Clinical Trials Register

Summary
EudraCT Number:	2011-005173-23
Sponsor's Protocol Code Number:	V49_23
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-02-06
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

Austria - BASG

A.2

EudraCT number

2011-005173-23

A.3

Full title of the trial

A Phase III, Multicenter, Observer-blind, Safety and Immunogenicity Study of Rabies Vaccine and Japanese Encephalitis Vaccine Administered Concomitantly and/or Separately According to 1 of 2 Different Pre-exposure Prophylaxis Schedules to Healthy Adult Subjects

A.3.1

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

Immunogenicity Study of Rabies Vaccine and Japanese Encephalitis Vaccine Administered Together and/or Separately According to Different Schedules to Healthy Subjects

A.4.1

Sponsor's protocol code number

V49_23

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	Novartis Vaccines and Diagnostics GmbH
B.1.3.4	Country	Germany
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	Novartis Vaccines and Diagnostics GmbH
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma BV
B.5.2	Functional name of contact point	Senior Specialist Regulatory Aff.
B.5.3	Address:
B.5.3.1	Street Address	Hullenbergweg 83-85
B.5.3.2	Town/ city	Amsterdam
B.5.3.3	Post code	1101 CL
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	31205640501
B.5.5	Fax number	31205640565
B.5.6	E-mail	pieter.luchtenburg@novartis.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	Rabipur
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Vaccines and Diagnostics GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Rabipur
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Rabies virus (inactivated, strain Flury LEP)
D.3.9.3	Other descriptive name	RABIES VIRUS (INACTIVATED) STRAIN FLURY LEP
D.3.9.4	EV Substance Code	SUB25746
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	2.5
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	Yes
D.2.1.1.1	Trade name	IXIARO
D.2.1.1.2	Name of the Marketing Authorisation holder	Intercell AG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	IXIARO
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Japanese Encephalitis Vaccine (inactivated, adsorbed)
D.3.9.3	Other descriptive name	JAPANESE ENCEPHALITIS VACCINE (INACTIVATED, ADSORBED)
D.3.9.4	EV Substance Code	SUB30399
D.3.10	Strength
D.3.10.1	Concentration unit	ng nanogram(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	460
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.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	Solution for injection
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Safety and Immunogenicity of Rabies Vaccine and Japanese Encephalitis Vaccine administered concomitantly and/or separately according to 1 of 2 different pre-exposure prophylaxis schedules to healthy adult subjects.

E.1.1.1

Medical condition in easily understood language

Safety and Immunogenicity of Rabies Vaccine and Japanese Encephalitis Vaccine

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	PT
E.1.2	Classification code	10037742
E.1.2	Term	Rabies
E.1.2	System Organ Class	10021881 - Infections and infestations

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	10023123
E.1.2	Term	Japanese encephalitis
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	HLT
E.1.2	Classification code	10037743
E.1.2	Term	Rabies viral infections
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 evaluate the safety and tolerability of Rabies and JE vaccines given concomitantly or alone and according to either of 2 schedules for pre-exposure prophylaxis

Immunogenicity:
Primary:
1. To establish non-inferiority of the immune response of Rabies vaccine (administered concomitantly with JE vaccine) accelerated schedule as compared to conventional schedule.
2. To establish non-inferiority of the immune response of JE vaccine (administered concomitantly with Rabies vaccine), accelerated schedule as compared to conventional schedule.

E.2.2

Secondary objectives of the trial

1. Establish non-inferiority of the Rabies vaccine immune response (with JE vaccine) versus Rabies vaccine alone in a Conventional vaccination schedule. 2. Establish non-inferiority of the immune response of JE vaccine (with Rabies vaccine) versus JE vaccine alone in a Conventional vaccination schedule. 3. Establish non-inferiority of the immune response of Rabies vaccine (with JE vaccine) given in an Accelerated schedule versus Rabies vaccine alone in a Conventional vaccination schedule. 4. Establish non-inferiority of the immune response of JE vaccine (with Rabies vaccine) in an Accelerated schedule versus JE vaccine alone in a Conventional vaccination schedule. 5. Evaluate antibody response kinetics in groups receiving Rabies vaccine measured by rapid fluorescent focus inhibition test (RFFIT) on Days 8, 15, 36, 91, 181 and 366. 6. Evaluate antibody response kinetics in groups receiving JE vaccine.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males and females between 18 and 65 years of age (inclusive)
2. Subjects who have given written consent after the nature of the study has been explained according to local regulatory requirements.
3. Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator.

E.4

Principal exclusion criteria

1. History of previous rabies/rabies immune globulin and/or JE immunization.
2. Any individuals with a contraindication or precaution against vaccination with Rabipur® or IXIARO® as highlighted in the package inserts of these products
3. Subjects currently receiving or planning to receive anti-malarial medications (e.g. Mefloquine) 14 days prior to Day 1 vaccination through Day 43.

E.5 End points

E.5.1

Primary end point(s)

• Percentage of subjects with RVNA titer ≥ 0.5 IU/mL
• Percentage of subjects with PRNT50 titer ≥ 1:10

Safety Endpoints:

1. Proportion of subjects with solicited local reactions for 7 days following each vaccination
2. Proportion of subjects with solicited systemic and other reactions from Day 1 (post-vaccination) through Day 14 (inclusive) and Day 29 through Day 35 (inclusive).
3. All AEs (including SAEs and AEs leading to subject withdrawal) from Day 1 (post-vaccination) through Day 57 (upon completion of clinic visit).
4. All vaccine related SAEs from Day 57 (post completion of clinic visit) through Day 366 (or study termination).
5. All concomitant medications collected from Day 1 through Day 57.

E.5.1.1

Timepoint(s) of evaluation of this end point

For RVNA titer: 7 days after the last active vaccine administration.
For PRNT50 titer: 28 days after the last active vaccine administration.

E.5.2

Secondary end point(s)

• RVNA GMT
• PRNT50 GMT

E.5.2.1

Timepoint(s) of evaluation of this end point

RVNA GMT and PRNT50 GMT: 28 days after the last active vaccine administration.

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

Yes

E.6.7

Pharmacodynamic

Yes

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

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

observer-blind

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Switzerland

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: October 2013

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

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:

660

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

560

F.4.2.2

In the whole clinical trial

660

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)

In accordance with the protocol. There are no plans for treatment or care after the subject has ended the participation in the trial, different from the expected normal treatment of the conditions.

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

2012-03-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-02-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2013-10-28

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