Live Double Combined Lactobacillus Capsule for Vaginal Use（IIa）

A Multicenter, Randomized, Double-Blind, Metronidazole-Controlled Phase IIa Clinical Study on the Safety and Tolerability of Dual Live Lactobacilli-containing Vaginal Capsules in the Treatment of Bacterial Vaginosis

This is a mutilcenter, randomized, double-blind, Metronidazole controlled phase lIa clinical study to evaluate the safety and tolerability of dual - live lactobacilli-containing vaginal capsules for the treatment of Bacterial Vaginosis.

This phase of research adopts a mutilcenter, randomized, double-blind, Metronidazole controlled, dose-escalation, and multiple administration design. From May 2021 to July 2022, 60 subjects with BV were planned to be enrolled in multiple hospitals across the country. The test drug, a dual live bacteria formulation, was set up in three dose groups (1×10⁷ CFU/capsule, 1×10⁸ CFU/capsule, and 1×10⁹ CFU/capsule), with metronidazole tablets as the positive control in each group. Each group was planned to include 20 subjects, who were randomly assigned to the test group or the control group in a 3:1 ratio. A randomization table was generated using SAS 9.4, with each group randomized independently and enrolled in ascending order of dose according to the principle of dose escalation. Only after the current dose group completed the safety observation on Day 9 and confirmed to be safe and tolerable, could enrollment in the higher dose group be initiated.

Inclusion Criteria:

1. Female, aged 18-50 years (inclusive), with prior sexual experience, willing to undergo vaginal drug administration, and agreeing to refrain from using intravaginal products (such as contraceptive creams, gels, foams, sponges, lubricants, douches, tampons, etc.) not specified in the study throughout the entire trial period.
2. Having a regular menstrual cycle (21-35 days).
3. Clinical diagnosis of bacterial vaginosis (BV), defined as meeting at least three of the Amsel criteria, with clue cells exceeding 20% of the total vaginal epithelial cells, and a Nugent score ≥ 7.
4. Able to understand and voluntarily sign the informed consent form.

Exclusion Criteria:

1. Individuals with a history of allergies or known hypersensitivity to any known component of the investigational product.

2. Known current diagnosis of pelvic inflammatory disease, cervicitis, or acute urogenital infection.

3. Diagnosis of vulvovaginal candidiasis (VVC), trichomonal vaginitis (TV), or aerobic vaginitis (AV, with a score ≥5).

4. Use of vaginal douching or other intravaginal treatments within 14 days prior to screening, or anticipated use during the trial period.

5. Known diagnosis of uterine fibroids, endometrial hyperplasia, or adenomyosis requiring intervention, as assessed by the investigator.

6. Patients who have used topical or systemic antimicrobial or antimycotic agents within 14 days prior to screening, or are anticipated to require such treatment during the trial period.

7. History of gynecological surgery within 2 months prior to screening.

8. Vaginal speculum examination at screening reveals significant vaginal mucosal damage (e.g., mucosal edema, congestion, ulceration, erosion).

9. History of major diseases affecting the cardiovascular, hepatic, renal, pulmonary, gastrointestinal, neurological, metabolic, urogenital, endocrine, or psychiatric systems, which in the investigator's judgment may compromise the subject's safety.

10. Any of the following laboratory findings at screening:

    Hemoglobin (HGB) < 100 g/L; White blood cell (WBC) count < 3.5 × 10⁹/L, or neutrophil count (NEUT) < 1.5 × 10⁹/L; Platelet (PLT) count < 80 × 10⁹/L; Serum creatinine (Cr) > 1.5 × upper limit of normal (ULN); Blood urea nitrogen (BUN) > 1.5 × ULN; Alanine aminotransferase (ALT) > 1.5 × ULN; Aspartate aminotransferase (AST) > 1.5 × ULN; Alkaline phosphatase (ALP) > 1.5 × ULN; Total bilirubin (TBIL) > 1.5 × ULN.

11. Participation in a clinical study within 3 months prior to screening.

12. Planning pregnancy within 2 months before screening to 6 months after the trial, or positive pregnancy test at screening.

13. Termination of pregnancy within 60 days prior to screening.

14. Lactating or postmenopausal women.

15. Physical conditions, concurrent surgeries, medications, or clinically significant abnormal laboratory findings that may affect the evaluation of the investigational product, as determined by the investigator.

16. Any other circumstances deemed unsuitable for participation in this study by the investigator.