Human Papillomavirus Infection, Human Papillomavirus Infections
Conditions
Keywords
Human Papillomavirus, HPV, Exocervical Mucosal Restoration, Cervical Cytology, ASC-US, Low-Grade Squamous Intraepithelial Lesion, LSIL, Atypical Glandular Cells, AGC, HPV Clearance, Vaginal Health, Vaginal Microbiota, Gut Microbiota, Papilozumib, Vaginal Gel
Brief summary
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.
Detailed description
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.
Interventions
DEVICEPapilozumib vaginal gel
Papilozumib® is a single-dose vaginal gel administered for 6 months. During the first 3 months, participants apply one vaginal applicator daily for 21 days followed by 7 days without treatment. During the following 3 months, participants apply one applicator on alternate days, excluding menstrual periods.
DIETARY_SUPPLEMENTPapilozumib oral supplement
Papilozumib® oral supplement is provided as capsules containing mushroom extracts, vitamins, minerals, and probiotics. Participants take three capsules daily for 6 months: two capsules while fasting and one capsule before dinner, separated from meals.
Sponsors
Hifas da Terra S.L.
Adknoma Health Research
Eurofins
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are randomized in a 1:1:1 ratio to one of three parallel groups: Papilozumib® vaginal gel, Papilozumib® vaginal gel plus oral Papilozumib® supplement, or usual clinical practice without study treatment. Randomization is stratified by study center using permuted blocks of three.
Eligibility
Sex/Gender
FEMALE
Age
30 Years to 50 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Exocervical mucosal restoration score at Day 30 | Day 30 after treatment initiation | Exocervical mucosal restoration will be assessed by colposcopy in participants assigned to Papilozumib® vaginal gel alone. The investigator will score the exocervical mucosa using a 5-point scale: 1, severe ectopia with bleeding; 2, severe or extensive ectopia involving more than 50% from the external cervical opening; 3, moderate ectopia involving 25% to 50%; 4, mild ectopia involving less than 25%; and 5, no ectopia. Higher scores indicate greater exocervical mucosal restoration. |
| Participants with concordant cytology and colposcopy at Day 30 | Day 30 after treatment initiation | In participants assigned to Papilozumib® vaginal gel alone, the investigator will record whether the cervical cytology result is concordant with the colposcopic finding using a "Yes" or "No" response. The outcome will be reported as the percentage of participants with concordant findings. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exocervical mucosal restoration score at follow-up visits | Day 30 for Arms B and C; Month 3 and Month 6 for all arms | Exocervical mucosal restoration will be assessed by colposcopy using the 5-point scale: 1, severe ectopia with bleeding; 2, severe or extensive ectopia involving more than 50%; 3, moderate ectopia involving 25% to 50%; 4, mild ectopia involving less than 25%; and 5, no ectopia. Higher scores indicate greater mucosal restoration. The Day 30 assessment applies to the vaginal gel plus oral supplement arm and the usual clinical practice arm. Month 3 and Month 6 assessments apply to all study arms. |
| Percentage of participants with concordant cytology and colposcopy findings | Day 30 for Arms B and C; Month 3 and Month 6 for all arms | The investigator will record whether the cervical cytology result is concordant with the colposcopic finding using a Yes or No response. The outcome will be reported as the percentage of participants with concordant findings. The Day 30 assessment applies to Arms B and C, and the Month 3 and Month 6 assessments apply to all arms. |
| Percentage of participants with normalization of abnormal cervical cytology | Day 30, Month 3, and Month 6 | Among participants with abnormal cervical cytology at baseline, normalization is defined as a change from atypical squamous cells of undetermined significance (ASC-US), low-grade squamous intraepithelial lesion (LSIL), or atypical glandular cells (AGC) to normal cervical cytology, with a concordant colposcopic finding. The reported outcome will be the percentage of participants meeting this combined definition of cytological normalization; colposcopic concordance will not be reported as a separate measurement within this outcome. |
| Percentage of participants with complete Human Papillomavirus Virus clearance | Month 6 | Complete human papillomavirus clearance will be assessed using genotyped polymerase chain reaction (PCR) testing. Complete clearance is defined as a negative HPV test or disappearance of all HPV genotypes detected at baseline. The reported value will be the percentage of participants meeting the definition of complete HPV clearance. |
| Percentage of participants with partial Human Papillomavirus Virus clearance | Month 6 | Partial human papillomavirus clearance will be assessed using genotyped polymerase chain reaction (PCR) testing. Partial clearance is defined as disappearance of at least one HPV genotype detected at baseline. The reported value will be the percentage of participants meeting the definition of partial HPV clearance. |
| Change from baseline in Vaginal Health Index score | Baseline, Day 30, Month 3, and Month 6 | Vaginal health will be assessed using the Bachmann Vaginal Health Index. The change from the baseline score will be calculated at each follow-up assessment. |
| Participant-reported treatment satisfaction score | Day 30, Month 3, and Month 6 | Participants in the two treatment arms will rate their satisfaction with the assigned treatment using a 7-point response scale ranging from 1, satisfied, to 7, not at all satisfied. Lower scores indicate greater satisfaction. |
| Percentage of participants by vaginal gel adherence category | Day 30, Month 3, and Month 6 | Adherence to Papilozumib vaginal gel will be assessed in participants assigned to Arms A and B using treatment dispensing and return records and the participant treatment calendar. Vaginal gel adherence will be categorized as poor, less than 50%; moderate, 50% to less than 75%; good, 75% to less than 90%; or very good, 90% or greater. |
| Percentage of participants by oral supplement adherence category | Day 30, Month 3, and Month 6 | Adherence to the Papilozumib oral supplement will be assessed in participants assigned to Arm B using treatment dispensing and return records and the participant treatment calendar. Oral supplement adherence will be categorized as poor, less than 50%; moderate, 50% to less than 75%; good, 75% to less than 90%; or very good, 90% or greater. |
| Number of participants with at least one adverse event | From randomization through Month 6 | Safety will be assessed as the number of participants who experience at least one adverse event after randomization. A participant will be counted once in this outcome regardless of the number of adverse events experienced. Characteristics of individual adverse events, including their nature and severity, will be evaluated descriptively and are not separate measurements within this Outcome Measure. |
| Participant-reported treatment tolerability score | Day 30, Month 3, and Month 6 | Participants in the two treatment arms will rate tolerability using a 5-point scale: 1, very good; 2, good; 3, neutral; 4, poor; and 5, very poor. Arm A participants will rate the vaginal gel, and Arm B participants will rate the vaginal gel plus oral supplement combination. Lower scores indicate better tolerability. |
Countries
Spain
Contacts
CONTACTMayte Monreal Núñez
Outcome results
None listed