Safety and Efficacy Study of Antiviral Local Application to Treat High Grade Cervical Intraepithelial Lesions (CIN2/3)

Study Overview
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Brief Summary
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The purpose of this phase-II study is to evaluate the efficacy and safety of an aqueous gel containing an antiviral, administered directly on cervix exhibiting high grade squamous or glandular intraepithelial lesion (CIN 2 and 3) in comparison with a placebo treatment.

Detailed Description
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Human Papilloma Virus (HPV) infections induce cervical intraepithelial neoplasia (CIN) of cervix. To reduce incidence of invasive tumor associated with high grade CIN lesions, the standard treatment is the conisation of cervix (surgical act). A local treatment with antiviral would preserve the cervix of young subjects and reduce obstetrical morbidity induced by the conisation. This clinical study is aimed at: to evaluate the efficacy of a gel with antiviral directly applied on the cervix exhibiting high grade CIN lesions (CIN2/3): conisation is still indicated? to evaluate the safety and tolerance after local application.

Official Title
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A Randomized, Double-blind, Multi-centre, Placebo Controlled Phase II Clinical Study to Evaluate the Efficacy, Tolerance and Safety of an Aqueous Gel Containing an Antiviral, Directly Applied on the Cervix Exhibiting High Grade Intraepithelial Lesion.

Conditions
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Uterine Cervical Neoplasia, Cervix Intraepithelial Neoplasia

Intervention / Treatment
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* Drug: C1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women aged between 18 and 50 years old Informed consent signed Cervical lesion classified CIN 2 or 3, on a biopsy made during the 60 days before inclusion No sexual activity, or proved sterility, or use of effective mechanical, hormonal or intrauterine contraception during 30 days following inclusion (except vaginal ring Nuvaring, diaphragm and spermicide) Exclusion Criteria: Invasive or microinvasive cervical neoplasia Pregnancy or breast feeding Subtotal hysterectomy Current renal impairment Current immune disorder including serology HIV + Current use of drugs interfering with renal function Current use of oncologic treatment Current use of immune treatment Current use of anti-viral treatment Current vaginal application of drugs or cosmetics Prior treatment with the antiviral on the cervix Local or general condition incompatible with the experimental treatment in the opinion of the principal investigator Current or recent participation to another experimental study during the last 3 months before the screening visit

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Treatment group<br> | Drug: C1<br>* Local application of the experimental gel or placebo gel.<br>|
| Placebo Comparator: Placebo group<br> | Drug: C1<br>* Local application of the experimental gel or placebo gel.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy at week 12: change of histological and cytological parameters (success or not) | Efficacy will be measured by histological and cytological criteria at week 12 (disappearance of CIN 2+) in correlation with viral status (positive or negative) before and after treatment. | 12 weeks | 
| Efficacy at week 28: recurrence rate | The recurrence rate will be assessed at week 28, by the same histological and cytological criteria in correlation with the viral status (positive or negative) before and after treatment. | 28 weeks | 
| Tolerance and Safety (AE reporting, changes of gynecological and biological parameters) | Safety will be measured by record of adverse events, changes in clinical biology test results; local tolerance will be measured by patient questioning and gynecological examination of vagina and cervix. | during 30 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Virological status (infection) | The viral load and genotypes of HPVhr will be determined before treatment, during follow-up and at the end of the study, by using a quantitative analysis. | during 30 weeks | 
| Changes in lesion (colposcopic changes) | Colposcopic description of lesion will be done before, during and after treatment of the lesion, during follow up and at the end of the study. | during 30 weeks |