A Proof of Concept Study to Evaluate Exosomes From Human Mesenchymal Stem Cells in Women With Premature Ovarian Insufficiency (POI)

VL-POI-01

The VL-POI-01 study is designed to evaluate the safety and efficacy of human placental mesenchymal stem cell derived exosome treatment in patients with premature ovarian insufficiency (POI) and diminished ovarian reserve.

2023-10-06

2025-10-01

2025-12-01

Recruiting

Early phase I

9

Inclusion Criteria: * Able to understand and communicate in English language * Female of age 18-43 years * Diagnosis of premature ovarian insufficiency based on ESHRE Guidelines (i) oligo/amenorrhea for at least 4 months, and (ii) an elevated FSH level \>25 IU/L on two occasions \>4 weeks apart, or diagnosis of low ovarian reserve defined as: Basal FSH value \>10 IU/L or failure of prior attempts of assisted reproductive techniques due to limited ovarian response (poor responders) * Normal karyotype 46, XX, and no known history FMR1 premutation (fragile X syndrome) * Baseline AMH levels ≤ 1.0 ng/mL * Presence of at least one ovary * Normal uterine anatomy (by any clinically and/or imaging acceptable methods) * Normal thyroid function as evident by normal serum Thyroid Stimulating Hormone (TSH) levels * For subjects who had contraception before, the duration of amenorrhea should be more than 3 months after discontinuation of the oral contraception pill (OCP) or more than 6 months after discontinuation of Depo Provera (or similar) therapies * Agree to report any pregnancy to the research staff immediately * Willing and able to comply with study requirements and follow up instructions * Patient with known history of endometriosis or polycystic ovarian syndrome * If subject is planning to pursue pregnancy: presence of at least unilateral tubal patency (with any clinically acceptable methods) Exclusion Criteria: * Currently pregnant or breast-feeding * Has a history of, or evidence of current gynecologic malignancy, breast cancer or other estrogen responsive cancer or any other malignancy within the past five years * Subjects with FMR1 premutation (fragile X syndrome), a BMP15 mutation or family history of a first degree relative with POI * Presence of adnexal masses indicating the need for further evaluation * Major mental health disorder that precludes participation in the study * Active substance abuse or dependence * Current or recent (within the past 2 weeks) use of the following medications: Oral or systemic corticosteroids, Hormones (estrogen, progestin, oral contraceptives), Danazol, anticoagulants, herbal or botanical supplements with possible hormonal effects. Washout will be allowed (2 weeks from screening) * Subjects under hormonal treatments including hormone replacement therapy (HRT) for osteoporosis, cardiovascular disease, or recalcitrant vasomotor symptomatology within 3 months from screening * Subjects with a history of breast cancer or other estrogen responsive cancer within 5 years from screening * Subjects with existing malignant neoplasm, under active management for malignant neoplasm or under active surveillance for malignant neoplasm within 5 years from screening * Subjects with history of thromboembolic events such as pulmonary embolism, stroke, or ischemic heart disease * Subjects with uncontrolled hypertension, kidney disease, liver disease, or polycystic ovary syndrome (PCOS) as defined below: * Uncontrolled hypertension: Systolic BP ≥ 140 and/or Diastolic BP ≥90 in patients taking anti-hypertensive treatment * Kidney Disease: an estimated glomerular filtration rate (eGFR) \< 60 ml/min/1.73 m\^2 (Incase the result is above/below acceptable range, one repeat test is acceptable) * Liver Disease: Serum aminotransferase (ALT or AST) levels \> 2x ULN * PCOS criteria: Oligo-anovulation (Irregular periods), antral follicle count (AFC) \>12 measuring 2-9mm, hyperandrogenism (elevated testosterone and DHEA levels), clinical hirsutism * Subjects with untreated endocrinopathies including Cushing's disease, thyroid disease, congenital adrenal hyperplasia and hyperprolactinemia * Subjects with intra-uterine devices (IUDs) * Subjects who are allergic to low-molecular-weight heparin sodium or human albumin * Medical conditions that are contraindicated in pregnancy * Type I or Type II diabetes mellitus, or if receiving antidiabetic medications within 3 months from screening * Known anemia (Hemoglobin \< 11 g/dL) * History of deep venous thrombosis, and/or pulmonary embolus * History of cerebrovascular disease * History of contrast media allergy * Known heart disease (New York Heart Association Class II or higher) * Known Liver disease (defined as Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) \>2 times normal, or total bilirubin \>2.5mg/dL) * Known Renal disease (defined as Blood urea nitrogen (BUN) \>30 mg/dL or serum creatinine \> 1.6 mg/dL)

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'This is a dose escalation study. The study participants are organized in groups of 3 where each participant will receive one study treatment.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 9, 'type': 'ESTIMATED'}}

2024-01-03