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

Primary Purpose

Premature Ovarian Insufficiency, Diminished Ovarian Reserve

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
EV-Pure™
Sponsored by
Vitti Labs, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Premature Ovarian Insufficiency

Eligibility Criteria

18 Years - 43 Years (Adult)FemaleDoes not accept 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)

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Treatment Arm

    Arm Description

    Outcomes

    Primary Outcome Measures

    Evaluate the safety of EV-Pure™ treatment on ovarian function recovery in patients with idiopathic and other types of premature ovarian insufficiency and low ovarian reserve.
    The primary endpoint is the incidence of any treatment-emergent adverse events.

    Secondary Outcome Measures

    Determine the efficacy of EV-Pure™ treatment in patients with POI and low ovarian reserve
    The secondary endpoint is 50% reduction in follicle stimulating hormone (FSH) values, 30% increase in anti-Müllerian hormone (AMH) and estradiol levels, and increased antral follicle count (AFC).

    Full Information

    First Posted
    September 20, 2023
    Last Updated
    October 2, 2023
    Sponsor
    Vitti Labs, LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06072794
    Brief Title
    A Proof of Concept Study to Evaluate Exosomes From Human Mesenchymal Stem Cells in Women With Premature Ovarian Insufficiency (POI)
    Acronym
    VL-POI-01
    Official Title
    A Proof of Concept Study to Evaluate Exosomes From Human Mesenchymal Stem Cells in Women With Premature Ovarian Insufficiency (POI)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 2023 (Anticipated)
    Primary Completion Date
    October 2025 (Anticipated)
    Study Completion Date
    December 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Vitti Labs, LLC

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The ROSE-2 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.
    Detailed 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. EV-Pure™ 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 EV-Pure™ 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 EV-Pure™. Participant duration will be approximately 12 months.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Premature Ovarian Insufficiency, Diminished Ovarian Reserve

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Single Group Assignment
    Model Description
    This is a dose escalation study. The study participants are organized in groups of 3 where each participant will receive one study treatment.
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    9 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Treatment Arm
    Arm Type
    Experimental
    Intervention Type
    Drug
    Intervention Name(s)
    EV-Pure™
    Intervention Description
    EV-Pure™ is a decellularized product consisting of proteins, lipids, and nucleic acids derived from human placenta mesenchymal stem cells.
    Primary Outcome Measure Information:
    Title
    Evaluate the safety of EV-Pure™ treatment on ovarian function recovery in patients with idiopathic and other types of premature ovarian insufficiency and low ovarian reserve.
    Description
    The primary endpoint is the incidence of any treatment-emergent adverse events.
    Time Frame
    2 years
    Secondary Outcome Measure Information:
    Title
    Determine the efficacy of EV-Pure™ treatment in patients with POI and low ovarian reserve
    Description
    The secondary endpoint is 50% reduction in follicle stimulating hormone (FSH) values, 30% increase in anti-Müllerian hormone (AMH) and estradiol levels, and increased antral follicle count (AFC).
    Time Frame
    2 years

    10. Eligibility

    Sex
    Female
    Gender Based
    Yes
    Gender Eligibility Description
    Females with premature ovarian insufficiency
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    43 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    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)
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Mukesh Kumar, PhD
    Phone
    2407504893
    Email
    mkumar@fdamap.com

    12. IPD Sharing Statement

    Learn more about this trial

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

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