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;
Non-primary PD or Parkinson's superimposed syndromes ;
Patients are in the late stages of PD and are experiencing severe, disabling peak-dose dyskinesia or biphasic dyskinesia and/or unpredictable or widely fluctuating symptoms;
Have previously undergone neuronucleotomy, deep brain stimulation (DBS), striatal surgery, extrapyramidal surgery, stereotactic brain surgery, or other brain surgery; or who have undergone other surgical procedures that the investigator determined would affect participation in this study; or who have surgical contraindications
Patients currently receiving L-dopa intestinal instillation, apomorphine injection, or continuous daily infusion of anti-PD drugs;
Sequential
human allogeneic induced pluripotent stem cell (iPSC)-derived dopaminergic neural progenitor cell injection
Drug5.0×10\^7 cells/mL, injection, once, 12 months
To evaluate the safety and tolerability of XS411 cell injection in the treatment of EOPD 28 days after administration
To evaluate the safety and tolerability of XS411 cell injection in the treatment of EOPD through the incidence and severity of AEs/SAEs; the incidence of DLTs ; Vital signs, physical examination, 12-lead ECG, clinical laboratory tests, and head MRI. AEs occurring during the study will be graded according to CTCAE V5.0. DLT is defined as: (1) any CTCAE grade 3 or 4 AE related to the trial drug (including definitely related, probably related, and possibly related) occurring within 28 days of trial drug administration (such as grade 3 or 4 immune system diseases, infectious diseases, mental illnesses, kidney diseases, etc. related to the trial drug ); (2) Grade 2 AEs cannot be reduced to grade 1 or below within 14 days.
To check the change on parameters in MDS-UPDRS questionnaire on Day 28, M3, M6, M9 and M12 to evaluate preliminary efficacy of XS411 cell injection.
To evaluate the preliminary efficacy of XS411 cell injection in the treatment of EOPD through Changes from baseline in the scores of parts I, II, III, and IV of the MDS-UPDRS (individual scores, total score, and sum of scores II and III) after administration ;
Evaluation of the improvement of nigrostriatal dopamine transmitter system through PET-CT testing data change compared with baseline in M6 and M12 for 9 partipants
To evaluation of the improvement of nigrostriatal dopamine transmitter system after XS411 cell injection in the treatment of EOPD through 18F-DOPA uptake in the striatum as shown by brain PET-CT at 6 and 12 months after administration compared with baseline.
To check the change on parameters Hoehn-Yahr (modified) questionnaire on Day 28, M3, M6, M9 and M12 to evaluate preliminary efficacy of XS411 cell injection.
To evaluate the preliminary efficacy of XS411 cell injection in the treatment of EOPD through Change from baseline in the Hoehn-Yahr (modified) Parkinson's disease rating scale score after administration ;
To check the change on parameters on OFF and ON-period change recorded in patient's diary on Day 28, M3, M6, M9 and M12 to evaluate preliminary efficacy of XS411 cell injection.
To evaluate the preliminary efficacy of XS411 cell injection in the treatment of EOPD through Change from baseline in on-period without bothersome dyskinesia; Change from baseline in conscious off-period; Change from baseline in on-period without dyskinesia recorded in Patient's diary
Evaluation of the improvement of nigrostriatal dopamine transmitter system after XS411 cell injection in the treatment of EOPD
To evaluation of the improvement of nigrostriatal dopamine transmitter system after XS411 cell injection in the treatment of EOPD through PET-CT testing data change compared with baseline in M6 and M12 for 9 partipants in the striatum as shown by brain PET at 6 and 12 months after administration compared with baseline.
Click on the lead sponsor to view all of their trials.
