Primary Ovarian Insufficiency (Poi)
Conditions
Keywords
Primary Ovarian Insufficiency, MSC
Brief summary
The goal of this clinical trial is to evaluate the safety, tolerability and efficacy of human umbilical cord mesenchymal stem cell injection (HS\_SW01 cells injection) in patients with Primary Ovarian Insufficiency (POI). Participants will be required to sign the informed consent form and will only be assigned to the study and enrolled after undergoing a series of tests and meeting the inclusion and exclusion criteria of the protocol.
Detailed description
The goal of this clinical trial is to evaluate the safety, tolerability and efficacy of human umbilical cord mesenchymal stem cell injection (HS\_SW01 cells injection) in patients with Primary Ovarian Insufficiency (POI). Participants will be required to sign the informed consent form and will only be assigned to the study and enrolled after undergoing a series of tests and meeting the inclusion and exclusion criteria of the protocol. This trial consists of a Phase I dose-escalation stage and a Phase II dose-expansion stage. Phase I is a randomized, double-blind, placebo-controlled design in which all participants receive background therapy plus a single intravenous infusion of HS\_SW01 cells injection (1.0×10\^6 cells/kg, 2.0×10\^6 cells/kg, 3.0×10\^6 cells/kg) or placebo, with 4-7 participants per dose group. A "3+3" dose-escalation design is used to evaluate safety, tolerability, pharmacokinetics, and immunogenicity across the three dose groups. In Phase II, the optimal biological dose (OBD) identified from the Phase I escalation study will serve as the recommended Phase II dose (RP2D) to preliminarily assess efficacy while continuing safety monitoring, providing a basis for subsequent clinical trials. Eligible participants are patients with POI aged ≥18 to \<40 years who meet all inclusion criteria and none of the exclusion criteria.
Interventions
A single dose of 1×10\^6 cells/kg of HS\_SW01 cells injection will be given by intravenous infusion.
Sponsors
Shenzhen Huishan Biotechnology Co., Ltd.
Southern Medical University, China
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily sign the informed consent form; 2. Age ≥18 to \<40 years, with oligomenorrhea or amenorrhea \>4 months; 3. Serum baseline FSH \>25 U/L (at least two measurements, interval \>4 weeks); 4. Have received stable standard treatment for POI, such as ≥3 months of standardized hormone replacement therapy (HRT) with stable hormone levels; 5. No fertility requirement and adherence to strict contraception.
Exclusion criteria
1. Individuals with childbearing plans or those who are pregnant. 2. Genetic disorders, chromosomal abnormalities, or genetic defects known to cause premature ovarian insufficiency (POI). 3. Endocrine disorders affecting ovarian function, including polycystic ovary syndrome, hyperprolactinemia, hyperandrogenism, diabetes mellitus, and abnormalities of thyroid or adrenal function. 4. Presence of breast, uterine, or ovarian tumors; known or suspected sex hormone-dependent malignancies; or any other benign or malignant tumors. 5. Primary amenorrhea. 6. Uterine malformations. 7. Iatrogenic or drug-induced ovarian insufficiency. 8. Uncontrolled acute or chronic gynecological inflammation (including endometritis, etc.). 9. Bilateral endometrial thickness ≤8 mm after moderate-to-severe intrauterine adhesion surgery. 10. Complicated with endometriosis. 11. Severe functional impairment of major organs or coagulation disorders. 12. Active venous or arterial thromboembolic disease within the past 6 months. 13. Severe hepatic or renal insufficiency, etc. 14. Vaccination with live or live-attenuated vaccines within 2 months prior to enrollment. 15. Prior treatment with mesenchymal stem cells less than 3 months before enrollment. 16. Uncontrolled hypertension (\>150/100 mmHg). 17. Any of the following conditions within 3 months prior to enrollment: 1. Major trauma or major surgery (including joint surgery), or anticipated need for major surgery during the study period, which in the investigator's opinion poses unacceptable risk to the participant; 2. Receipt of plasma exchange or extracorporeal photopheresis; 3. Participation in any other interventional clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The incidence of DLT | Within 28 Days | Incidence of dose-limiting toxicities (DLTs) within 28 days following study drug administration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes of the Anti-Müllerian hormone (AMH) serum level from baseline. | Baseline, Week 4, Week 12, Week 24 | Evaluate the AMH serum level by blood sampling at baseline and at Week 4, Week 12 and Week 24 after administration to assess changes of the Anti-Müllerian hormone (AMH) serum level from baseline. |
| Changes of the Follicle Stimulating Hormone (FSH) serum level from baseline. | Baseline, Week 4, Week 12, Week 24 | Evaluate the FSH serum level by blood sampling at baseline and at Week 4, Week 12 and Week 24 after administration to assess changes of the Follicle Stimulating Hormone (FSH) serum level from baseline. |
| Changes of Luteinizing Hormone (LH) serum level from baseline. | Baseline, Week 4, Week 12, Week 24 | Evaluate the LH serum level by blood sampling at baseline and at Week 4, Week 12 and Week 24 after administration to assess changes of Luteinizing Hormone (LH) serum level from baseline. |
| Changes of the Estradiol (E2) serum level from baseline. | Baseline, Week 4, Week 12, Week 24 | Evaluate the E2 serum level by blood sampling at baseline and at Week 4, Week 12 and Week 24 after administration to assess changes of the Estradiol (E2) serum level from baseline. |
| Changes of the Antral Follicle Counting (AFC) from baseline. | Baseline, Week 4, Week 12, Week 24 | Evaluate the Antral Follicle Counting (AFC) by sonography at baseline and at Week 4, Week 12 and Week 24 after administration to assess Changes of the Antral Follicle Counting (AFC) from baseline . |
| Changes of the Ovarian Volume (OV) from baseline. | Baseline, Week 4, Week 12, Week 24 | Evaluate the Ovarian Volume (OV) by sonography at baseline and at Week 4, Week 12 and Week 24 after administration to assess Changes of the Ovarian Volume (OV) from baseline. |
| Changes of the menstrual function indicators from baseline. | Up to Week 24 | Menstrual function indicators will be recorded via patient diaries or visit questionnaires to evaluate the recovery of menstruation following treatment. The form includes the date of menstrual onset, duration of menstruation (in days), menstrual regularity (regular/irregular; regular defined as cycle fluctuation ≤7 days), and associated symptoms (dysmenorrhea/other, with descriptive notes).Menstrual blood loss will be assessed using the Pictorial Blood Loss Assessment Chart (PBAC), which records, for each menstrual cycle, the type and number of sanitary products used daily, the frequency of clots passed into the toilet, and the total menstrual blood loss (in mL). Menstrual function recovery is defined as meeting all of the following criteria: （1）At least two consecutive cycles of menstrual bleeding after treatment discontinuation;（2）Cycle length restored to 21-35 days;（3）Menstrual blood volume returned to pre-illness levels compared with the subject's own baseline. |
Outcome results
None listed