Clinical Trials Register

Summary
EudraCT Number:	2011-003089-34
Sponsor's Protocol Code Number:	HND-IM-011
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-07-28
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

Germany - PEI

A.2

EudraCT number

2011-003089-34

A.3

Full title of the trial

The effect for Lactobacillus paracasei subsp. paracasei, L. casei 431® on immune response to influenza vaccination in healthy adult volunteers - a multi-center, randomized, placebo-controlled, parallel-group study with six weeks intervention

A.3.1

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

The effect of a diary product with a probiotic on immune response to influenza vaccination in healthy adult volunteers - a multi-center, randomized, placebo-controlled, parallel-group study with six weeks intervention

A.4.1

Sponsor's protocol code number

HND-IM-011

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	Chr. Hansen A/S
B.1.3.4	Country	Denmark
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	Chr. Hansen A/S
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Chr. Hansen A/S
B.5.2	Functional name of contact point	dkcmm@chr-hansen.com
B.5.3	Address:
B.5.3.1	Street Address	Bøge Allé 10-12
B.5.3.2	Town/ city	Hørsholm
B.5.3.3	Post code	2970
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+4545748562
B.5.5	Fax number	+4550926137
B.5.6	E-mail	dkcmm@chr-hansen.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	Yes
D.2.1.1.1	Trade name	Influvac 2011/2012
D.2.1.1.2	Name of the Marketing Authorisation holder	Abbott Biologicals B.V.
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	Influvac
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
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	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	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.2.1.1.1	Trade name	Lactobacillus paracasei subsp. paracasei, L.casei 431
D.2.1.1.2	Name of the Marketing Authorisation holder	Chr. Hansen A/S
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
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)	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	Yes
D.3.11.13.1	Other medicinal product type	probiotics

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
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

effect of probiotics on the immune response to seasonal influenza vaccination in healthy adults

E.1.1.1

Medical condition in easily understood language

effect of an acidified milk product containing bacteria on the immune response to seasonal influenza vaccination in healthy adults

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	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10016794
E.1.2	Term	Flu vaccination
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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	10036897
E.1.2	Term	Prophylactic vaccination
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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	10046859
E.1.2	Term	Vaccination
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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 investigate the effect of probiotics on the immune response to seasonal influenza vaccination in
healthy adults measured as seroprotection and seroconversion rate and increases in geometric mean
titers (GMT).

E.2.2

Secondary objectives of the trial

To investigate the effect of probiotics on selected parameters of the adaptive immune system in
healthy adults after vaccination with seasonal influenza vaccine.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Men or women in a general good state of health
2. Age 18-60 years both inclusive
3. BMI 19-30 kg/m2
4. Provided voluntary written informed consent
Subjects are eligible for randomization if they fulfill the following two criteria during the run-in period:
5. Has not taken any antibiotics during the run-in period.
6. Has been able to abstain from fermented dairy products (such as yoghurts) as well as foods and food
supplements containing probiotics during the run-in period. Single violations will be allowed.

E.4

Principal exclusion criteria

Chronic immunological diseases such as known HIV infection, rheumatoid arthritis, multiple sclerosis,
diabetes requiring insulin treatment, asthma, allergy, eczema, inflammatory bowel disease, crohn’s
disease, thyroid diseases. Subjects with chronic diseases and conditions with no potential impact on
the primary endpoint are not excluded provided they have been adequately controlled with
concomitant medication for at least three months. Subjects with hay fever may also be enrolled
outside the pollen season
2. No cancers within the past five years with the exception of carcinoma in situ and basal-cell
carcinoma.
3. Influenza vaccination current season or has already suffered from influenza during the current
season
4. Acute disease requiring treatment
5. Use of immunosuppressant medication except locally acting glucocorticoids within one month prior
to the screening visit
6. Lactose intolerance or milk protein allergy
7. Hypersensitivity to any of the components of the vaccine
8. Recent (6 months) complicated gastrointestinal (GI) surgery that may have an impact on GI tract
function
9. Oral antibiotics within one month prior to the screening visit, or within four months prior to the
screening visit if given for a recurrent condition
10. Elite athletes with intensive physical activity more than two hours/day (i.e. 14 hour/week)
11. Participation in another clinical trial within the past month
12. For women: pregnant or lactating, or wish to be pregnant during the study
13. For women: not willing to use reliable contraceptive methods. In Germany the following methods
are allowed: hormonal contraceptives (oral or implants), tubal ligation, intrauterine device, condoms
or sexual abstinence. In Denmark the following methods are allowed: hormonal contraceptives (oral
or implants), tubal ligation, intrauterine device or double barrier. Women must use reliable methods
from screening until after the final study visit..
14. Known allergy or systemic allergy-like hypersensitivity to chicken protein, irrespective of the severity of the previous symptoms or of the contact route to the allergen.

E.5 End points

E.5.1

Primary end point(s)

Seroprotection rates for the three virus strains in the vaccine . Seroprotection rate is defined as proportion of subjects with an HAI titer ≥ 40.

E.5.1.1

Timepoint(s) of evaluation of this end point

measured at Day 21

E.5.2

Secondary end point(s)

- Seroconversion rate for each of the three virus strains in the vaccine. Seroconversion rate is defined as proportion of subjects with a pre-vaccination titer < 10 and a post-vaccination titer ≥ 40 or subjects with a pre-vaccination titer > 10 and at least a four fold increase in post-vaccination titer.
- Geometric mean titers (GMT)
- Influenza specific secretory IgA in saliva

E.5.2.1

Timepoint(s) of evaluation of this end point

measured at Day 21

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

E.8.2.3

Other

E.8.2.3.1

Comparator description

diary product with and without probiotics

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

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

Last patient last visit

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:

1058

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

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

356

F.4.2

For a multinational trial

F.4.2.1

In the EEA

1058

F.4.2.2

In the whole clinical trial

1058

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)

Healthy volunteers will participate in this study; therefore, no further treatment is expected after the end of study. In the case subjects are exhibiting either subjective or objective abnormalities when the trial has been completed, they will be followed up until the condition is resolved or there is an adequate explanation.

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

2011-08-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-09-06

P. End of Trial
P.	End of Trial Status	Completed

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