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

Phase Ⅰ/Ⅱa Clinical Trial to Evaluate the Safety, Tolerability and Efficacy of Intravenous Injection of Human Umbilical Cord Mesenchymal Stem Cells (hUC-MSCs) in Patients With Premature Ovarian Insufficiency (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 <1000 copies/mL), and patients with cured HCV (negative HCV RNA test) may be enrolled if deemed eligible by the investigator;
5. Subjects receiving or planning to use the following medications during the trial: oral or systemic corticosteroids, danazol, anticoagulants, Chinese herbal medicines or botanical supplements that may affect hormone levels or ovarian function;
6. History of hypersensitivity to human serum albumin;
7. Pregnant or breastfeeding subjects;
8. Participation in another clinical trial within the past 3 months, or receipt of other cell therapies (excluding blood transfusion);
9. History of malignant tumors;
10. Subjects with contraindications or cautions for estrogen use, including known or suspected breast cancer, endometrial cancer, other known or suspected sex hormone-dependent malignancies, active venous or arterial thromboembolic diseases within the last 6 months, undiagnosed abnormal genital bleeding, severe hepatic or renal insufficiency [serum aspartate aminotransferase (AST) >3×ULN, serum alanine aminotransferase (ALT) >3×ULN, estimated glomerular filtration rate (eGFR) <60 mL/min], etc.;
11. Uncontrolled diabetes, hypertension (>150/100 mmHg), heart disease, etc.;
12. Any other conditions judged by the investigator to render the subject unsuitable for participation in this study.