Efficacy and Safety of Vaginal Lactobacillus Dual Probiotic Capsules in Bacterial Vaginosis

Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Study on the Efficacy and Safety of Vaginal Lactobacillus Dual Probiotic Capsules for the Treatment of Bacterial Vaginosis

Primary Objective: To confirm that the clinical cure rate of Vaginal Lactobacillus Dual Probiotic Capsules for bacterial vaginosis (BV) is superior to placebo at the 21-30 day post-treatment visit (Day 21 to Day 30).

Key Secondary Objective: To compare the clinical cure rate of Vaginal Lactobacillus Dual Probiotic Capsules versus placebo for BV at the 15-18 day post-treatment visit (Day 15 to Day 18).

Other Secondary Objectives: 1) To comprehensively assess the therapeutic efficacy of the study drug versus placebo for BV at Day 15 to 18 and Day 21 to 30; 2) To evaluate the safety profile of the study drug for BV treatment compared with placebo, including adverse events and clinical laboratory findings.

Study Design & Randomization: This is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical trial. An independent biostatistician generated the subject and drug randomization lists via SAS software, which were imported into an Interactive Web Response System (IWRS). Investigators at each site obtain randomization and drug numbers through the IWRS for subject allocation.

Blinding & Allocation Concealment: Double-blinding is implemented for both investigators and subjects. The study drug and placebo are identical in appearance, shape, specification, and dosage form. Blinding procedures are performed by personnel unrelated to the trial, with a complete and detailed record of the entire blinding process maintained throughout the study.

This Phase III clinical trial is designed to evaluate the superior efficacy and safety of Vaginal Lactobacillus Dual Probiotic Capsules for the treatment of bacterial vaginosis (BV) in adult women, with a placebo control and double-blind design to minimize bias in efficacy and safety assessment. BV is a common vaginal dysbiosis caused by the imbalance of vaginal microflora, characterized by the reduction of dominant Lactobacillus and overgrowth of anaerobic bacteria, and clinical treatment options with sustained efficacy and good safety are still in demand.

The study adopts a randomization mode based on an Interactive Web Response System (IWRS), which ensures the randomness and concealment of subject allocation. The randomization list is generated by an independent biostatistician using SAS statistical software, with no access to the list for on-site investigators to avoid selection bias. Strict double-blinding is maintained for the entire study period: the study drug and matching placebo are manufactured to be consistent in all physical characteristics, and the drug packaging and labeling are completed by professional personnel not involved in clinical trial implementation, follow-up, or assessment. The blinding code will be kept confidential and only unblinded in the event of a serious adverse event requiring urgent medical judgment, or after the completion of the entire study and database locking for statistical analysis.

Study interventions are administered intravaginally as per the trial protocol, with clinical efficacy assessed at two key time points: the early post-treatment visit (Day 15-18) to evaluate the short-term therapeutic effect, and the primary efficacy visit (Day 21-30) to confirm the sustained clinical cure effect-both core time points are set based on the natural course of BV and the metabolic characteristics of vaginal probiotics, to fully reflect the drug's regulatory effect on vaginal microflora. Efficacy assessment is based on the Amsel criteria (the gold standard for clinical diagnosis of BV) and Nugent score (quantitative microflora assessment), with consistent and standardized assessment criteria and operating procedures across all participating centers to ensure the comparability and reliability of efficacy data.

Safety assessment is conducted throughout the entire study period, including screening, treatment, and follow-up visits, with comprehensive collection of adverse events (AEs), serious adverse events (SAEs), physical examinations, gynecological specific examinations, and clinical laboratory tests (blood routine, urine routine, liver and kidney function, etc.). All safety data are recorded in the case report form (CRF) in a timely and accurate manner, and assessed for causality, severity, and relationship with the study drug by the investigator and clinical trial supervisor.

The multicenter design of the study ensures the representativeness of the study population, with participating centers selected for their rich clinical experience in the diagnosis and treatment of gynecological infectious diseases, and all investigators and research staff receive unified training and qualification confirmation before the trial initiation to ensure the standardization and consistency of trial implementation in accordance with the study protocol, Good Clinical Practice (GCP), and relevant regulatory requirements.

Inclusion Criteria:

1. The subjects fully understand the purpose, nature, methods, and potential adverse reactions of the trial, voluntarily participate in the study, and sign an informed consent form before the trial begins;

2. Females aged ≥18 years and ≤50 years, with normal and regular menstrual cycles;

3. Have a history of sexual activity, are willing to undergo vaginal medication, and agree to avoid using other intravaginal products (such as contraceptive creams, gels, foams, sponges, lubricants, douches, tampons, etc.) and sexual activity throughout the entire trial period;

4. Clinically diagnosed with Bacterial Vaginosis (BV), requiring the simultaneous satisfaction of all four Amsel criteria:

   • Positive clue cells;
   • Positive amine (whiff) test;
   • Vaginal discharge pH > 4.5;
   • Vaginal discharge is homogeneous, thin, and grayish-white in appearance.

5. Nugent score ≥ 7 points.

Exclusion Criteria:

1. Known allergy to any component of the investigational drug;
2. Known current diagnosis of pelvic inflammatory disease, cervicitis, or acute urogenital tract infections;
3. Presence of vulvovaginitis caused by other infectious etiologies, such as vulvovaginal candidiasis (VVC), trichomonal vaginitis (TV), aerobic vaginitis (AV score ≥3), gonorrhea, Chlamydia trachomatisinfection, etc.;
4. Pelvic examination at screening reveals the presence of condyloma acuminata;
5. History of complicated or recurrent VVC within 1 year prior to screening;
6. Known diagnosis of uterine myoma or adenomyosis requiring interventional treatment, as judged by the investigator;
7. Vaginal speculum examination at screening shows significant vaginal mucosal injury (e.g., mucosal edema, ulceration, erosion);
8. History of significant diseases involving the cardiovascular, hepatic, renal, pulmonary, gastrointestinal, neurological, metabolic, urogenital, endocrine, or psychiatric systems, which in the investigator's judgment may affect participant safety;
9. Use of vaginal douching or other intravaginal treatments (e.g., products like Jie Er Yin, Jie Yin Kang) within 72 hours prior to dosing or anticipated use during the trial period;
10. Received antibiotic or antifungal treatment (systemic and/or intravaginal) within 2 weeks prior to dosing;
11. Current use of long-acting injectable contraceptives or long-acting oral contraceptives at screening;
12. History of gynecological surgery or common procedures that may affect the vaginal microenvironment within 2 months prior to screening (including but not limited to Bartholin's cyst/abscess incision, intrauterine device removal/insertion, cervical or vaginal wall biopsy, cervical conization or loop electrosurgical excision procedure [LEEP]);
13. Virological testing at screening is positive for syphilis or HIV;
14. Positive pregnancy test at screening; or history of pregnancy termination within 2 months prior to screening; or women of childbearing potential who, in the investigator's judgment, cannot use a medically approved, reliable method of contraception from the time of signing the informed consent form until 3 months after the last dose of the study drug;
15. Women who are pregnant or breastfeeding;
16. Participation in other drug or device clinical trials within 3 months prior to dosing, involving the use of investigational drugs or devices;
17. Any other medical condition that, in the investigator's judgment, may interfere with the assessment of this study.