Phase Ⅰ/Ⅱa Trial Evaluating Intravenous hUC-MSCs Injection for Safety, Tolerability and Efficacy in Patients With POI

A Phase I/IIa clinical study evaluating the safety, tolerability and efficacy of intravenously administered human umbilical cord mesenchymal stem cell (hUC-MSCs) injection in patients with premature ovarian insufficiency (POI). The primary objective of the Phase I dose-escalation stage is to assess the safety and tolerability of intravenous infusion of hUC-MSCs injection for the treatment of POI, and to determine the recommended phase II dose (RP2D) for the Phase IIa clinical trial. The primary objective of the Phase IIa dose-expansion stage is to evaluate the efficacy of intravenous infusion of hUC-MSCs injection in POI treatment, and to generate data to support pivotal/confirmatory clinical trials.

Inclusion Criteria: 1. Aged 18 to 40 years at the time of signing the informed consent form (exclusive of the boundary values); 2. Meet the diagnostic criteria specified in the Expert Consensus on Clinical Diagnosis and Treatment of Premature Ovarian Insufficiency (2023 Edition): oligomenorrhea (menstrual cycle longer than 35 days) or amenorrhea for more than 4 months, with basal serum follicle-stimulating hormone (FSH) \> 25 U/L (tested on Days 2-4 of the menstrual cycle or during amenorrhea, at least twice with an interval of ≥4 weeks); 3. Satisfy one of the following two criteria: 1. Total number of antral follicles (AFC) with a diameter of 2-10 mm in bilateral ovaries \< 5; 2. Serum anti-Müllerian hormone (AMH) ≤ 7.85 pmol/L (equivalent to 1.1 ng/mL); 4. Have received standardized hormone replacement therapy (HRT) at a stable dose for ≥3 months prior to drug administration with stable hormone levels, and maintain stable HRT per medical advice throughout the trial (within 24 weeks after enrollment); 5. Have no fertility requirements; 6. Agree to use effective contraceptive measures throughout the trial period (such as complete abstinence, condoms, cervical caps plus spermicides, intrauterine devices, etc.); 7. Negative serum β-hCG test result during the screening period (to rule out pregnancy); 8. Fully understand the trial information and sign the informed consent form. Exclusion Criteria: 1. Subjects with primary amenorrhea; 2. Subjects with thyroid disorders (hypothyroidism/hyperthyroidism or thyroid malignant tumors) or resistant ovary syndrome (ROS); 3. Subjects with abnormal female karyotypes (e.g., Turner syndrome, Fragile X syndrome); 4. Positive serology tests (HBV antibody, HCV antibody, HIV antibody, syphilis). Exceptions: HBV carriers, patients with stable HBV after drug treatment (HBV DNA titer ≤500 IU/mL or copies \3×ULN, serum alanine aminotransferase (ALT) \>3×ULN, estimated glomerular filtration rate (eGFR) \150/100 mmHg), heart disease, etc.; 12. Any other conditions judged by the investigator to render the subject unsuitable for participation in this study.