Safety and Feasibility of Bilateral Striatal Transplantation of DopaCell in Parkinson's Disease

Official title

Evaluation of the Safety and Feasibility of a Single Transplantation of 10 Million Human Embryonic Stem Cell-Derived Dopaminergic Progenitor Cells Into the Bilateral Striatum of Patients With Moderately Severe Parkinson's Disease: a Multicenter, Open-label, Single-arm Phase I Clinical Trial

Overview

Dopason is a phase I, open-label, multicenter, single-arm clinical trial designed to evaluate the safety and feasibility of intraputaminal transplantation of human embryonic stem cell-derived dopaminergic progenitor cells (DopaCells) in patients with moderately severe Parkinson's disease.

Detailed description

During this trial phase, a total of six participants will be included and distributed between two clinical centers. Each participant will undergo one standardized surgical procedure consisting of bilateral stereotactic intraputaminal transplantation of approximately 10 × 10⁶ cells in total (about 5 × 10⁶ cells per putamen), aiming to achieve an estimated survival of 200,000 neurons. All procedures will be performed using the same surgical delivery system and an almost identical operative protocol across both sites to ensure procedural consistency. After transplantation, patients will receive immunosuppressive therapy for a duration of one year and will be systematically followed for study outcomes for at least 12 months.

Interventions

• Biological Dopacell
  DopaCells are dopamine-producing progenitor cells generated from human embryonic stem cells through differentiation under GMP-compliant conditions.
• Drug Immunosuppressive Regimen
  Basiliximab, Tacrolimus, Prednisolone
• Device Customized microinjection device
  For intraputaminal delivery of DopaCell

Primary outcome measures

• Safety [Time frame: Baseline to 12 Months Post-Transplant]
• Safety [Time frame: Baseline to 12 Months Post-Transplant]
• Feasibility [Time frame: Baseline to 12 Months Post-Transplant]

Secondary outcome measures (4)

• Efficacy [Time frame: Baseline to 12 Months Post-Transplant]
• Efficacy [Time frame: Baseline to 12 Months Post-Transplant]
• Efficacy [Time frame: Baseline to 12 Months Post-Transplant]
• Continuous Safety [Time frame: Baseline to 60 Months Post-Transplant]

Eligibility criteria

Inclusion criteria

• Age: 30-70 years
• Diagnosis of PD: MDS clinical Diagnostic Criteria for Parkinson's disease
• The disease duration more than 5 years
• Moderate Parkinson's disease, defined as a Hoehn and Yahr stage of 2 or 3 during the OFF period.
• The patient is receiving oral pharmacological therapy, and in the opinion of the Principal Investigator, the patient's symptoms remain inadequately controlled despite optimal medical management, or the patient is experiencing adverse effects related to their current treatment
• No history or only mild levodopa-induced dyskinesia, defined as a score of 2 or less on the UDysRS scale in any body region during the ON state.
• The patient demonstrates a clinically meaningful response to a therapeutic dose of levodopa, as determined by the Principal Clinical Investigator or a trained specialist under the supervision of the Principal Investigator.
• The performance of different organs based on laboratory evaluations:

• Number of neutrophils ≥2000 / microliter
• Platelet count ≥100,000 / microliter
• AST / ALT: less than or equal to three times the maximum normal value at the intervention site
• Total bilirubin less than or equal to 1.5 times the maximum normal amount at the intervention site
• eGFR \* rate: greater than or equal to 60 ml / min / 1.73 m2 \* eGFR (mL / min / 1.73 m2) = 194 X Cr \^ -1.094 X age \^ -0.287 (X 0.739 for females)
• Informed consent

Exclusion criteria

• The abnormal function of immune system
• The symptomatic brain injuries (brain atrophy, cerebral Infarct, trauma, vascular malformation) confirmed by brain MRI
• Markedly reduced or normal signal in the ventral striatum on TRO-DaT SPECT imaging.
• Any abnormal findings on brain MRI.
• Positive GBA mutation test.
• Diagnosis of dementia based on a MoCA score < 24.
• The abnormality of thrombotic system or high risk of bleeding
• Positive for any of the following viral markers or active infections: HBsAg, HBsAb, HBcAb, anti-HIV antibodies, anti-HTLV-1\&2 antibodies, active hepatitis C infection, syphilis, or active CMV, VZV, EBV, or COVID-19 infection.
• Impossibility of MRI imaging for patients with metal in the body, pacemaker in the body, claustrophobia, with artificial heart valves that are incompatible with MRI or body weight is not within the tolerable range for MRI.
• Patients with contraindications to the study drug: Tacrolimus, Prednisolone, Basiliximab, Cotrimoxazole, MRI contrast agent.
• Patients undergoing other cell transplants, including embryonic stem cell-derived dopaminergic progenitor cells.
• Patients with a history of PD at the same time and concurrent: Malignant neoplasm, epilepsy, cerebral hemorrhage or a positive history
• Psychiatric disorders confirmed by a psychiatrist, including major depression, bipolar disorder, or schizophrenia, that are uncontrolled or treatment resistant.
• Patients with intellectual disability who, in the judgment of a psychiatrist, are unable to fully comprehend the study requirements.
• History of pallidotomy, thalamotomy, or deep brain stimulation (DBS).
• Patients considered high-risk candidates for surgery, particularly neurosurgery or DBS implantation, due to significant cardiovascular, pulmonary, or other systemic comorbidities identified during preoperative evaluation.
• Patients who have a history of taking the following in the three months prior to enrollment: Immunosuppressant, antipsychotic drug, anticonvulsant drugs or anticoagulant therapy (if discontinuation or perioperative adjustment is not feasible), botulinum toxin (within 6 months), phenol injections, or other treatments for dystonia or muscle spasm
• History of Apomorphine use
• History of chronic alcohol use or illicit drug abuse.
• Patients who are pregnant, lactating, or people who did not avoid pregnancy during the study.
• Patients who, according to the researchers' opinions, are not suitable for safe study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Iran · 3 centers

• Shiraz University of Medical Sciences — Shiraz
• Iran University of Medical Sciences — Tehran
• Royan Institute — Tehran

Identifiers

NCT: NCT07572071 · 402000063

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗