A Randomized, Double-blind, Three Arm, Multi-center Phase 2 Study to Investigate the Molecular Efficacy and Safety of FB301/Chlorhexidine Compared With FB301/Sham and Placebo/Sham in a Mock FET Cycle in Female Participants 18-40 Years of Age With Asymptomatic Vaginal Molecular Dysbiosis Planning to Undergo a Frozen Embryo Transfer (FET) Cycle
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 5
- 主要终点
- Proportion of participants with ≥90% combined relative abundance of Lactobacillus crispatus, L. jensenii, L. mulieris, L. gasseri, and L. paragasseri as measured by metagenomic sequencing.
研究概览
简要总结
The goal of this clinical trial is to evaluate FB301 during a mock frozen embryo transfer (FET) cycle in pre-menopausal women aged 18 to 40 years with a prior failed FET and a defined vaginal bacterial imbalance (dysbiosis).
The main question it aims to answer is:
• Does treatment with FB301 during a mock FET cycle change the proportion of participants who meet the predefined vaginal bacterial threshold compared with placebo?
Researchers will compare:
- FB301 given after an initial vaginal cleansing with chlorhexidine (an antiseptic solution),
- FB301 given after an initial vaginal cleansing with saline (saltwater), and
- A placebo capsule given after an initial vaginal cleansing with saline to determine whether these approaches affect vaginal bacterial composition and pregnancy outcomes.
Participants will take study treatment for 15 days during a "mock" FET cycle. In a mock cycle, participants receive the hormones needed to prepare the uterus for embryo transfer, but no embryo is transferred. After completing the mock cycle, participants will proceed with their planned frozen embryo transfer and will be followed during pregnancy until birth.
Participants will:
- Undergo a vaginal cleansing before receiving the first dose of FB301 or placebo
- Provide vaginal swab samples at up to 5 study visits
- Attend the study centre for up to 8 visits and participate in up to 4 follow-up phone calls
- Complete a mock FET cycle before proceeding with their planned frozen embryo transfer cycle
Participants who become pregnant will be followed until birth.
详细描述
Vaginal dysbiosis characterized by reduced relative abundance of Lactobacillus species has been associated with reproductive outcomes in women undergoing frozen embryo transfer (FET). This study evaluates the safety, tolerability, and molecular effects of FB301 in women undergoing FET who have no known underlying clinical gynecological conditions but are identified as having molecular dysbiosis by metagenomic sequencing of a vaginal swab collected at screening.
Participants will be randomized to one of three arms: (1) FB301 following a single initial vaginal cleansing with chlorhexidine (an antiseptic solution), (2) FB301 following a single sham cleansing with saline, or (3) placebo following sham cleansing. Cleansing occurs once prior to initiation of study treatment. Participants will then receive 15 days of study treatment during a mock frozen embryo transfer (FET) cycle in which participants receive hormonal preparation of the endometrium but no embryo is transferred. Following completion of the mock cycle, participants will proceed with their planned frozen embryo transfer during the subsequent menstrual cycle, in accordance with standard clinical practice. Participants who become pregnant will be followed until birth.
The primary objective is to evaluate whether treatment increases the proportion of participants achieving a predefined Lactobacillus-dominant vaginal bacterial profile following therapy. Secondary objectives include evaluation of biochemical pregnancy (confirmed by serum beta-hCG testing) and clinical pregnancy (confirmed by transvaginal ultrasound) following the subsequent planned FET cycle.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Able to understand the study and sign a consent form.
- •Is a woman aged 18 to 40 years.
- •Still has regular menstrual periods (pre-menopausal).
- •Has had at least one previous frozen embryo transfer (FET) that did not result in pregnancy within the past 3 years, and this was not due to either male infertility or blocked /damaged fallopian tubes.
- •Planning to have a frozen embryo transfer (FET) using one good-quality embryo (grade 3BB or higher) and are considered medically suitable to proceed.
- •Willing to have only one embryo transferred during the study cycle.
- •A vaginal swab taken at the first study visit shows a specific vaginal microbiome imbalance required for this study (vaginal molecular dysbiosis).
- •An ultrasound scan shows no problems with uterus or pelvis that would prevent pregnancy or greatly reduce the chance of pregnancy.
- •Recent fertility blood tests (within the last 6 months) show:
- •FSH less than 12 IU/L
- •AMH greater than 1 ng/mL
- •Body mass index (BMI) is between 18 and 38 kg/m².
- •From the first study treatment until the mock FET cycle, agrees to:
- •Avoid vaginal intercourse or use condoms (without spermicide or lubricant),
- •Avoid swimming or hot tubs,
- •Avoid using tampons, menstrual cups, sex toys, vaginal cleansers, lubricants, or other vaginal products unless approved by the study team.
- •Willing to answer questions about sexual and reproductive activity during the study.
- •Willing to provide vaginal swab samples at the clinic.
- •Willing to receive the first study treatment in the clinic and use the study treatment at home as instructed.
- •Screening blood tests are negative for hepatitis B, hepatitis C, HIV, and syphilis.
- •Willing to attend all study visits and follow-up assessments and provide information about pregnancy and newborn health outcomes.
排除标准
- •History of three or more failed frozen embryo transfers (FET) in the past 3 years.
- •Have a condition that weakens the immune system (such as uncontrolled diabetes, active cancer, or an organ transplant).
- •Currently taking medications that suppress the immune system (such as systemic steroids, biologics, chemotherapy, or transplant medications).
- •Is already pregnant before completing the mock FET cycle.
- •Test positive for a sexually transmitted infection (such as chlamydia, gonorrhea, Mycoplasma genitalium, or Trichomonas vaginalis).
- •Current vaginal yeast infection that requires treatment.
- •YCannot safely take the hormone medications required for a frozen embryo transfer (such as estradiol or progesterone).
- •Use of intravaginal progesterone gels or solutions.
- •Needs regular antibiotics or are likely to require antibiotics during the study.
- •Has taken oral, injectable, or vaginal antibiotics within 30 days before screening.
- •History of gynecological cancer or other significant gynecological condition that would make participation unsafe.
- •Has a medical condition that would make participation unsafe or difficult.
- •Has an unstable medical or psychiatric condition that could make it difficult to follow study requirements.
- •Has any other condition that could interfere with participation.
研究组 & 干预措施
FB301 / Chlorhexidine
干预措施: FB-301 (Drug)
FB301 / Chlorhexidine
干预措施: Chlorhexidine (0.5%) Vaginal Cleanse (Other)
FB301 / Sham
干预措施: FB-301 (Drug)
FB301 / Sham
干预措施: Sham vaginal cleanse (saline) (Other)
Placebo / Sham
干预措施: Sham vaginal cleanse (saline) (Other)
Placebo / Sham
干预措施: Placebo (Drug)
结局指标
主要结局
Proportion of participants with ≥90% combined relative abundance of Lactobacillus crispatus, L. jensenii, L. mulieris, L. gasseri, and L. paragasseri as measured by metagenomic sequencing.
时间窗: Baseline to Day 16 (Mock FET cycle)
Metagenomic sequencing is performed on cervical vaginal swab samples. Relative abundance is expressed as a percentage of bacterial sequencing reads that are assigned to a specific bacterial species.
次要结局
- Frequency and intensity of all treatment-emergent adverse events (TEAEs), adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest) AESI(Baseline to End of Study (up to neonatal follow-up assessment (Visit 11), approximately 10 months after FET))
- The incidence of early pregnancy loss, defined as a positive beta-hCG test (biochemical pregnancy) at 12-14 days after FET but no transvaginal ultrasound-confirmed fetal heartbeat at 5-6 weeks after FET (Visit 7)(5-6 weeks after FET)
- Clinical pregnancy rate following frozen embryo transfer (FET), defined as the presence of a fetal heartbeat confirmed by transvaginal ultrasound.(5-6 weeks after frozen embryo transfer (FET))
- Percentage change from baseline in relative abundance of Lactobacillus crispatus, L. jensenii, L. mulieris, L. gasseri, and L. paragasseri as measured by metagenomic sequencing.(Baseline to Day 16 (Mock FET cycle))
- Biochemical pregnancy rate following frozen embryo transfer (FET), defined as a positive serum beta-human chorionic gonadotropin (hCG) test.(12-14 days after frozen embryo transfer (FET))