Clinical Trials Register

Summary
EudraCT Number:	2020-000758-81
Sponsor's Protocol Code Number:	Chlorhex-KKDS-2021
National Competent Authority:	Sweden - MPA
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-10-29
Trial 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

Sweden - MPA

A.2

EudraCT number

2020-000758-81

A.3

Full title of the trial

Chlorhexidine gluconate as treatment and prophylaxis of vulvovaginal Candidiasis

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A clinical trial for Chlorhexidine as treatment for vulvovaginal candidiasis

A.3.2

Name or abbreviated title of the trial where available

Chlorhex-KKDS-2021

A.4.1

Sponsor's protocol code number

Chlorhex-KKDS-2021

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	Karolinska Institutet
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	ALF Swedish Research Council funding for clinical research in medicine
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Danderyd Hospital
B.5.2	Functional name of contact point	Div of Obstetrics and Gynecology
B.5.3	Address:
B.5.3.1	Street Address	Danderyd Hospital
B.5.3.2	Town/ city	Stockholm
B.5.3.3	Post code	18288
B.5.3.4	Country	Sweden
B.5.4	Telephone number	+46812355000

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	Yes
D.2.1.1.1	Trade name	Hibitane
D.2.1.1.2	Name of the Marketing Authorisation holder	Bioglan
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	Hibitane
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Vaginal cream
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	CHLORHEXIDINE GLUCONATE
D.3.9.3	Other descriptive name	Hibitane vaginal cream
D.3.9.4	EV Substance Code	SUB01215MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Yes
D.2.1.1.1	Trade name	Fluconazol
D.2.1.1.2	Name of the Marketing Authorisation holder	Accord
D.2.1.2	Country which granted the Marketing Authorisation	Sweden
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	Fluconazole
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Fluconazole
D.3.9.3	Other descriptive name	FLUCONAZOLE
D.3.9.4	EV Substance Code	SUB07674MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
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	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Candida vulvovaginitis

E.1.1.1

Medical condition in easily understood language

Vaginal yeast infection

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

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 analyze if daily vaginal application of 8 ml of Hibitane® for one week and thereafter once a week for another 11 consecutive weeks is at least as effective as fluconazole 150 mg capsules every third day for the first three doses and thereafter 150 mg once a week for another 11 consecutive weeks regarding treatment- and prophylactic efficacy for recurrent vulvovaginal Candida albicans infection.

E.2.2

Secondary objectives of the trial

1. To analyze adverse events
2. To analyzed clinical symptoms and findings
3. To study the effect on vaginal microbiome of lactobacillus before and after treatment and prophylaxis with CHG for RVVC.
4. To evaluate the event of relapses during and after the prophylaxis treatment
5. To investigate if CHG has toxic effect on the vaginal epithelial cells.
6. To analyze vaginal biofilm formation before and after treatment and prophylaxis with CHG and FLZ for RVVC.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• 18-50 years of age
• A history of > 2 candida infections the last year
• Symptoms of acute vulvovaginal candida infection
• Culture verified infection with Candida albicans
• Adequate contraceptive method
• Able to understand oral and written information in Swedish
• The subject has given written consent to participate in the study

E.4

Principal exclusion criteria

• Severe somatic or mental illness (including liver and kidney failure and cardiac disease)
• Immunosuppressive medication
• Pregnancy
• Lactation
• Other ongoing gynecological infections
• Allergy to fluconazole or chlorhexidine gluconate
• Citalopram or other medication that might have impact on the QT interval (terfenadin, cisaprid, astemizol, pimozid, kinidin, erythromycin, halofantrin, amiodaron)
• Participation or recent participation (30 days) in a clinical study with an investigational product. Previous participation in this study.

E.5 End points

E.5.1

Primary end point(s)

The proportion of women in each group that has negative vaginal cultures for Candida albicans 1 week after active treatment.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 week (+2 days) after completed treatment. Control of AE, culture for Candida albicans and examination

E.5.2

Secondary end point(s)

1. The proportion of women in each group that has negative vaginal cultures for Candida albicans at 3 months’ follow-up after prophylactic treatment and at 6 months’ follow-up after the observational phase of the study.
2. Analysis of proportion of women with adverse events (AE) across treatment arms. The AEs will also be reported in descriptive terms and summarized for each treatment arm.
3. Proportion of women with symptom score > 2. Each symptom of typical discharge, itching, dryness of the skin/mucosa, burning and pain will generate 1 point of a composite index (range 0-5).
4. Proportion of women with examination score >2. Each finding of redness skin/mucosa, typical discharge, dry skin/mucosa, fissures skin/mucosa, visible candida hyphae in the microscope will generate 1 point of a composite index (range 0-5).
5. Proportion of women with reduced vaginal lactobacilli content in vaginal smears measured by a semi-quantitative method as normal or reduced quantity.
6. Proportion of women with relapse of Candida albicans infection between end of treatment and end of prophylactic treatment (1week post treatment to 3 months’ follow-up) and between 3- and 6 months’ follow-up after end of prophylactic treatment.
7. Proportion of women with possible toxic effect on the vaginal epithelium, defined as disruption and/or inflammation of the epithelial lining, analyzed from vaginal biopsies before and after treatment and prophylaxis.
8. Further analysis of mucosa inflammatory mechanism (histopathology and immunohistochemistry) and biofilm formation during and after treatment and prophylaxis, analyzed from vaginal biopsies. The methods for these in vitro exploratory analyses are not yet decided on.

E.5.2.1

Timepoint(s) of evaluation of this end point

Visit 3 1 week (+2 days) after completed treatment. Control of AE, culture for Candida albicans and examination (no biopsies). 30 min.
Visit 4 After 12 weeks (+ 1 week) from inclusion when prophylactic treatment is completed. Control of AE and relapses, culture for Candida albicans and examination, vaginal biopsies. 45 min.
Visit 5 Follow-up 6 months (+ 1-2 weeks) from baseline/inclusion. Control of AE and relapses, culture for Candida albicans and examination (no biopsies). End of study. 30 min.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

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

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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)

Yes

E.8.2.2

Placebo

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

Yes

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

LVLS

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-10-29.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

none

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2021-04-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-08

P. End of Trial
P.	End of Trial Status	Ongoing

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