Clinical Trials Register

Summary
EudraCT Number:	2019-004008-36
Sponsor's Protocol Code Number:	VRV09
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2020-09-07
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2019-004008-36

A.3

Full title of the trial

Immunogenicity and Safety of a Purified Vero Rabies Vaccine– Serum Free (VRVg) Assessed with the Institut Pasteur du Cambodge (IPC: 2-2-2-0-0) and the Thai Red Cross (TRC: 2-2-2-0-2) Intradermal Regimens as Simulated Rabies Post-exposure Prophylaxis in Healthy Subjects in Thailand

A.3.1

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

Study of Purified Vero Rabies Vaccine Compared with a Reference Rabies Vaccine as Simulated Rabies Post-Exposure Prophylaxis in Adult and Pediatric population in Thaïland

A.4.1

Sponsor's protocol code number

VRV09

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1227-4143

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/219/2018

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sanofi Pasteur SA
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	Sanofi Pasteur SA
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	Sanofi Pasteur
B.5.2	Functional name of contact point	Trial Transparency Team
B.5.3	Address:
B.5.3.1	Street Address	-
B.5.3.2	Town/ city	-
B.5.3.3	Post code	-
B.5.3.4	Country	France
B.5.4	Telephone number	----
B.5.5	Fax number	----
B.5.6	E-mail	Contact-US@sanofi.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	VRVg
D.3.2	Product code	382
D.3.4	Pharmaceutical form	Powder and solvent for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intradermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Purified Vero Rabies Vaccine - Serum Free (VRVg)
D.3.9.3	Other descriptive name	RABIES VIRUS (INACTIVATED) STRAIN WISTAR (PM/WI 38-1503-3M)
D.3.9.4	EV Substance Code	SUB25743
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	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	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	Verorab®
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pasteur
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	Verorab
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	Intradermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Purified inactivated rabies vaccine
D.3.9.3	Other descriptive name	RABIES VIRUS (INACTIVATED) STRAIN WISTAR (PM/WI 38-1503-3M)
D.3.9.4	EV Substance Code	SUB25743
D.3.10	Strength
D.3.10.1	Concentration unit	IU/ml international unit(s)/millilitre
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	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.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

Rabies (Healthy Volunteers)

E.1.1.1

Medical condition in easily understood language

Rabies

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	20.0
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To describe the immune response induced by VRVg-2 and Verorab vaccine at Day 14 (to assess the immune response after 3 doses [2-2-2]) and Day 42 (to assess the immune response after 4 doses [2-2-2-0-2]) when administered as standalone in healthy pediatric population or co-administered with HRIG (Group 5 and Group 6) at Day 0 in healthy adults

E.2.2

Secondary objectives of the trial

• To describe the immune response induced by VRVg-2 and Verorab vaccine at Day 14 (to assess the immune response after 3 doses [2-2-2]) when co-administered with ERIG (Group 3 and Group 4) at Day 0 in healthy adults
• To describe the immune response induced by VRVg-2 and Verorab vaccine at Day 90 (to assess the immune response 90 days post-rabies simulated exposure, which covers the rabies incubation period of the majority of cases) when administered as standalone in healthy pediatric population or co-administered with HRIG (Group 5 and Group 6) at Day 0 in healthy adults
• To describe the safety profile of VRVg-2 and Verorab vaccine as standalone in pediatric population or when co-administered with ERIG (Group 3 and Group 4) or HRIG (Group 5 and Group 6) at Day 0 in adults, after each vaccination

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Aged ≥ 1 year on the day of inclusion
- Participant (adult ≥ 18 years without upper age limit) or participant and participant’s parent/LAR (child ≥ 1 to < 18 years) are able to attend all scheduled visits and to comply with all study procedures
The following criterion only applies to healthy adults ≥ 18 years:
- Body Mass Index (BMI): 18.5 kg/m2 ≤ BMI ≤ 30 kg/m2

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
- Pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until 1 month after each vaccination. To be considered of non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, or surgically sterile.
- Participation at the time of study enrollment or, planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure
- Receipt of any vaccine in the 4 weeks (28 days) preceding the first study vaccination or planned receipt of any vaccine prior to Visit 8 (D90)
- Previous vaccination against rabies (in pre- or post-exposure regimen) with either the study vaccines or another vaccine
- Bite by, or exposure to a potentially rabid animal in the previous 6 months without post-exposure prophylaxis
- Receipt of immune globulins, blood or blood-derived products in the past 3 months
- Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
- At high risk for rabies exposure
- Known systemic hypersensitivity to any of the study/control vaccine components or, for adults, to equine rabies immunoglobulin ERIG (Group 3 and Group 4) or HRIG (Group 5 and Group 6), or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances
- Positive skin test to ERIG at Visit 1 for only adult participants enrolled in Group 3 and Group 4 as per superseded Protocol version 5.0
- Self-reported thrombocytopenia
- Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion
- Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily
- Current alcohol or substance abuse that, in the opinion of the Investigator, might interfere with the study conduct or completion
- Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with study conduct or completion
- Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature ≥ 38.0°C). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided
- Personal history of Guillain-Barré syndrome
- Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study, or identified as an immediate family member (ie, parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study
- Receipt of chloroquine or hydroxychloroquine up to 2 months prior to the study or through to study until Visit 8
involvement in the proposed study
- Receipt of chloroquine or hydroxychloroquine up to 2 months prior to the study or through to study until Visit 8

E.5 End points

E.5.1

Primary end point(s)

1 - Percentage of participants in Group 1, Group 2, Group 5 and Group 6 achieving rabies virus neutralizing antibody (RVNA) titer greater than or equal to (≥) 0.5 IU/mL ; RVNA titers will be measured by rapid fluorescent focus inhibition test (RFFIT)
2 - Percentage of participants in Group 1, Group 2, Group 5 and Group 6 achieving RVNA titer greater than or equal to (≥) 0.5 IU/mL ; RVNA titers will be measured by RFFIT
3 - Number of Participants in Group 1, Group 2, Group 5 and Group 6 achieving RVNA titer greater than or equal to (≥) lower limit of quantification ;
RVNA titers will be measured by RFFIT
Lower limit of quantification for RFFIT assay is 0.2 IU/mL
4 - Number of Participants in Group 1, Group 2, Group 5 and Group 6 achieving RVNA titer greater than or equal to (≥) lower limit of quantification ;
RVNA titers will be measured by RFFIT
Lower limit of quantification for RFFIT assay is 0.2 IU/mL
5 - Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 1, Group 2, Group 5 and Group 6 Participants ;
RVNA titers against rabies virus will be measured by RFFIT at Day 0 and Day 14
RVNA ratios Day14/Day0 will be calculated
6 - Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 1, Group 2, Group 5 and Group 6 Participants ;
RVNA titers against rabies virus will be measured by RFFIT at Day 0 and Day 42
RVNA ratios Day14/Day0 will be calculated

E.5.1.1

Timepoint(s) of evaluation of this end point

1, 3, 5 - Day 14 (post-vaccination)
2, 4, 6 - Day 42 (post-vaccination)

E.5.2

Secondary end point(s)

1 - Number of participants reporting immediate adverse events (AEs) ; Includes unsolicited (spontaneously reported) systemic AEs
2 - Percentage of participants reporting solicited injection site reactions ; Solicited injection site reactions:
- tenderness, erythema, swelling in toddlers (aged ≥ 1 year to < 2 years)
- pain, erythema, and swelling in children (aged 2 years to < 12 years), in adolescents and adults (aged ≥ 12 years)
3 - Percentage of participants reporting solicited systemic reactions ; Solicited systemic reactions:
- fever, vomiting, crying abnormal, drowsiness, appetite lost, irritability in toddlers (aged ≥ 1 year to < 2 years)
- fever, headache, malaise and myalgia in children (aged 2 years to < 12 years), adolescents or adults (aged ≥ 12 years)
4 - Number of participants reporting unsolicited injection site AEs ; Unsolicited (spontaneously reported) injection site AEs
5 - Number of participants reporting unsolicited systemic AEs ; Unsolicited (spontaneously reported) systemic AEs
6 - Number of participants reporting serious adverse events (SAEs) ; SAEs, including adverse event of special interest (AESIs)
7 - Percentage of participants in Group 3 and Group 4 achieving rabies virus neutralizing antibody (RVNA) titer greater than or equal to (≥) 0.5 IU/mL ; RVNA titers will be measured by RFFIT
8 - Number of Participants in Group 3 and Group 4 achieving RVNA titer greater than or equal to (≥) lower limit of quantification ; RVNA titers will be measured by RFFIT
Lower limit of quantification for RFFIT assay is 0.2 IU/mL
9 - Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 3 and Group 4 Participants ; RVNA titers against rabies virus will be measured by RFFIT at Day 0 and Day 14
RVNA ratios Day14/Day0 will be calculated
10 - Percentage of participants in Group 1, Group 2, Group 5 and Group 6 achieving rabies virus neutralizing antibody (RVNA) titer greater than or equal to (≥) 0.5 IU/mL ; RVNA titers will be measured by RFFIT
11 - Number of Participants in Group 1, Group 2, Group 5 and Group 6 achieving RVNA titer greater than or equal to (≥) lower limit of quantification ; RVNA titers will be measured by RFFIT
Lower limit of quantification for RFFIT assay is 0.2 IU/mL
12 - Geometric Mean Titer Ratio (GMTR) of individual RVNA titer: (post-/pre-vaccination) in Group 1, Group 2, Group 5 and Group 6 Participants ; RVNA titers against rabies virus will be measured by RFFIT at Day 0 and Day 90
RVNA ratios Day90/Day0 will be calculated

E.5.2.1

Timepoint(s) of evaluation of this end point

1 - Within 30 minutes post-vaccination
2 - Within 7 days post-vaccination
3 - Between Day 0 and Day 3, between Day 3 and Day 7, and during the 7 days following the remaining vaccinations
4 - Within 28 days post-vaccination
5 - Between each vaccination and up to 28 days after the last vaccination
6 - Up to 6 months post-vaccination
7, 8, 9 - Day 14 (post-vaccination)
10, 11, 12 - Day 90 (post-vaccination)

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

E.6.4

Safety

Yes

E.6.5

Efficacy

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Thailand

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

Month 7 safety follow-up telephone call (approximately 6 months after last vaccination).

E.8.9 Initial estimate of the duration of the trial

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

Yes

F.1.1

Number of subjects for this age range:

168

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

200

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

376

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

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	Thailand

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