS) surgery
* Received cell or gene therapy (autologous or allogeneic) within the previous 12 months
* Participation in an investigational therapeutic or device trial within 30 days of consent
* Women who are pregnant or breast-feeding
* Other conditions that researchers consider not suitable to participate in this study

Primary outcomes:
measure: Incidence and servility of Treatment-Emergent Adverse Events
timeFrame: From baseline to 12 months post surgery
Secondary outcomes:
measure: changes in motor function
timeFrame: From baseline to 12 months post surgery
measure: Changes in the Hoehn and Yahr scale
timeFrame: From baseline to 12 months post surgery
measure: Changes in quality of life (QoL)
timeFrame: From baseline to 12 months post surgery
measure: Change in PD medication usage
timeFrame: From baseline to 12 months post surgery
measure: 18-F DAT PET uptake
timeFrame: Baseline, 6 and 12 months post surgery
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The Second Affiliated Hospital Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Baorong Zhang
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: Gao Chen
role: PRINCIPAL_INVESTIGATOR
References: