E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High Grade of Cervical Intraepithelial Neoplasia (CIN). |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007494 |
E.1.2 | Term | Carcinoma uterine cervix in situ |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy and the safety of an aqueous gel containing 2 % (w/w) of cidofovir, directly applied on the cervix exhibiting high grade intraepithelial lesion(s) (CIN 2 and 3). |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the colopsocopic and the virological changes after the local application of the aqueous gel containing
2 % (w/w) of cidofovir, directly on the cervix exhibiting high grade intraepithelial lesion(s) (CIN 2 and 3). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 preceding days;
-no sexual activity or proved sterility or use of effective mechanical, hormonal or intrauterine contraception (except vaginal ring Nuvaring, diaphragm and spermicide). |
|
E.4 | Principal exclusion criteria |
-invasive or microinvasive cervical neoplasia;
-pregnancy or breast feeding;
-subtotal hysterectomy;
-current renal impairment;
-current immune disorder including serology HIV+;
-current systemic use of drugs interfering with renal function (intravenous contrast media, aminoglycosides, glycopeptides)
-current systemic treatment for any cancer;
-current systemic use of treatment interfering with immunity (table 2), except vaccines;
-current systemic use of anti-viral treatment (table 2)
-current vaginal application of drugs or cosmetics;
-previous topical treatment of the cervix by cidofovir;
-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. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint of efficacy will be mean change of histological and cytological parameters in each treatment group (cidofovir vs placebo) and the comparison between them
-At week 12, the success, partial success and failure rates in term of histological and cytological signs of disappearance of the CIN2+ lesion will be evaluated in each group. Abnormal cytological results are considered only if HPVhr are present in the sample.
-At week 28 (study end), the recurrence rate of CIN 1 and CIN 2/3 will be measured in the population of partial and complete success at week 12 (population who continue in the study), according the same criteria as at week 12.
The primary endpoints of safety and local tolerance will be:
-the adverse events reporting;
-the absence of renal impairment (blood creatinine level);
-the absence of inflammation markers in plasma (CRP, differential leukocyte count);
-the local tolerance (local symptoms and gynecological examination). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Efficacy: 12 and 28 weeks
Safety: each day during the protocol. |
|
E.5.2 | Secondary end point(s) |
The viral load and genotypes of HPVhr will be determined before treatment.
Colposcopic : colposcopic change at the study end will be classified as: “progression, unchanged, partial regression, or total regression”. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Virology: at weeks 4 and 12, and at the end of the study (week 28).
Coloposcopy: before, during and after treatment of the lesion, during follow up and at the end of the study.
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
It will be the last visit of the last subject undergoing the trial. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |