Study of 2LPAPI® on the Clearance of Genital HR-HPV Infections. (PAPION)

August 25, 2026 updated by: Labo'Life

Randomized, Placebo-controlled, Double-blind Study to Evaluate 2LPAPI® Efficacy on the Clearance of Genital HR-HPV Infections.

Human papillomavirus (HPV) is a prevalent pathogen, the epidemiology of which has mostly been studied in the uterine cervix and the vagina.

In Belgium, since 2025, HPV testing has become the primary screening method for cervical cancer. For women between 30 and 64 years, a clinical guideline (March 2025) from Sciensano stated the following " The triage of HPV-positive women is based on HPV type and reflex cytology outcome as a threshold for colposcopy. In 30- to 64-year-olds, triage of HR-HPV non-16/18 positives consists of an initial reflex cytology, followed by another HPV test 12 months later if the first step demonstrated Negative for Intraepithelial Lesion or Malignancy (NILM). Women who test positive on the initial HR-HPV test for the most high-risk HPV types 16 or 18 are immediately referred for colposcopy. Besides colposcopy, a reflex cytology will be performed. ". Women from 25 to 29 years are recommended to undergo a cytology testing on cervical smear as primary screening method following Sciensano clinical guideline (March 2025) recommendations. If abnormalities are detected, a HPV testing is performed. For the two age groups, if low grade abnormalities are detected with a diagnosis of HR-HPV, a second triage is recommended at 12 months.

There is no treatment that is recommended during this lap time. The 2LPAPI® has been available for more than 20 years, and has received a marketing authorization in Belgium by the FAMHP. It is used as an immune regulator in the treatment of HR-HPV infections. Since 2LPAPI® has been made available, clinical observational data collected on treated patients have shown the beneficial effect on the clearance of HPV.

The purpose of this placebo-controlled trial is to evaluate the efficacy of 2LPAPI® on the clearance of genital HR-HPV infections.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study duration will be 72 months with 60 months of inclusion (that may be extended if the expected number of patients is not reached after 60 months) and 12 months of follow-up.

Patients aged between 25 and 45 years presenting a diagnosis of HR-HPV infection during the routine screening visit for cervical cancer prevention.

The total number of patients to include will be 284 with 142 patients per group.

Primary objective:

Comparison of the efficacy of 2LPAPI® versus placebo on the clearance of genital HR-HPV infections after 12 months of follow-up.

Secondary objectives:

Comparison of 2LPAPI® versus placebo on:

  • HR-HPV infection clearance rate at 6-month visits,
  • HR-HPV infection clearance rate by HPV type at 6-month and 12-month visits,
  • Evolution of cytology,
  • Normalization of cytology for the subpopulation of patients with a baseline non normal cytology,
  • Safety: adverse events (AEs) and serious adverse events (SAEs), considered as related or not to the study drug.

Treatment phase:

Group n°1 = 2LPAPI® (6 months of treatment) Group n°2 = Placebo (6 months of treatment) Post-treatment follow-up phase: 6 months. Treatment will be considered successful if the clearance of HR-HPV is done and the cytology is normal.

Study Type

Interventional

Enrollment (Estimated)

284

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Belgium
      • Brussels, Belgium, 1020
        • Recruiting
        • CHU Brugmann
        • Principal Investigator:
          • Catherine Van Pachterbeke, MD
        • Sub-Investigator:
          • Elie Finianos, MD
        • Contact:
          • Tatiana Besse-Hammer, MD
        • Sub-Investigator:
          • Tatiana Besse-Hammer, MD
      • Brussels, Belgium, 1000
        • Recruiting
        • CHU Saint-Pierre
        • Contact:
          • Yannick Manigart, Dr
        • Principal Investigator:
          • Yannick Manigart, Dr
        • Sub-Investigator:
          • Aurélie Joris, Dr
        • Sub-Investigator:
          • Christine Gilles, Dr
        • Sub-Investigator:
          • Charlotte Rousseau, Dr
      • Brussels, Belgium, 1000
        • Recruiting
        • Clinique St Jean
        • Contact:
          • Nathanaël DUBOIS
        • Sub-Investigator:
          • Jean-Paul VAN GOSSUM
        • Sub-Investigator:
          • Justine JEHOTTE
        • Sub-Investigator:
          • Andrea RADULESCU
        • Sub-Investigator:
          • Mathilde BARREIRA
        • Principal Investigator:
          • Nathanaël DUBOIS
      • Charleroi, Belgium, 6042
        • Active, not recruiting
        • Hôpital Civil Marie Curie ISPPC
      • Malmedy, Belgium, 4960
        • Active, not recruiting
        • Centre Hospital Reine Astrid Malmedy (CHRAM)
      • Namur, Belgium, 5000
        • Recruiting
        • Belgium
        • Contact:
          • Sarah MITRI
        • Principal Investigator:
          • Sarah MITRI
      • Namur, Belgium, 5000
        • Recruiting
        • Cabinet privé
        • Contact:
          • Benoit MOONS
        • Principal Investigator:
          • Benoit MOONS
      • Namur, Belgium
      • Ottignies, Belgium, 1340
        • Not yet recruiting
        • Clinique Saint-Pierre Ottignies (CSPO)
        • Contact:
          • Lucie Verreth, Dr
        • Principal Investigator:
          • Lucie Verreth, Dr
      • Tournai, Belgium, 7000
        • Recruiting
        • CHWAPI
        • Sub-Investigator:
          • Céline PETIT, MD
        • Sub-Investigator:
          • Sandra TASSART, MD
        • Principal Investigator:
          • Marc WAYEMBERGH, MD
        • Contact:
          • Marc WAYEMBERGH, MD
  • Romania
      • Bucharest, Romania, 022448
        • Not yet recruiting
        • Spitalul Nicolae Malaxa
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Women 25-45 years,
  • Women of childbearing age under effective contraception,
  • Patient with last cytology less than 3 years and normal or not more than LSIL or CIN I at the histology,
  • Patient with current cytology presenting normal, ASC-US, AGUS, LSIL, ASC-H, AGC or LSIL+ASC-H results or current diagnosis of CIN I at the histology,
  • Patient with HR-HPV diagnosis at the current cervical collection,
  • Patient reporting a current stable sexual relationship (steady sexual partner during study duration),
  • Patient having faculties to understand and respect the constraints of the study,
  • Signature of the Informed Consent Form.

Exclusion Criteria:

  • Pregnant or breastfeeding woman,
  • Patient presenting HSIL diagnosis at the cytology or CIN II or CIN III diagnosis at the histology,
  • Patient having received HPV vaccination in the last month,
  • Patient previously subject to total hysterectomy,
  • Patient under immunotherapy (including immunosuppressive treatment) or micro-immunotherapy received during last previous 6 months,
  • Patient with known lactose intolerance,
  • Patient who participated in a clinical study in the previous 3-months' period,
  • Patient who is not sufficiently motivated to engage in a follow-up period of 12 months, or likely to travel or to move before the end of the study,
  • Patient with severe immunodeficiency disease requiring long term treatment (*) or under chemotherapy or radiotherapy,
  • Patient under listed homeopathic or phytotherapy treatment (see protocol),
  • Patient using or addicted to recreational drugs.

(*) important renal or respiratory insufficiency, transplanted or grafted patients, HIV/AIDS, terminal cancer.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 2LPAPI® arm
The treatment schema consists in taking the content of one capsule a day, 15-30 minutes before breakfast, on an empty stomach, sequentially, according to capsules' numerical order: 1 through 10. When capsule number 10 is taken, capsule 1 of the next blister should be taken on the next day to continue the treatment. The duration of treatment will be 6 months of continuous intake of the content of 1 capsule/day.
Drug: 2LPAPI®
Treatment
Other Names:
  • 2LPAPI
Placebo Comparator: Placebo arm
The treatment schema consists in taking the content of one capsule a day, 15-30 minutes before breakfast, on an empty stomach, sequentially, according to capsules' numerical order: 1 through 10. When capsule number 10 is taken, capsule 1 of the next blister should be taken on the next day to continue the treatment. The duration of treatment will be 6 months of continuous intake of the content of 1 capsule/day.
Drug: Placebo
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Comparison of the efficacy of 2LPAPI® versus placebo on the clearance of genital HR-HPV infections after 12 months of follow-up.
Time Frame: 12 months
The primary objective of the study will be to compare the number of patients with positive HR-HPV infection status observed at 12 months and the number of patients with positive HR-HPV infection status observed at the inclusion.
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Occurrence of adverse events (AEs) and severe adverse events (SAEs), considered as related or not to the study drug
Time Frame: 6 months
6 months
Comparison of 2LPAPI® versus placebo on HR-HPV infection clearance rate at 6-month visits.
Time Frame: 6 months
The objective of this outcome will be to compare the number of patients with positive HR-HPV infection status observed at 6 months and the number of patients with positive HR-HPV infection status observed at the inclusion.
6 months
Comparison of 2LPAPI® versus placebo on HR-HPV infection clearance rate by HPV type at 6-month and 12-month visits.
Time Frame: 6 and 12 months
The objective of this outcome will be to compare the number of patients with specific type of HPV infection observed at 6 and 12 months and the number of patients with specific HPV infection status observed at the inclusion.
6 and 12 months
Evolution of cytology (normalization, stagnation or worsening) at 6-month and 12-month visits.
Time Frame: 6 and 12 months
The objective of this outcome will be to compare the evolution of the cytology at 6-month and 12-month visits.
6 and 12 months
Normalization of cytology at 6-month and 12-month visits for the subpopulation of patients with a baseline non-normal cytology.
Time Frame: 6 and 12 months
The objective of this outcome will be to compare the number of patients with a normal cytology at 6-month and 12-month visits in the subpopulation of patients with a baseline non-normal cytology.
6 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Labo'Life

Collaborators

CEBIS International

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 17, 2020

Primary Completion (Estimated)

October 30, 2027

Study Completion (Estimated)

March 30, 2028

Study Registration Dates

First Submitted

January 14, 2020

First Submitted That Met QC Criteria

January 16, 2020

First Posted (Actual)

January 18, 2020

Study Record Updates

Last Update Posted (Actual)

August 27, 2026

Last Update Submitted That Met QC Criteria

August 25, 2026

Last Verified

August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LLB-2017-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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