Exploratory, Randomized, Multicenter, Open-Label, Controlled, Parallel-Group Clinical Study to Evaluate the Efficacy of Papilozumib® Vaginal Gel in the Restoration of the Exocervical Mucosa
This randomized, open-label, multicenter clinical study is designed to evaluate Papilozumib® vaginal gel in women aged 30 to 50 years who test positive for human papillomavirus (HPV) and present with either normal cervical cytology or cytological findings of atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), or atypical glandular cells (AGC), accompanied by corresponding colposcopic findings. Eighty-one participants will be randomly assigned in equal groups to receive either Papilozumib® vaginal gel, Papilozumib® vaginal gel plus an oral supplement, or standard clinical care without study treatment. All participants will be followed for six months. The primary objective is to assess exocervical mucosa restoration 30 days after treatment initiation using a 5-point colposcopic scale. Additional assessments include cervical cytology, HPV clearance, vaginal health, treatment adherence, satisfaction, tolerability, safety, and exploratory analyses of the vaginal and intestinal microbiota.
Persistent human papillomavirus infection may lead to cervical epithelial abnormalities. This exploratory study evaluates whether Papilozumib® vaginal gel helps restore the exocervical mucosa in HPV-positive women with normal, low-grade, or atypical cytological findings. Eligible participants will be randomly assigned in equal numbers to one of three groups: Papilozumib® vaginal gel, Papilozumib® vaginal gel plus an oral Papilozumib® supplement, or usual clinical practice without study treatment. The study is open-label, with randomization stratified by center. Participants in the vaginal gel groups will use one single-dose applicator daily for 21 days, followed by 7 days without treatment, during each of the first three months. For the next three months, the gel will be used on alternate days, except during menstrual periods. Those in the combined-treatment group will also take three oral capsules daily for six months. Assessments will occur at baseline, Day 30, Month 3, and Month 6. The primary outcome is the degree of exocervical mucosal restoration at Day 30, measured by colposcopy on a 5-point scale from severe ectopia and bleeding to no ectopia. Secondary outcomes include changes in colposcopic findings, normalization of cervical cytology, partial or complete HPV clearance by genotyped polymerase chain reaction, vaginal health, adherence, treatment satisfaction, tolerability, and adverse events. Exploratory assessments will analyze the vaginal microbiota at baseline and Month 6, and the intestinal microbiota at baseline, Month 3, and Month 6, using shotgun metagenomic sequencing.
Inclusion Criteria: * Female participant aged 30 to 50 years, inclusive. * Able to read and understand the participant information sheet and informed consent form. * Willing to participate and able to provide written informed consent. * Normal cervical cytology or cervical cytology showing atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), or atypical glandular cells (AGC), with corresponding colposcopic findings at baseline. * Cervical cytology obtained no more than 3 months before the baseline/randomization visit. * Positive test for human papillomavirus (HPV) by polymerase chain reaction (PCR) at baseline. * HPV PCR test obtained no more than 3 months before the baseline/randomization visit. * Exocervical mucosal restoration score of 3 or lower on the 5-point colposcopic scale at baseline. * Baseline colposcopy performed no more than 3 months before randomization; the score may be determined from previously recorded images when available in the medical record. * Considered by the investigator able to follow the study instructions, attend the required visits, and complete the study assessments.
Exclusion Criteria: * Clinically relevant immune-system disorder, autoimmune disease, or current treatment with immunosuppressive medication. * Systemic or local treatment with antibiotics, antifungal agents, or another treatment that may alter the microbiota within 4 weeks before baseline/randomization. * Undiagnosed abnormal genital bleeding during the 6 months before screening. * Symptomatic vulvovaginal infection. * Surgical cervical excision within the previous year, cervical conization within the previous 6 months, or previous total hysterectomy. * Previous gynecological cancer. * Current participation in another clinical study or participation in another clinical study within 4 weeks before screening. * Planned surgery that could prevent adherence to the study treatment schedule. * Use of vaginal contraceptives or other vaginal hormonal treatments. * Contraindication to the vaginal gel or known allergy to any of its components. * Pregnant, suspected to be pregnant, breastfeeding, or of childbearing potential and not using an effective contraceptive method.
[{"measure":"Exocervical mucosal restoration score at Day 30","timeFrame":"Day 30 after treatment initiation"},{"measure":"Participants with concordant cytology and colposcopy at Day 30","timeFrame":"Day 30 after treatment initiation"}]