An interventional study of Papilozumib vaginal gel and Papilozumib oral supplement in Human Papillomavirus Infection and Human Papillomavirus Infections, sponsored by Hifas da Terra S.L.. Not yet recruiting at 6 sites in Spain. Open to female participants aged 30 Years to 50 Years. Per ClinicalTrials.gov, last updated 2026-10-05.
Sponsored by Hifas da Terra S.L. · Not applicable, Interventional, and Treatment
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 HPV 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.
576 studies on the registry are indexed under Papillomavirus Infections; 132 are open to participants now.
This study's planned enrollment of 81 is below the median of 235 across 402 interventional studies indexed under Papillomavirus Infections.
Browse Papillomavirus Infections studies →Hifas da Terra S.L. is the lead sponsor of 5 studies on the registry; 1 is open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants receive Papilozumib® vaginal gel for 6 months. During the first 3 months, one single-dose vaginal applicator is administered daily for 21 days followed by 7 days without treatment. During the following 3 months, one applicator is administered on alternate days, excluding menstrual periods
Device: Papilozumib vaginal gel
Participants receive Papilozumib® vaginal gel for 6 months using the same regimen as the vaginal-gel-only arm. Participants also receive oral Papilozumib® for 6 months, administered as two capsules while fasting and one capsule before dinner each day, separated from meals.
Device: Papilozumib vaginal gel · Dietary Supplement: Papilozumib oral supplement
Participants receive usual clinical practice without Papilozumib® vaginal gel or oral Papilozumib® supplementation. Participants undergo the study assessments and follow-up procedures specified in the protocol.
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.
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.
Exocervical mucosal restoration score at Day 30
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.
Time frame: Day 30 after treatment initiation
Participants with concordant cytology and colposcopy at Day 30
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.
Time frame: Day 30 after treatment initiation
Exocervical mucosal restoration score at follow-up visits
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.
Time frame: Day 30 for Arms B and C; Month 3 and Month 6 for all arms
Percentage of participants with concordant cytology and colposcopy findings
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.
Time frame: Day 30 for Arms B and C; Month 3 and Month 6 for all arms
Percentage of participants with normalization of abnormal cervical cytology
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.
Time frame: Day 30, Month 3, and Month 6
Percentage of participants with complete Human Papillomavirus Virus clearance
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.
Time frame: Month 6
Percentage of participants with partial Human Papillomavirus Virus clearance
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.
Time frame: Month 6
Change from baseline in Vaginal Health Index score
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.
Time frame: Baseline, Day 30, Month 3, and Month 6
Participant-reported treatment satisfaction score
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.
Time frame: Day 30, Month 3, and Month 6
Percentage of participants by vaginal gel adherence category
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.
Time frame: Day 30, Month 3, and Month 6
Percentage of participants by oral supplement adherence category
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.
Time frame: Day 30, Month 3, and Month 6
Number of participants with at least one adverse event
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.
Time frame: From randomization through Month 6
Participant-reported treatment tolerability score
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.
Time frame: Day 30, Month 3, and Month 6
Vaginal microbiota community state type
Vaginal microbiota will be assessed by shotgun metagenomic sequencing and classified according to Community State Type (CST). Categories are: CST I, dominated by Lactobacillus crispatus; CST II, dominated by Lactobacillus gasseri; CST III, dominated by Lactobacillus iners; CST IV, characterized by low Lactobacillus abundance and the presence of anaerobic and facultative anaerobic microorganisms; and CST V, dominated by Lactobacillus jensenii. The distribution of participants across CST categories will be reported at each assessment.
Time frame: Baseline and Month 6
Intestinal microbiota Shannon diversity index
Intestinal microbiota will be assessed in stool samples using shotgun metagenomic sequencing. Microbial diversity will be summarized using the Shannon diversity index. The Shannon diversity index will be reported at each assessment, with higher values indicating greater microbial diversity.
Time frame: Baseline, Month 3, and Month 6
Plan to share: No — No individual participant data will be made available. The study protocol did not establish a prospective plan, repository, data dictionary, access criteria, or governance process for sharing participant-level data with external researchers. Study data will be maintained confidentially and handled in accordance with applicable data-protection requirements. Only aggregate, non-identifiable study results may be reported.
No publications or documents are linked to this record.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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