Evaluation of BGY-1601-VT Vaginal Tablet in Treating Acute Vaginal Infections in Women: A Randomized, Double-Blind, Placebo-Controlled Study

The primary objective of this study is to evaluate the **efficacy** of BGY-1601-VT, a live biotherapeutic product, in treating acute vaginal infection. This will be assessed by comparing two dosing regimens of BGY-1601-VT against a placebo in women diagnosed with Bacterial Vaginosis (BV), Vulvovaginal Candidiasis (VVC), or a mixed infection (BV+VVC). The clinical relevance of this objective lies in determining the potential of BGY-1601-VT as a first-line monotherapy for these common gynecological infections, which can significantly impact women's health and quality of life.

Secondary objectives include: - Comparing the efficacy of BGY-1601-VT dosing regimen #1 versus placebo, dosing regimen #2 versus placebo, and dosing regimen #1 versus dosing regimen #2 in treating acute vaginal infection. - Assessing the safety of BGY-1601-VT in both dosing regimens and the safety of the placebo. - Comparing the evolution of **Lacticaseibacillus rhamnosus** Lcr35 within the vaginal microbiome between the two dosing regimens.

The clinical trial focuses on evaluating the efficacy of BGY-1601-VT in treating **acute vaginal infections** such as Bacterial Vaginosis (BV) and Vulvovaginal Candidiasis (VVC) in women. The study population comprises post-menarche and premenopausal women aged 18 to 50 years, all of whom are in good general and mental health as assessed by the investigator. Participants are exclusively female, with no male subjects involved, and the trial does not include any vulnerable populations. The selection criteria ensure that participants have a confirmed diagnosis of BV, VVC, or a mixed infection, and are not at risk of pregnancy, as confirmed by a negative pregnancy test. The sponsor has not provided information regarding the total number of participants. Participants are expected to comply with the trial protocol and are required to have health insurance coverage. Lifestyle factors such as diet and physical activity are not specified as part of the trial's considerations.

The clinical trial is designed to evaluate the **efficacy** and safety of a live biotherapeutic product, BGY-1601-VT, in women with acute vaginal infection. This study is a **randomized, double-blind, placebo-controlled** trial, which aims to compare the effects of BGY-1601-VT against a placebo. The trial will involve post-menarche and premenopausal women aged 18 to 50 years who have been diagnosed with bacterial vaginosis, vulvovaginal candidiasis, or a mixed infection. The trial is expected to commence recruitment on June 14, 2024, and conclude by June 30, 2026.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, such as a negative pregnancy test and good general health. Following the screening, participants will be randomized to receive either the investigational product or placebo. The primary endpoint is the percentage of responders with clinical cure at the second visit (V2), which occurs 7 days after treatment initiation. Secondary endpoints include symptom improvement and the time to resolution of symptoms.

Throughout the trial, participants will attend follow-up visits to monitor their response to treatment and any adverse events. The end-of-study visit will assess the overall outcomes and gather final data. The expected duration of participant involvement is approximately 7 days, with additional time for follow-up assessments. Participants may be withdrawn from the study if they require rescue therapy before V2 or if they experience significant adverse events. The trial will ensure adherence to protocol procedures and ethical standards, with informed consent obtained from all participants.

The clinical trial involves the evaluation of **BGY-1601-VT**, a live biotherapeutic product formulated as a vaginal tablet. The active substance in BGY-1601-VT is **Lactobacillus rhamnosus**, strain LCR35, live. This product is administered via vaginal use. The dosing regimen includes two different schedules, which are compared against a placebo to assess efficacy in treating acute vaginal infections, specifically **Bacterial Vaginosis (BV)**, **Vulvovaginal Candidiasis (VVC)**, or mixed infections (BV+VVC). The administration frequency and specific dosing schedules are determined as per the trial protocol, ensuring participant compliance is monitored throughout the study.

The placebo used in this study is a tablet designed for vaginal administration, composed of excipients without any active ingredient. The excipients include microcrystalline cellulose (658.14 mg), hypromellose (25.86 mg), calcium hydrogen phosphate dihydrate (172.4 mg), magnesium stearate (4.31 mg), and yellow iron oxide (1.29 mg). The placebo is administered in a manner identical to the experimental treatment to maintain the double-blind nature of the study. Compliance with the placebo administration is monitored to ensure the integrity of the trial results.

The efficacy of the investigational product BGY-1601-VT, a **Live Biotherapeutic Product**, will be assessed in a randomized, double-blind, placebo-controlled clinical trial involving women with acute vaginal infections, specifically Bacterial Vaginosis (BV), Vulvovaginal Candidiasis (VVC), or mixed infections (BV+VVC). The primary endpoint for evaluating efficacy is the percentage of responders, defined as participants achieving clinical cure at the second visit (V2) without the initiation of rescue therapy before this time point. Secondary endpoints include the percentage of participants with clinical cure and improved symptoms at various time points, as assessed by both self-assessment using the PGI-C scale and investigator assessment using the CGI-C scale, with scores of ≤ 2 indicating improvement. Additional secondary endpoints involve the evolution of symptoms such as itching, burning, pain, and vaginal discharge, as well as the time to resolution and recurrence of symptoms, and the time to initiation of rescue therapy.

Quantitative assessments will include the quantification of Lcr35 in the vaginal microbiota using quantitative polymerase chain reaction (qPCR) on vaginal secretions at specified time points. The trial will also monitor the number of adverse events, categorized by their nature (systemic or local), severity, and whether they are treatment-emergent. Efficacy assessments will be conducted at multiple time points, including 7 days (-1/+3) after treatment initiation, to ensure comprehensive evaluation of the treatment's impact on the acute vaginal infection symptoms and overall clinical outcomes.