A Phase I/II Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of Human Allogeneic Induced Pluripotent Stem Cell-derived Dopaminergic Neural Progenitor Cell Injection in the Treatment of Early-onset Parkinson's Disease
This study is a Phase I/II clinical study to evaluate the safety, tolerability, and efficacy of XS411 in the treatment of EOPD. The study consists of two phases: Phase I and Phase II. Phase I study is planned to be conducted in patients with EOPD, using a single-arm, open-label, traditional 3+3 dose-escalation design, aiming to investigate the safety, tolerability and preliminary efficacy of XS411 in the treatment of EOPD and to determine the RP2D. Phase I study enrolls 6-12 patients with EOPD. Two dose cohorts (3-6 patients/dose cohort) are planned: 9×10⁶ cells /patient and 1.8 ×10⁷ cells /patient. Each participant will receive a single injection of XS411. Each participant in each dose cohort will be observed for at least 28 days after dosing . If no DLTs occur and the investigator has no other safety concerns for that participant, the next participant in that dose cohort will be enrolled. Phase II study is planned for patients with EOPD, using a randomized, double-blind, sham-controlled, parallel-group design . The study will investigate the efficacy and safety of XS411 in the treatment of EOPD . Phase II study currently plans to enroll 81 patients with EOPD. The patients will be randomly assigned in a 2:1 ratio to either the experimental or control group. Participants in the experimental group will receive a single injection of XS411 in combination with an immunosuppressant at the RP2D determined during the Phase I dose-escalation phase (which may be adjusted based on the Phase II study results). The control group will receive a sham procedure in combination with an immunosuppressant sham.
• 18 years old ≤ age of onset ≤ 50 years old, diagnosed with EOPD (meeting the MDS 2015 clinical diagnostic criteria for Parkinson's disease );
• 18 years old ≤ age at enrollment ≤ 70 years old , male/female;
• Disease duration ≥ 5 years;
• Phase I: the modified Hoehn-Yahr grade in the off-phase is 3-4 (including the critical value) , and the modified Hoehn-Yahr grade in the on-phase is ≤3 ; Phase II: the modified Hoehn-Yahr grade in the off-phase is 2-4 (including the critical value) , and the modified Hoehn-Yahr grade in the on-phase is ≤3;
• Off-period MDS -UPDRS-III score \>30;
• Positive L-dopa stress test;
• The patient is unable to adequately control motor fluctuations even with a stable dose of medication recommended in the Guidelines for the Treatment of Parkinson's Disease in China (Fourth Edition) ;
• Patients received stable doses of anti-PD drugs for at least 4 weeks before administration;
• Able to accept surgical anesthesia, suitable for neurosurgery under anesthesia, and able to undergo brain CT /MRI examination;
• Participants agree to postpone any other elective neurosurgery until the completion of the 24-month follow-up study;
• Participants agreed not to participate in any other clinical studies within 24 months after dosing;
• Participants or their legal representatives understand and comply with the research procedures, voluntarily participate and sign the ICF