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

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.

The KCE Report 238Cs (2015) recommends " HR-HPV-positive women should not be offered colposcopy immediately. Triage should be done using cytology for this purpose. If cytological abnormalities (ASCUS+) are found, immediate referral should follow for diagnosis and, where appropriate, treatment. If no abnormalities are observed in triage, the subject should be offered follow-up testing (cytology) at six 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: Human Papilloma Virus
• Intervention / Treatment: Drug: Placebo; Drug: 2LPAPI®

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

• Study Contact: Name: Laura FERTE; Phone Number: +32499717964; Email: laura.ferte@labolife.com
• Study Contact Backup: Name: Charlotte BOLLE; Email: charlotte.bolle@labolife.com

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
  • Bruxelles, 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
  • Bruxelles, Belgium, 1050
    • Recruiting
    • Hôpitaux Iris Sud - Iris Zuid Ziekenhuis
    • Principal Investigator: Frédéric Buxant, MD
    • Sub-Investigator: Fiona Avau, MD
    • Contact: Frédéric BUXANT, MD
  • Bruxelles, 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
  • Charleroi, Belgium, 6042
    • Active, not recruiting
    • Hôpital Civil Marie Curie ISPPC
  • Malmédy, 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
    • Recruiting
    • UCL Namur - site Sainte Elisabeth
    • Principal Investigator: Benoit MOONS
    • Sub-Investigator: Sarah MITRI
    • Contact: MD
    • Contact: Benoit MOONS; Email: benoit.moons@chuuclnamur.uclouvain.be
  • Namur, Belgium, 5000
    • Active, not recruiting
    • 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

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

2

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.	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		6 months
Comparison of 2LPAPI® versus placebo on HR-HPV infection clearance rate at 6-month visits.	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.	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.	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.	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

• Sponsor: Labo'Life

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2020
• Primary Completion (Estimated): March 15, 2027
• Study Completion (Estimated): October 30, 2027

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): October 31, 2024
• Last Update Submitted That Met QC Criteria: October 29, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Neoplasms; Disease Attributes; Infections; Virus Diseases; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; DNA Virus Infections; Neoplasms, Squamous Cell; Tumor Virus Infections; Papillomavirus Infections; Papilloma
• Other Study ID Numbers: LLB-2017-01

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