Clinical trial NCT06778265: An Exploratory Clinical Study of UX-DA001 in Subjects With Idiopathic Parkinson's Disease
Official title: An Exploratory Clinical Study to Evaluate UX-DA001 Injection (Human Midbrain Dopaminergic Progenitor Cells Injection) in Subjects With Idiopathic Parkinson's Disease
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: PHASE1
Conditions: Parkinson Disease, Idiopathic
Keywords: Idiopathic Parkinson´s Disease
autologous iPSC derived mDAPs
Midbrain Dopaminergic Progenitors
Induced pluripotent stem cells
mDAPs
stem cells
iPSC derived product
Lead sponsor: Shanghai UniXell Biotechnology Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Ruijin Hospital
First posted: 2025-01-16
Enrollment: 12
Sex: ALL
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open-label, single-center, dose-escalation and dose-expansion
Primary purpose: TREATMENT

Brief summary: This clinical study is designed to explore the safety and tolerability of UX-DA001. It will also explore if UX-DA001 works to improve motor function in subjects with Parkinson's disease. UX-DA001 manufactured from participant's own cells will differentiate into mature dopaminergic neurons after being transplanted into the brain of the participant.

Detailed description: This study is an open-label, single-center, dose-escalation and dose-expansion exploratory clinical study to evaluate the safety, tolerability, and potential efficacy of UX-DA001 Injection at different dose levels implanted in subjects with idiopathic PD.

Each subject receives only one dose of UX-DA001 for implantation into the putamen bilaterally using stereotactic neurosurgery under general anesthesia. Safety and tolerability of UX-DA001 and its effect on Parkinson's disease symptoms are assessed for 2 years post-treatment.

Eligibility criteria: Inclusion Criteria:

1. The subjects or their legally acceptable representative understand and comply with the study procedures, agree to participate in the clinical trial, and sign the ICF;
2. Aged between 50-75 years old, male or female;
3. Subjects diagnosed with idiopathic PD, with a medical history of 5-15 years;
4. Having received standard anti-PD treatment and been given optimal anti-PD treatment under the guidance of the investigator, but the efficacy has significantly declined;
5. Good response to levodopa medications; the LCT shows that the maximum improvement rate of the UPDRS part III score exceeds 30%;
6. The modified H\&Y scale of clinical "OFF" period is ≥ Stage 3 and ≤ Stage 4;
7. Taking a stable dosage of anti-PD medications for at least 4 weeks;
8. Good physical condition or stable concomitant diseases;
9. With reliable caregivers who can cooperate to complete the assessment items,
10. Subjects with good compliance.

Exclusion Criteria:

1. PD Subjects in whom previous genetic testing has found a GBA gene mutation or PD Subjects whom the investigator considers unsuitable for participation in this clinical study due to other gene mutations;
2. Subjects with the atypical Parkinson's syndrome or secondary Parkinson's syndrome;
3. Subjects with HIV, HBV, HCV, treponema pallidum (TP) infection, or other active infections;
4. Subjects with HTLV, EBV, CMV infections that lead to blood samples unsuitable for the preparation of cell products;
5. Subjects with a known hereditary disorder,
6. Subjects with any history of malignancy,
7. Subjects with other serious systemic diseases or functional disorders
8. Accompanied by other serious central nervous system diseases or serious cognitive and mental disorders;
9. Subjects who are currently receiving or have previously received cell therapy or other medicine effecting safety and efficacy assessement;
10. Subjects whose prior head CT/MRI examinations indicate brain injury, or Subjects with imaging abnormalities in the striatum and other brain regions leading to a significant increase in surgical risk, or Subjects who have previously undergone brain surgery;
11. Subjects with clinically significant abnormal results in coagulation function, or Subjects who have been using anticoagulants for a long time and cannot discontinue use;
12. Subjects with a history of severe allergy or hypersensitivity reactions, or a known history of hypersensitivity, or a history of intolerance to the investigational cellular drug or its excipients;
13. Subjects who have undergone other surgeries within the past six months that the investigator deems may affect this trial, or Subjects who cannot tolerate general anesthesia or stereotactic surgery;
14. Subjects with contraindications to MRI and PET scans,
15. Subjects with a history of alcoholism or drug abuse,
16. Women during pregnancy or lactation,
17. Subjects who have participated in other interventional clinical trials or similar clinical trials within the past 3 months,
18. Subjects with other conditions that are not suitable for participation in the clinical study as judged by the investigator.

Primary outcomes:
measure: The incidence and and severity of adverse events (AEs) associated with surgery and/or investigational product
timeFrame: within 4 weeks post surgery
measure: The incidence and severity of AEs/serious adverse events (SAEs)
timeFrame: From baseline to 2 years post surgery
Secondary outcomes:
measure: 18F-FP-CIT uptake using positron emission tomography (PET)
timeFrame: From baseline to 2 years post surgery
measure: The situation of implantation and overgrowth of transplanted cells using cranial MRI
timeFrame: From baseline to 2 years post surgery
measure: Changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score, part III, from baseline.
timeFrame: From baseline to 2 years post surgery
measure: Changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) score, part II, from baseline.
timeFrame: From baseline to 2 years post surgery
measure: Changes in modified modified Hoehn-Yahr (H&Y) scale from baseline
timeFrame: From baseline to 2 years post surgery
measure: Changes in daily levodopa equivalent dose (LED) from baseline.
timeFrame: From baseline to 2 years post surgery
measure: Changes in the scores of non-motor symptom scales (NMSS) from baseline.
timeFrame: From baseline to 2 years post surgery
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Jun Liu, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: