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

Study Overview
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Brief Summary
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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.

Detailed Description
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The study duration will be 48 months with 36 months of inclusion (that may be extended if the expected number of patients is not reached after 36 months) and 12 months of follow-up. Patients aged between 25 and 45 years who present cervical abnormalities 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, Normal cytology, Safety. 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.

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

Conditions
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Human Papilloma Virus

Intervention / Treatment
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* Drug: 2LPAPI®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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 CIN I, and current cytology presenting ASC-US, AGUS, LSIL, ASC-H, AGC or LSIL+ASC-H or current diagnosis of CIN I at the cervical smear, 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 cervical smear, 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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2LPAPI® arm<br>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®<br>* Treatment<br>* Other names: 2LPAPI;|
| Placebo Comparator: Placebo arm<br>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<br>* Placebo<br>|

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Normal cytology | The objective of this outcome will be to compare the number of patients with normal cytology at 6-month and 12-month visits. | 6 and 12 months | 
| Occurrence of adverse events (AEs) and severe adverse events (SAEs), considered as related or not to the study drug |  | 6 months |