Clinical Trials Register

Summary
EudraCT Number:	2010-023271-26
Sponsor's Protocol Code Number:	MI-CI-C02
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-12-20
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2010-023271-26

A.3

Full title of the trial

A randomized, double-blind, multi-centre, placebo controlled phase II clinical study to evaluate the efficacy, tolerance and 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)

A.3.2

Name or abbreviated title of the trial where available

Colvir-Phase II

A.4.1

Sponsor's protocol code number

MI-CI-C02

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Mithra Pharmaceuticals SA
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	2% (w/w) cidofovir gel
D.3.2	Product code	CID
D.3.4	Pharmaceutical form	Vaginal gel
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Vaginal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CIDOFOVIR
D.3.9.1	CAS number	113852-37-2
D.3.9.3	Other descriptive name	(S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine
D.3.10	Strength
D.3.10.1	Concentration unit	% (W/W) percent weight/weight
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Vaginal gel
D.8.4	Route of administration of the placebo	Vaginal use

E. General Information on the Trial

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

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

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

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.2.1	Number of subjects for this age range:	132
F.1.3	Elderly (>=65 years)	No
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	No
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	200

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-02-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-01-25

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-02-26

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