Clinical Trials Register

Summary
EudraCT Number:	2015-001472-22
Sponsor's Protocol Code Number:	IMUNOR-201501
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-08-03
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

Czechia - SUKL

A.2

EudraCT number

2015-001472-22

A.3

Full title of the trial

A Prospective, Randomized, Double-Blind, Placebo-controlled, Multicenter, Phase III Study Assessing Efficacy and Safety of the IMUNOR® Therapy Versus Placebo in Patients with Recurrent Vulvovaginitis Episodes

Prospektivní, randomizovaná, dvojitě-zaslepená, placebem kontrolovaná, multicentrická studie fáze III, hodnotící účinnost a bezpečnost léčby IMUNOR®-em, v porovnání s placebem, u pacientek s opakovanými epizodami vulvovaginitidy

A.3.1

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

IMUNOR® Therapy Versus Placebo in Patients with Recurrent Vulvovaginitis Episodes

Léčba IMUNOR®-em, v porovnání s placebem, u pacientek s opakovanými epizodami vulvovaginitidy

A.3.2

Name or abbreviated title of the trial where available

IMUNOR-201501

A.4.1

Sponsor's protocol code number

IMUNOR-201501

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	ImunomedicA, a.s.
B.1.3.4	Country	Czechia
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	ImunomedicA, a.s.
B.4.2	Country	Czechia
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ImunomedicA, a.s.
B.5.2	Functional name of contact point	Ing. Zdeňka Svobodová
B.5.3	Address:
B.5.3.1	Street Address	Chuderov 118
B.5.3.2	Town/ city	Ústí nad Labem
B.5.3.3	Post code	40002
B.5.3.4	Country	Czechia
B.5.4	Telephone number	00420777872 067
B.5.5	Fax number	00420472776623
B.5.6	E-mail	imunomedica@iol.cz

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	Imunor
D.2.1.1.2	Name of the Marketing Authorisation holder	ImunomedicA, a.s.
D.2.1.2	Country which granted the Marketing Authorisation	Czechia
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	Imunor
D.3.4	Pharmaceutical form	Oral lyophilisate
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	Transferendi factor suillus 10 mg
D.3.9.1	CAS number	8000043-00-7
D.3.9.3	Other descriptive name	TRANSFER FACTOR
D.3.9.4	EV Substance Code	SUB15595MIG
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	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	Yes
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	Oral lyophilisate
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Recurrent vulvovaginitis episodes

Opakované epizody vulvovaginitidy

E.1.1.1

Medical condition in easily understood language

Recurrent vulvovaginitis episodes

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	PT
E.1.2	Classification code	10047794
E.1.2	Term	Vulvovaginitis
E.1.2	System Organ Class	10021881 - Infections and infestations

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 confirm efficacy of IMUNOR® based on reduction of the number of mycotic and bacterial vulvovaginitis episodes during 12 months observation, compared to patients receiving placebo.

E.2.2

Secondary objectives of the trial

• To confirm efficacy of IMUNOR® based on reduction of the number of mycotic vulvovaginitis episodes during 6 months observation, as compared to placebo;
• To compare the mean duration of mycotic vulvovaginitis episodes;
• Comparison of the proportion of patients withdrawn from the study due to the need of use of oral antifungal medication;
• To evaluate safety of the IMUNOR® treatment based on the assessment occurrence of adverse events and monitored laboratory parameters;
• To compare the use of local symptomatic and/or topical antifungal treatment;
• To assess the quality of life of patients;
• To evaluate changes in vaginal biocenosis;
• To evaluate basic pharmacoeconomics parameters.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

By inclusion into the Study, patients from participating centers will be offered the possibility to take part in a sub-study evaluating changes in selected immunological parameters occurring during IMP administration. At Visit 1, patients willing to take part will be asked to sign an additional informed consent form for their participation in the sub-study. Within the sub-study, at Visits 1, 3 and 5, additional blood samples will be taken for an immunological examination (CD3, CD4, CD8, CD16/56, phagocyte activity, total IgM, IgA, IgG and specific anti-D-mannan IgM and anti-D-glucan IgG antibodies).

E.3

Principal inclusion criteria

1.Females aged 18 - 50 years, without signs of menopause-related estrogen deficiency;
2.Suspected secondary immune deficiency based on presence of recurrent, symptomatic mycotic and/or bacterial vulvovaginitis episodes documented by a gynecologist (4 or more episodes during the last 12 months prior randomization, with the exception of mycotic episodes accompanying systemic administration of antibiotics);
3.Patients willing and able to sign the informed consent, cooperate and participate on prescribed study visits;
4.Stable sexual relationships 12 months prior signature of the informed consent and a prerequisite for maintaining them for the next 12 months;
5.Documented use of an effective contraception method, Pearl index ≤ 1.

E.4

Principal exclusion criteria

1.Subjects with known hypersensitivity to any ingredient of the study medication;
2.Pregnant or breast feeding females;
3.Females planning to get pregnant during the course of the next 12 months;
4.Known personal history of hypothyreosis (or suspected);
5.Known personal history of elevated anti-thyroidal antibodies;
6.Known personal history of an autoimmune or malignant disease;
7.Known personal history of HIV positivity, tuberculosis or intake of treatment lowering the function(s) of the immune system (e.g. immunosuppresants, chemotherapy), with the exception of treatment of bronchial asthma, or allergies (nasal or inhaled corticosteroids);
8.Known personal history of HIV positivity, tuberculosis or intake of treatment lowering the function(s) of the immune system (e.g. immunosuppresants, chemotherapy), with the exception of treatment of bronchial asthma, or allergies (nasal or inhaled corticosteroids);
9.Acute vulvovaginitis with presence of herpetic viruses or gonorrhea;
10.Evidence of chlamydia, trichomonads or an other sexually transmitted disease within 30 days prior the first study visit;
11.Use of immune modulation therapy (transfer factor, bacterial lysates, systemic enzymatic therapy, immunoglobulins) during the last 12 months prior the first study visit, or planned initiation of such treatment during the course of the study;
12.Use of vaginal probiotics, or antibiotics (systemic), completed less than 30 days prior the first study visit;
13.Participation in another clinical trial within 30 days prior the first study visit;
14.Any clinically significant condition or disease, which in the opinion of the investigator, could affect safety of the patient or evaluation of this Study.

E.5 End points

E.5.1

Primary end point(s)

Assessment of IMUNOR®`s efficacy based on reduction of the number of vulvovaginitis episodes, with confirmed mycotic or bacterial etiology, during 12 months observation time, compared to patients receiving placebo. Episodes starting prior the first IMP administration will be documented, but not used for the analysis. All episodes starting during the second Observation Phase and being, or not, resolved after Visit 6 will be included into the analysis. If the patient terminates the Study prematurely then the number of vulvovaginitis episodes will be increased by one (1) episode.

E.5.1.1

Timepoint(s) of evaluation of this end point

During the statistical analysis after the last visit of the last patient.

E.5.2

Secondary end point(s)

•Confirmation of IMUNOR®`s efficacy based on reduction of the number of vulvovaginitis episodes, with confirmed mycotic or bacterial etiology, during the initial 6 months observation time, compared to patients receiving placebo. Episodes starting prior the first IMP administration will be documented, but not used for the analysis. All episodes starting during the first Observation Phase and being, or not, resolved after Visit 4 will be included into the analysis;
•Comparison of the mean duration of all documented mycotic or bacterial vulvovaginitis episodes in patients receiving IMUNOR® or placebo. The analysis will be separately performed for the 6- and 12-months observation time as well as for vulvovaginitis episodes with bacterial and mycotic etiology;
•Evaluation of safety of the IMUNOR® treatment based on:
-occurrence of adverse events,
-assessment of monitored laboratory parameters:

Explorative Endpoint
Analysis of selected immunological parameters in patients participating in the immunology sub-study - CD3, CD4, CD8, CD16/56, CD19, HLA-DR, phagocyte activity, total IgM, IgA, IgG and specific anti-D-mannan IgM and anti-D-glucan IgG antibodies. Values at the end of each IMP administration period will be compared with the baseline (Visit 1) and among both treatment groups.

oHematology (hemoglobin, hematocrit, MCV, MCH, MCHC, RDW, total and differential leukocyte count, red blood cell count, platelet count, PDW),
oSerum chemistry (glucose, total proteins, serum albumin, urea, serum creatinine, AST, ALT, total bilirubine, direct bilirubine, sodium, potassium, CRP),
oUrine cultivation;
•Assessment of the use of local symptomatic and/or topical antifungal or antibacterial treatment and its comparison among both treatment groups as well as between both IMP administration + observation cycles (1 cycle = 3-months IMP administration + 3-months observation);
•Assessment of IMUNOR®`s efficacy based on reduction of the number of vulvovaginitis episodes, in patients with prevailing bacterial etiology (within 12 months prior Screening), during 12 months observation time, compared to patients receiving placebo. Episodes starting prior the first IMP administration will be documented, but not used for the analysis. All episodes starting during the second Observation Phase and being, or not, resolved after Visit 6 will be included into the analysis. If the patient terminates the Study prematurely then the number of vulvovaginitis episodes will be increased by one (1) episode;
•Assessment of IMUNOR®`s efficacy based on reduction of the number of vulvovaginitis episodes, in patients with prevailing mycotic etiology (within 12 months prior Screening), during 12 months observation time, compared to patients receiving placebo. Episodes starting prior the first IMP administration will be documented, but not used for the analysis. All episodes starting during the second Observation Phase and being, or not, resolved after Visit 6 will be included into the analysis. If the patient terminates the Study prematurely then the number of vulvovaginitis episodes will be increased by one (1) episode;
•Analysis of the proportion of patients withdrawn from the Study due to the need of oral antifungal medication administration and their comparison between both treatment groups;
•Assessment of the Quality of Life based on 2 provided questionnaires and its comparison among both treatment groups;
•Evaluation of vaginal biocenosis changes and its comparison among both treatment arms. The following parameters will be evaluated:
oPresence of normal vaginal flora,
oPresence of vaginal pathogens confirmed by cultivation.
A comparison among both treatment groups will be done at baseline, after 6 and 12 months observation time (or after premature study withdrawal);
•Evaluation of basic pharmacoeconomic parameters (will be done by the pharmacoecnomist).

E.5.2.1

Timepoint(s) of evaluation of this end point

During the statistical analysis after the last visit of the last patient.

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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

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

Yes

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

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:

135

F.1.3

Elderly (>=65 years)

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

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

105

F.4.2

For a multinational trial

F.4.2.1

In the EEA

135

F.4.2.2

In the whole clinical trial

135

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)

Routine medical care

Běžná zdravotní starostlivost

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

2015-07-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-06-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-04-08

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