A Proof of Concept Study to Evaluate Exosomes From Human Mesenchymal Stem Cells in Women With Premature Ovarian Insufficiency (POI) (VL-POI-01)

Vitti Labs

Status and phase

Suspended

Phase 1

Conditions

Diminished Ovarian Reserve

Premature Ovarian Insufficiency

Treatments

Drug: VL-PX10

Study type

Interventional

Funder types

Industry

Identifiers

NCT06072794

VL-POI-01

Details and patient eligibility

About

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.

Full description

Premature ovarian insufficiency (POI) is a devastating disease for young women who have not yet completed childbearing. The prevalence of this condition is on the rise due to the increasing number of cancer survivors and the delay in childbearing age. Current treatment options available are very limited. Stem cell therapy has been shown to be beneficial and effective in various disease processes and the safety has been assessed in multiple clinical trials. The regenerative potential of mesenchymal stem cells is increasingly attributed to the paracrine effects of exosomes. Exosomes consist of bioactive lipids, nucleic acids, and proteins which play a key role in intercellular communication. Exosome therapy is considered a safe and effective therapy since it offers a cell-free approach. VL-PX10 is a decellularized exosome product derived from human placental derived mesenchymal stem cells.

This interventional pilot study will investigate the ability of intravenous injection of VL-PX10 to restore steroidogenesis, folliculogenesis, and support quality of life improvement, resumption of menstruation, and reversal of infertility in patients with POI and diminished ovarian reserve.

This is an open label study. All patients entering this study will be treated with VL-PX10. Participant duration will be approximately 12 months.

Enrollment

9 estimated patients

Sex

Female

Ages

18 to 43 years old

Volunteers

No Healthy Volunteers

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)