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

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.

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.

Study Overview

• Status: Completed
• Conditions: Cervix Intraepithelial Neoplasia; Uterine Cervical Neoplasia
• Intervention / Treatment: Drug: C1

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Bruxelles, Belgium, 1070
    • Hôpital Erasme
  • Bruxelles, Belgium, 1020
    • CHU Brugmann
  • Bruxelles, Belgium, 1000
    • Hôpital Saint Pierre
  • Charleroi, Belgium, 6000
    • CHU Charleroi Hôpital Civil
  • La Louvière, Belgium, 7100
    • CHU Tivoli
  • Liege, Belgium, 4000
    • CHR Citadelle
  • Bruxelles
    • Ixelles, Bruxelles, Belgium, 1050
      • HIS Ixelles
  • Charleroi
    • Montigny-le-Tilleul, Charleroi, Belgium, 6110
      • CHU Charleroi Site André Vésale
  • Liege
    • Chenee, Liege, Belgium, 4032
      • CHU ND des Bruyères

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo group	Drug: C1; Local application of the experimental gel or placebo gel.
EXPERIMENTAL: Treatment group	Drug: C1; Local application of the experimental gel or placebo gel.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Mithra Pharmaceuticals
• Investigators: Principal Investigator: Philippe SIMON, MD, PhD, Professor, Hôpital Erasme, service de gynécologie obstétrique

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (ACTUAL): February 1, 2013
• Study Completion (ACTUAL): February 1, 2013

Study Registration Dates

• First Submitted: February 18, 2011
• First Submitted That Met QC Criteria: February 23, 2011
• First Posted (ESTIMATE): February 24, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): February 18, 2013
• Last Update Submitted That Met QC Criteria: February 15, 2013
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Carcinoma in Situ; Neoplasms; Cervical Intraepithelial Neoplasia
• Other Study ID Numbers: MI-CI-C02; 2010-023271-26 (EUDRACT_NUMBER)