Clinical Trials Register

Summary
EudraCT Number:	2015-004563-37
Sponsor's Protocol Code Number:	IPR_GARDEFLORA_15-2
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2016-04-01
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2015-004563-37

A.3

Full title of the trial

Study of the efficacy and safety of treatment with completely lyophilised
cultures of Lactobacillus crispatus - IP 174178 administered intravaginally
in the treatment of bacterial vaginosis.

Badanie skuteczności i bezpieczeństwa leczenia pełną liofilizowaną kulturą Lactobacillus crispatus – IP 174178 podawaną dopochwowo w leczeniu waginozy bakteryjnej, pod nazwą IPR_GARDEFLORA_15-2

A.3.1

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

Study of the efficacy and safety of treatment administered intravaginally
in the treatment of bacterial vaginosis.

Badanie skuteczności i bezpieczeństwa leku podawanego dopochwowo w leczeniu
waginozy bakteryjnej

A.3.2

Name or abbreviated title of the trial where available

IPR_GARDEFLORA_15-2

A.4.1

Sponsor's protocol code number

IPR_GARDEFLORA_15-2

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	Laboratoires IPRAD PHARMA
B.1.3.4	Country	France
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	Laboratoires IPRAD-PHARMA
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	ITEC Services
B.5.2	Functional name of contact point	Nathalie CIENCIEWIEZ
B.5.3	Address:
B.5.3.1	Street Address	3 avenue Georges Clémenceau
B.5.3.2	Town/ city	CENON
B.5.3.3	Post code	33150
B.5.3.4	Country	France
B.5.4	Telephone number	330557778500
B.5.5	Fax number	330557778501
B.5.6	E-mail	nathalie.cienciewiez@itecservices.com

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	Lactobacillus crispatus
D.3.2	Product code	IP174 178
D.3.4	Pharmaceutical form	Vaginal capsule
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	Lactobacillus Crispatus IP174178
D.3.9.1	CAS number	D007778000
D.3.9.2	Current sponsor code	IP174178
D.3.9.3	Other descriptive name	LACTOBACILLUS
D.3.9.4	EV Substance Code	SUB43635
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	347
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)	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	FLAGYL 250mg
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI-AVENTIS France
D.2.1.2	Country which granted the Marketing Authorisation	France
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	Metronidazole
D.3.4	Pharmaceutical form	Tablet
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	METRONIDAZOLE
D.3.9.1	CAS number	443-48-1
D.3.9.3	Other descriptive name	2-methyl-5-nitro-1H-imidazole-1-ethanol
D.3.9.4	EV Substance Code	SUB08922MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	225 to 275
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Vaginal capsule
D.8.4	Route of administration of the placebo	Vaginal use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
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

Bacterial vaginosis

Waginoza bakteryjna

E.1.1.1

Medical condition in easily understood language

Bacterial vaginosis

Waginoza bakteryjna

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	LLT
E.1.2	Classification code	10046960
E.1.2	Term	Vaginosis bacterial
E.1.2	System Organ Class	100000004862

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assess the efficacy of Lactobacillus crispatus – IP174178 in the normalisation of AMSEL criteria on D14 in the 2 arms.

Ocena skuteczności Lactobacillus crispatus – IP174178 w normalizacji kryteriów AMSELA w 14-tym dniu badania (D14) w 2 ramionach.

E.2.2

Secondary objectives of the trial

Assess the efficacy of Lactobacillus crispatus – IP174178 in the normalisation of AMSEL criteria on D28 in the 2 arms.
Assess the efficacy of Lactobacillus crispatus – IP174178 in the normalisation of AMSEL criteria on D14 in the 2 arms, in 3
subpopulations.
Assess the efficacy of Lactobacillus crispatus – IP174178 in the normalisation of AMSEL criteria on D28 in the 2 arms, in 3
subpopulations.
Assessment of clinical response by the normalisation of AMSEL criteria AND bacteriological response (Nugent ≤ 3) on D14 and D28 globally and
in three subpopulations.
Assessment of bacteriological response (Nugent ≤ 3) on D14 and D28 globally and in three subpopulations.
Evaluate the safety of Lactobacillus crispatus – IP174178 and compare it to standard treatment.

• Ocena skuteczności Lactobacillus crispatus – IP174178 w normalizacji kryteriów AMSELA w D28 w 2 ramionach.
• Ocena skuteczności Lactobacillus crispatus – IP174178 w normalizacji kryteriów AMSELA w D14 w 2 ramionach, w 3 podgrupach.
• Ocena skuteczności Lactobacillus crispatus – IP174178 w normalizacji kryteriów AMSELA w D28 w 2 ramionach, w 3 podgrupach.
• Ocena odpowiedzi klinicznej poprzez normalizację kryteriów AMSELA oraz odpowiedź bakteriologiczną (wynik w skali Nugenta ≤ 3) w D14 i D28 globalnie i w trzech podgrupach.
• Ocena odpowiedzi bakteriologicznej (wynik w skali Nugenta ≤ 3) w D14 i D28 globalnie i w trzech podgrupach.
• Ocena tolerancji Lactobacillus crispatus – IP174178 i porównanie jej z tolerancją leczenia referencyjnego.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Woman over 18 years old,
• Patients with clinical symptoms suggestive of bacterial vaginosis, linked to an imbalance of vaginal flora, characterised by the presence of at least 3 of 4 of the following Amsel clinical criteria: uniform greyish vaginal discharge, characteristic odour of "rotten fish" caused by the spontaneous release of amine or during the potassium test or "sniff test", vaginal pH greater than 4.5, presence of "clue cells" (at least 20%) during the vaginal secretions direct exam
• Patient with negative pregnancy test at V1,
• Patient using a contraceptive method considered effective by the investigator (excluding spermicides),
• Patient having received all the information on the study and having voluntarily given her written informed consent,
• Patient registered with social security or other social protection.

E.4

Principal exclusion criteria

• Presence of an existing gynaecological infection that may affect the evaluation of the trial treatment (severe dysplasia or cervical carcinoma in situ, invasive carcinoma, cervical intraepithelial neoplasia, squamous intraepithelial lesions etc.),
• Patient having taken an antibiotic or antifungal treatment within 14 days prior to V1 (after administration by any route).
• Patient unable to comply with the constraints of the protocol,
• Patients having more than 12 days of menses per month,
• Patient pregnant or breastfeeding,
• Menopausal patient,
• Patient with a known allergy to any of the active substances or to any of the excipients of the study products,
• Patient with severe acute or chronic disease considered by the investigator as being incompatible with participation in this study, or with a serious infection that may endanger the life of the patient in the short term,
• Immunosuppressed patient,
• Patient with a previous illness that, according to the investigator, could compromise the results of the study or expose the patient to additional risk,
• Patient with psychological or linguistic factors limiting the understanding and signature for the informed consent form,
• Patient deprived of their liberty by court judgement or subject to guardianship,
• Patient at risk of failing to follow the treatment (compliance problem),
• Patient impossible to contact in an emergency.
• Antibiotics or fungicides taken systemically during the month preceding the screening visit, excluding treatments for the bacterial vaginosis episode.
• Use of local probiotics in the months preceding the screening visit.
• Use of antiseptics in the months preceding the screening visit, excluding treatments for the bacterial vaginosis episode.
• Use of prebiotics (acidifiers) during the two weeks preceding the screening visit.
• Use of products containing topical oestrogen in the month before the screening visit.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with normalisation of AMSEL criteria at D14 in the 2 arms.

E.5.1.1

Timepoint(s) of evaluation of this end point

Proportion of patients with normalisation of AMSEL criteria at D14 in the 2 arms.

E.5.2

Secondary end point(s)

Proportion of patients with normalisation of AMSEL criteria at D28 in the 2 arms.
Proportion of patients with normalisation of AMSEL criteria at D14 in the 2 arms in the 3 populations.
Proportion of patients with normalisation of AMSEL criteria at D28 in the 2 arms in the 3 subpopulations.
Assessment of clinical response by the normalisation of AMSEL criteria AND bacteriological response (Nugent ≤ 3) on D14 and D28 globally and in the three subpopulations.
Assessment of bacteriological response (Nugent ≤ 3) on D14 and D28 globally and in the three subpopulations.
Adverse events: Adverse events occurring during the study, as noted by the patient in her self-assessment log (diary) or gathered by the Investigator during visits, will be recorded in the Case Report Form (e-CRF).
Evaluation of overall tolerance by the Investigator, after questioning the patient.
This evaluation will be carried out using the following grading scheme:
1 = Very good tolerance: no functional sign of discomfort and no objective signs on examination.
2 = Good tolerance: a few functional signs of discomfort but minimum and short-lived in nature, not causing temporary cessation of
applications. No objective signs on examination.
3 = Moderate tolerance: marked or persistent functional signs of discomfort or objective signs on examination but not causing application
of the trial product to cease temporarily.
4 = Poor tolerance: functional and/or objective signs leading the patient to stop using the trial product.

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepoints already indicated in the "secondary end point(s)" part (E.5.2).

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

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)

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

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)

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

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

Yes

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 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:

530

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

320

F.4.2

For a multinational trial

F.4.2.1

In the EEA

530

F.4.2.2

In the whole clinical trial

530

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

Non applicable

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

2016-12-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2017-05-29

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