Download PDF

Clinical Trial Results:
Immunogenicity and Safety of a Purified Vero Rabies Vaccine - Serum Free in Comparison With Verorab® and Imovax® Rabies, in a Pre-exposure Regimen in Both Pediatric and Adult Populations and a Single Booster Dose of Purified Vero Rabies Vaccine - Serum Free Administered at 1 Year Post-3-dose Primary Series, and Between 2 up to 3 Years Post-One Week 2-Dose Primary Series in a Subset of Adults in Thailand

Summary
EudraCT number	2019-000973-22
Trial protocol	Outside EU/EEA
Global end of trial date

Results information
Results version number	v1(current)
This version publication date	02 Aug 2024
First version publication date	02 Aug 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

VRV12

ISRCTN number

US NCT number

NCT04127786

WHO universal trial number (UTN)

U1111-1217-3241

Other trial identifiers

EudraCT: 2019-000973-22

Sponsor organisation name

Sanofi Pasteur

Sponsor organisation address

14 Espace Henry Vallée, Lyon, France, 69007

Public contact

Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com

Scientific contact

Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-002234-PIP01-17

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Interim

Date of interim/final analysis

23 Aug 2023

Is this the analysis of the primary completion data?

Yes

Primary completion date

25 Mar 2020

Global end of trial reached?

Main objective of the trial

To demonstrate that VRVg-2 is non-inferior to Verorab and Imovax Rabies vaccines in each age group (pediatric and adult populations) when administered as a 3-dose PrEP regimen, in terms of proportion of subjects achieving an RVNA titer ≥ 0.5 IU/mL at D42, ie, 14 days after the 3rd injection (for Primary Series Cohort 1).

Protection of trial subjects

Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject is participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Oct 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Thailand: 1708

Worldwide total number of subjects

1708

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

336

Adolescents (12-17 years)

148

Adults (18-64 years)

1182

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

1708 participants were enrolled in the study from 21-Oct-2019 to 23-Jan-2023. Study had 2 phases: Primary series (Cohort (C)-1: 3-dose pre-exposure prophylaxis [PrEP] regimen & C-2: 1-week 2-dose PrEP regimen); & Booster Phase (C-1: booster dose 1 year after 1st primary series vaccine injection & C-2: Immunogenicity Persistence & Booster Phase C-2)

Screening details

The data cut-off date for result analysis reported below is 23-Aug-2023. The analysis contains all data in the primary series & booster phase of C-1 & data up to 28 days after the 2nd vaccination in the primary series of C-2. The booster phase of C-2 has not started yet & results for that phase will be posted at the time of final results posting.

Period 1 title

Primary Series

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Data analyst, Assessor

Blinding implementation details

The study was conducted in an observer-blind manner for cohort 1 primary series and cohort 2 primary series. Unblinded staff members, independent of the safety evaluation and other study evaluations, prepared and administered the vaccine. The Investigator or delegate in charge of safety assessment as well as the participants were blinded and did not know which vaccine was administered. Laboratory analysts for the blood sample testing remain blinded during the whole study.

Are arms mutually exclusive

Yes

Cohort-1 Group 1: VRVg-2

Arm description

Pediatric and adult participants received a total of 3 intramuscular (IM) injections of Purified Vero Rabies Vaccine – Serum Free (VRVg-2) in the primary series (1 injection each on Day 0, Day 7, and Day 28).

Arm type

Experimental

Investigational medicinal product name

VRVg

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

The investigational product is VRVg and VRVg-2 was the formulation used. A dose of 0.5 mL VRVg-2 was administered as intramuscular (IM) injection into the deltoid muscle (or anterolateral thigh for toddlers).

Cohort-1 Group 2: Verorab®

Arm description

Pediatric and adult participants received a total of 3 IM injections of Verorab® vaccine in the primary series (1 injection each on Day 0, Day 7, and Day 28).

Arm type

Active comparator

Investigational medicinal product name

Verorab®

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

A dose of 0.5 mL Verorab® was administered as IM injection into the deltoid muscle (or anterolateral thigh for toddlers).

Cohort-1 Group 3: Imovax Rabies®

Arm description

Pediatric and adult participants received a total of 3 IM injections of Imovax Rabies® vaccine in the primary series (1 injection each on Day 0, Day 7, and Day 28).

Arm type

Active comparator

Investigational medicinal product name

Imovax® Rabies

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

A dose of 1 mL Imovax® Rabies was administered as IM injection into the deltoid muscle (or anterolateral thigh for toddlers).

Cohort-2 Group 4: VRVg-2

Arm description

Adult participants received a total of 2 IM injections of VRVg-2 vaccine in the primary series (1 injection each on Day 0 and Day 7).

Arm type

Experimental

Investigational medicinal product name

VRVg

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

The investigational product is VRVg and VRVg-2 was the formulation used. A dose of 0.5 mL VRVg-2 was administered as IM injection into the deltoid muscle (or anterolateral thigh for toddlers).

Cohort-2 Group 5: Verorab®

Arm description

Adult participants received a total of 2 IM injections of Verorab® vaccine in the primary series (1 injection each on Day 0 and Day 7).

Arm type

Active comparator

Investigational medicinal product name

Verorab®

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

A dose of 0.5 mL Verorab® was administered as IM injection into the deltoid muscle (or anterolateral thigh for toddlers).

Cohort-2 Group 6: Imovax Rabies®

Arm description

Adult participants received a total of 2 IM injections of Imovax Rabies® vaccine in the primary series (1 injection each on Day 0 and Day 7).

Arm type

Active comparator

Investigational medicinal product name

Imovax® Rabies

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

A dose of 1 mL Imovax® Rabies was administered as IM injection into the deltoid muscle (or anterolateral thigh for toddlers).

Number of subjects in period 1	Cohort-1 Group 1: VRVg-2	Cohort-1 Group 2: Verorab®	Cohort-1 Group 3: Imovax Rabies®	Cohort-2 Group 4: VRVg-2	Cohort-2 Group 5: Verorab®	Cohort-2 Group 6: Imovax Rabies®
Started	607	203	200	420	139	139
Safety analysis set (SafAS)	607	202	200	419	139	139
PPAS for Day 28	519 ^[1]	169 ^[2]	160 ^[3]	342 ^[4]	120 ^[5]	124 ^[6]
Completed	599	199	196	415	137	138
Not completed	8	4	4	5	2	1
Consent withdrawn by subject	-	-	-	1	-	-
Adverse event, non-fatal	1	-	-	1	-	1
Withdrawal by Parent/Guardian	2	1	-	-	-	-
Protocol deviation	5	3	4	3	2	-

Notes
[1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This PPAS for Day 28 included all the participants in primary series Cohort 1 Group 1 who completed the 2-dose vaccination schedule with VRVg-2 (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).
[2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This PPAS for Day 28 included all the participants in primary series Cohort 1 Group 2 who completed the 2-dose vaccination schedule with Verorab® (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).
[3] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This PPAS for Day 28 included all the participants in primary series Cohort 1 Group 3 who completed the 2-dose vaccination schedule with Imovax Rabies® (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).
[4] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This PPAS for Day 28 included all the participants in primary series Cohort 2 Group 4 who completed the 2-dose vaccination schedule with VRVg-2 (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).
[5] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This PPAS for Day 28 included all the participants in primary series Cohort 2 Group 5 who completed the 2-dose vaccination schedule with Verorab® (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).
[6] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
Justification: This PPAS for Day 28 included all the participants in primary series Cohort 2 Group 6 who completed the 2-dose vaccination schedule with Imovax Rabies® (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).

Period 2 title

Booster Phase

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Carer, Data analyst, Assessor

Blinding implementation details

The cohort 1 booster phase was conducted in an observer-blind manner. Unblinded staff members, independent of the safety evaluation and other study evaluations, prepared and administered the vaccine. The Investigator or delegate in charge of safety assessment as well as the participants were blinded. The cohort 2 immunogenicity persistence and booster phase will be conducted in an open-label manner. Laboratory analysts for the blood sample testing remain blinded during the whole study.

Are arms mutually exclusive

Yes

Cohort-1 Group 1: VRVg-2 (PrEP)/VRVg-2 (Booster)

Arm description

A subset of adult participants who received 3 injections of VRVg-2 vaccine in the primary series and completed the follow-up period received a booster injection of VRVg-2 vaccine in the booster phase at Month 12.

Arm type

Experimental

Investigational medicinal product name

VRVg

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

The investigational product is VRVg and VRVg-2 was the formulation used. A dose of 0.5 mL VRVg-2 was administered as intramuscular (IM) injection into the deltoid muscle.

Cohort-1 Group 2: Verorab® (PrEP)/VRVg-2 (Booster)

Arm description

A subset of adult participants who received 3 injections of Verorab® vaccine in the primary series and completed the follow-up period received a booster injection of VRVg-2 vaccine in the booster phase at Month 12.

Arm type

Active comparator

Investigational medicinal product name

VRVg

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

The investigational product is VRVg and VRVg-2 was the formulation used. A dose of 0.5 mL VRVg-2 was administered as IM injection into the deltoid muscle.

Cohort-1 Group 3: Imovax Rabies® (PrEP)/VRVg-2 (Booster)

Arm description

A subset of adult participants who received 3 injections of Imovax Rabies® vaccine in the primary series and completed the follow-up period received a booster injection of VRVg-2 vaccine in the booster phase at Month 12.

Arm type

Active comparator

Investigational medicinal product name

VRVg

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

The investigational product is VRVg and VRVg-2 was the formulation used. A dose of 0.5 mL VRVg-2 was administered as IM injection into the deltoid muscle.

Number of subjects in period 2 ^[7]	Cohort-1 Group 1: VRVg-2 (PrEP)/VRVg-2 (Booster)	Cohort-1 Group 2: Verorab® (PrEP)/VRVg-2 (Booster)	Cohort-1 Group 3: Imovax Rabies® (PrEP)/VRVg-2 (Booster)
Started	94	31	32
SafAS	94	31	32
Completed	92	31	32
Not completed	2	0	0
Consent withdrawn by subject	2	-	-

Notes
[7] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: A subset of adult participants who received the respective vaccine in the primary series and completed the follow-up period, entered the booster phase and received booster dose of VRVg-2 vaccine at Month 12.

Baseline characteristics

Top of page

Reporting group title

Cohort-1 Group 1: VRVg-2

Reporting group description

Reporting group title

Cohort-1 Group 2: Verorab®

Reporting group description

Pediatric and adult participants received a total of 3 IM injections of Verorab® vaccine in the primary series (1 injection each on Day 0, Day 7, and Day 28).

Reporting group title

Cohort-1 Group 3: Imovax Rabies®

Reporting group description

Pediatric and adult participants received a total of 3 IM injections of Imovax Rabies® vaccine in the primary series (1 injection each on Day 0, Day 7, and Day 28).

Reporting group title

Cohort-2 Group 4: VRVg-2

Reporting group description

Adult participants received a total of 2 IM injections of VRVg-2 vaccine in the primary series (1 injection each on Day 0 and Day 7).

Reporting group title

Cohort-2 Group 5: Verorab®

Reporting group description

Adult participants received a total of 2 IM injections of Verorab® vaccine in the primary series (1 injection each on Day 0 and Day 7).

Reporting group title

Cohort-2 Group 6: Imovax Rabies®

Reporting group description

Adult participants received a total of 2 IM injections of Imovax Rabies® vaccine in the primary series (1 injection each on Day 0 and Day 7).

Reporting group values	Cohort-1 Group 1: VRVg-2	Cohort-1 Group 2: Verorab®	Cohort-1 Group 3: Imovax Rabies®	Cohort-2 Group 4: VRVg-2	Cohort-2 Group 5: Verorab®	Cohort-2 Group 6: Imovax Rabies®	Total
Number of subjects	607	203	200	420	139	139	1708
Age categorical
Units: Subjects
Infants and toddlers (28 days-23 months)	17	2	2	0	0	0	21
Children (2-11 years)	198	70	68	0	0	0	336
Adolescents (12-17 years)	90	28	30	0	0	0	148
Adults (18-64 years)	292	101	98	416	136	139	1182
From 65-84 years	10	2	2	4	3	0	21
Age Continuous
Units: years
arithmetic mean (standard deviation)	22.9 ( 17.1 )	22.6 ( 16.1 )	22.4 ( 16.1 )	37.4 ( 11.3 )	38.4 ( 11.1 )	37.3 ( 10.9 )	-
Sex: Female, Male
Units: participants
Female	399	147	122	266	96	98	1128
Male	208	56	78	154	43	41	580
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0
Asian	607	203	200	420	139	139	1708
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0
Black or African American	0	0	0	0	0	0	0
White	0	0	0	0	0	0	0
More than one race	0	0	0	0	0	0	0
Unknown or Not Reported	0	0	0	0	0	0	0

Subject analysis set title

Primary Series: Cohort-1 Group 1: VRVg-2

Subject analysis set type

Safety analysis

Subject analysis set description

Pediatric and adult participants who received at least one dose of VRVg-2 vaccine in the primary series Cohort 1 Group 1 (on Day 0, Day 7 or Day 28).

Subject analysis set title

Primary Series: Cohort-1 Group 2: Verorab®

Subject analysis set type

Safety analysis

Subject analysis set description

Pediatric and adult participants who received at least one dose of Verorab® vaccine in the primary series Cohort 1 Group 2 (on Day 0, Day 7 or Day 28).

Subject analysis set title

Primary Series: Cohort-1 Group 3: Imovax Rabies®

Subject analysis set type

Safety analysis

Subject analysis set description

Pediatric and adult participants who received at least one dose of Imovax Rabies® vaccine in the primary series Cohort 1 Group 3 (on Day 0, Day 7 or Day 28).

Subject analysis set title

Primary Series: Cohort-2 Group 4: VRVg-2

Subject analysis set type

Safety analysis

Subject analysis set description

Adult participants who received at least one dose of VRVg-2 vaccine in the primary series Cohort 2 Group 4 (on Day 0 or Day 7).

Subject analysis set title

Primary Series: Cohort-2 Group 5: Verorab®

Subject analysis set type

Safety analysis

Subject analysis set description

Adult participants who received at least one dose of Verorab® vaccine in the primary series Cohort 2 Group 5 (on Day 0 or Day 7).

Subject analysis set title

Primary Series: Cohort-2 Group 6: Imovax Rabies®

Subject analysis set type

Safety analysis

Subject analysis set description

Adult participants who received at least one dose of Imovax Rabies® vaccine in the primary series Cohort 2 Group 6 (on Day 0 or Day 7).

Subject analysis set title

Primary Series: Cohort-1 Group 1: VRVg-2

Subject analysis set type

Per protocol

Subject analysis set description

This per-protocol analysis set (PPAS) for Day 42 included all the participants in primary series Cohort 1 Group 1 who completed the 3-dose vaccination schedule with VRVg-2 (on Day 0, Day 7 and Day 28), with no relevant protocol deviation before Day 42 (i.e., 14 days after the third vaccine).

Subject analysis set title

Primary Series: Cohort-1 Group 2: Verorab®

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for Day 42 included all the participants in primary series Cohort 1 Group 2 who completed the 3-dose vaccination schedule with Verorab® (on Day 0, Day 7 and Day 28), with no relevant protocol deviation before Day 42 (i.e., 14 days after the third vaccine).

Subject analysis set title

Primary Series: Cohort-1 Group 3: Imovax Rabies®

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for Day 42 included all the participants in primary series Cohort 1 Group 3 who completed the 3-dose vaccination schedule with Imovax Rabies® (on Day 0, Day 7 and Day 28), with no relevant protocol deviation before Day 42 (i.e., 14 days after the third vaccine).

Subject analysis set title

Pooled Groups 1 and 4: VRVg-2

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for Day 28 included all the participants in primary series, Cohort 1 Group 1 and Cohort 2 Group 4 who completed the 2-dose vaccination schedule with VRVg-2 (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).

Subject analysis set title

Pooled Groups 2 and 5: Verorab®

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for Day 28 included all the participants in primary series, Cohort 1 Group 2 and Cohort 2 Group 5 who completed the 2-dose vaccination schedule with Verorab® (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).

Subject analysis set title

Pooled Groups 3 and 6: Imovax Rabies®

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for Day 28 included all the participants in primary series, Cohort 1 Group 3 and Cohort 2 Group 6 who completed the 2-dose vaccination schedule with Imovax Rabies® (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).

Subject analysis set title

Primary Series: Cohort-2 Group 4: VRVg-2

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for Day 28 included all the participants in primary series Cohort 2 Group 4 who completed the 2-dose vaccination schedule with VRVg-2 (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).

Subject analysis set title

Primary Series: Cohort-2 Group 5: Verorab®

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for Day 28 included all the participants in primary series Cohort 2 Group 5 who completed the 2-dose vaccination schedule with Verorab® (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).

Subject analysis set title

Primary Series: Cohort-2 Group 6: Imovax Rabies®

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for Day 28 included all the participants in primary series Cohort 2 Group 6 who completed the 2-dose vaccination schedule with Imovax Rabies® (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).

Subject analysis set title

Booster Phase: Cohort-1 Group 1: VRVg-2 (Primed With VRVg-2)

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for booster at Month 12 included a subset of adult participants who completed the 3-dose vaccination schedule with VRVg-2 in the primary series Cohort 1 Group 1 and received a booster injection of VRVg-2 vaccine in the booster phase at Month 12, with no relevant protocol deviation before Month 12 + Day 14 (i.e., 14 days after the booster dose injection).

Subject analysis set title

Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® Primed)

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for booster at M12 included a subset of adult participants who completed the 3-dose vaccination schedule with Verorab® in the primary series Cohort 1 Group 2 and received a booster injection of VRVg-2 vaccine in the booster phase at Month 12, with no relevant protocol deviation before Month 12 + Day 14 (i.e., 14 days after the booster dose injection).

Subject analysis set title

Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for booster at M12 included a subset of adult participants who completed the 3-dose vaccination schedule with Imovax Rabies® in the primary series Cohort 1 Group 3 and received a booster injection of VRVg-2 vaccine in the booster phase at Month 12, with no relevant protocol deviation before Month 12 + Day 14 (i.e., 14 days after the booster dose injection).

Subject analysis set title

Primary Series: Cohort-1 Group 1: VRVg-2

Subject analysis set type

Safety analysis

Subject analysis set description

Pediatric and adult participants who received at least one dose of VRVg-2 vaccine in the primary series Cohort 1 Group 1 (on Day 0, Day 7 or Day 28).

Subject analysis set title

Primary Series: Cohort-1 Group 2: Verorab®

Subject analysis set type

Safety analysis

Subject analysis set description

Pediatric and adult participants who received at least one dose of Verorab® vaccine in the primary series Cohort 1 Group 2 (on Day 0, Day 7 or Day 28).

Subject analysis set title

Primary Series: Cohort-2 Group 4: VRVg-2

Subject analysis set type

Safety analysis

Subject analysis set description

Adult participants who received at least one dose of VRVg-2 vaccine in the primary series Cohort 2 Group 4 (on Day 0 or Day 7).

Subject analysis set title

Booster Phase: Cohort-1 Group 1: VRVg-2 (primed with VRVg-2)

Subject analysis set type

Safety analysis

Subject analysis set description

This Safety Analysis Set for booster (SafASB) included a subset of adult participants who completed the 3-dose vaccination schedule with VRVg-2 in the primary series Cohort 1 Group 1 and received a booster injection of VRVg-2 vaccine in the booster phase at Month 12.

Subject analysis set title

Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® primed)

Subject analysis set type

Safety analysis

Subject analysis set description

This SafASB included a subset of adult participants who completed the 3-dose vaccination schedule with Verorab® in the primary series Cohort 1 Group 2 and received a booster injection of VRVg-2 vaccine in the booster phase at Month 12.

Subject analysis set title

Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)

Subject analysis set type

Safety analysis

Subject analysis set description

This SafASB included a subset of adult participants who completed the 3-dose vaccination schedule with Imovax Rabies® in the primary series Cohort 1 Group 3 and received a booster injection of VRVg-2 vaccine in the booster phase at Month 12.

Subject analysis set title

Primary Series: Cohort-1 Group 3: Imovax Rabies®

Subject analysis set type

Per protocol

Subject analysis set description

This PPAS for Day 28 included all the participants in primary series Cohort 1 Group 3 who completed the 2-dose vaccination schedule with Imovax Rabies® (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine).

Subject analysis sets values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®	Pooled Groups 1 and 4: VRVg-2	Pooled Groups 2 and 5: Verorab®	Pooled Groups 3 and 6: Imovax Rabies®	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®	Booster Phase: Cohort-1 Group 1: VRVg-2 (Primed With VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® Primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-2 Group 4: VRVg-2	Booster Phase: Cohort-1 Group 1: VRVg-2 (primed with VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)	Primary Series: Cohort-1 Group 3: Imovax Rabies®
Number of subjects	607	203	200	420	139	139	519	169	162	861	289	284	342	120	124	80	26	28	607	202	419	94	31	32	20
Age categorical
Units: Subjects
Infants and toddlers (28 days-23 months)
Children (2-11 years)
Adolescents (12-17 years)
Adults (18-64 years)
From 65-84 years
Age Continuous
Units: years
arithmetic mean (standard deviation)	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	( )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )	0 ( )	( )
Sex: Female, Male
Units: participants
Female
Male
Race (NIH/OMB)
Units: Subjects
American Indian or Alaska Native
Asian
Native Hawaiian or Other Pacific Islander
Black or African American
White
More than one race
Unknown or Not Reported

End points

Top of page

Reporting group title

Cohort-1 Group 1: VRVg-2

Reporting group description

Reporting group title

Cohort-1 Group 2: Verorab®

Reporting group description

Pediatric and adult participants received a total of 3 IM injections of Verorab® vaccine in the primary series (1 injection each on Day 0, Day 7, and Day 28).

Reporting group title

Cohort-1 Group 3: Imovax Rabies®

Reporting group description

Pediatric and adult participants received a total of 3 IM injections of Imovax Rabies® vaccine in the primary series (1 injection each on Day 0, Day 7, and Day 28).

Reporting group title

Cohort-2 Group 4: VRVg-2

Reporting group description

Adult participants received a total of 2 IM injections of VRVg-2 vaccine in the primary series (1 injection each on Day 0 and Day 7).

Reporting group title

Cohort-2 Group 5: Verorab®

Reporting group description

Adult participants received a total of 2 IM injections of Verorab® vaccine in the primary series (1 injection each on Day 0 and Day 7).

Reporting group title

Cohort-2 Group 6: Imovax Rabies®

Reporting group description

Adult participants received a total of 2 IM injections of Imovax Rabies® vaccine in the primary series (1 injection each on Day 0 and Day 7).

Reporting group title

Cohort-1 Group 1: VRVg-2 (PrEP)/VRVg-2 (Booster)

Reporting group description

Reporting group title

Cohort-1 Group 2: Verorab® (PrEP)/VRVg-2 (Booster)

Reporting group description

Reporting group title

Cohort-1 Group 3: Imovax Rabies® (PrEP)/VRVg-2 (Booster)

Reporting group description

Subject analysis set title

Primary Series: Cohort-1 Group 1: VRVg-2

Subject analysis set type

Safety analysis

Subject analysis set description

Pediatric and adult participants who received at least one dose of VRVg-2 vaccine in the primary series Cohort 1 Group 1 (on Day 0, Day 7 or Day 28).

Subject analysis set title

Primary Series: Cohort-1 Group 2: Verorab®

Subject analysis set type

Safety analysis

Subject analysis set description

Pediatric and adult participants who received at least one dose of Verorab® vaccine in the primary series Cohort 1 Group 2 (on Day 0, Day 7 or Day 28).

Subject analysis set title

Primary Series: Cohort-1 Group 3: Imovax Rabies®

Subject analysis set type

Safety analysis

Subject analysis set description

Pediatric and adult participants who received at least one dose of Imovax Rabies® vaccine in the primary series Cohort 1 Group 3 (on Day 0, Day 7 or Day 28).

Subject analysis set title

Primary Series: Cohort-2 Group 4: VRVg-2

Subject analysis set type

Safety analysis

Subject analysis set description

Adult participants who received at least one dose of VRVg-2 vaccine in the primary series Cohort 2 Group 4 (on Day 0 or Day 7).

Subject analysis set title

Primary Series: Cohort-2 Group 5: Verorab®

Subject analysis set type

Safety analysis

Subject analysis set description

Adult participants who received at least one dose of Verorab® vaccine in the primary series Cohort 2 Group 5 (on Day 0 or Day 7).

Subject analysis set title

Primary Series: Cohort-2 Group 6: Imovax Rabies®

Subject analysis set type

Safety analysis

Subject analysis set description

Adult participants who received at least one dose of Imovax Rabies® vaccine in the primary series Cohort 2 Group 6 (on Day 0 or Day 7).

Subject analysis set title

Primary Series: Cohort-1 Group 1: VRVg-2

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Primary Series: Cohort-1 Group 2: Verorab®

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Primary Series: Cohort-1 Group 3: Imovax Rabies®

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Pooled Groups 1 and 4: VRVg-2

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Pooled Groups 2 and 5: Verorab®

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Pooled Groups 3 and 6: Imovax Rabies®

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Primary Series: Cohort-2 Group 4: VRVg-2

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Primary Series: Cohort-2 Group 5: Verorab®

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Primary Series: Cohort-2 Group 6: Imovax Rabies®

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Booster Phase: Cohort-1 Group 1: VRVg-2 (Primed With VRVg-2)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® Primed)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Primary Series: Cohort-1 Group 1: VRVg-2

Subject analysis set type

Safety analysis

Subject analysis set description

Pediatric and adult participants who received at least one dose of VRVg-2 vaccine in the primary series Cohort 1 Group 1 (on Day 0, Day 7 or Day 28).

Subject analysis set title

Primary Series: Cohort-1 Group 2: Verorab®

Subject analysis set type

Safety analysis

Subject analysis set description

Pediatric and adult participants who received at least one dose of Verorab® vaccine in the primary series Cohort 1 Group 2 (on Day 0, Day 7 or Day 28).

Subject analysis set title

Primary Series: Cohort-2 Group 4: VRVg-2

Subject analysis set type

Safety analysis

Subject analysis set description

Adult participants who received at least one dose of VRVg-2 vaccine in the primary series Cohort 2 Group 4 (on Day 0 or Day 7).

Subject analysis set title

Booster Phase: Cohort-1 Group 1: VRVg-2 (primed with VRVg-2)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® primed)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)

Subject analysis set type

Safety analysis

Subject analysis set description

Subject analysis set title

Primary Series: Cohort-1 Group 3: Imovax Rabies®

Subject analysis set type

Per protocol

Subject analysis set description

Primary: Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 IU/mL

Top of page

End point title

Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 IU/mL

End point description

RVNA titer against rabies virus was assessed using the Rapid Fluorescent Focus Inhibition test (RFFIT) assay method. Results are based on the per-protocol analysis set (PPAS) for Day 42 (3-dose) which included all the participants in primary series Cohort 1 Groups 1, 2 and 3 who completed their respective 3-dose vaccination schedule (on Day 0, Day 7 and Day 28), with no relevant protocol deviation before Day 42 (i.e., 14 days after the third vaccine). Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Primary

End point timeframe

Day 42 (post-vaccination)

End point values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®
Number of subjects analysed	519	169	162
Units: percentage of participants
number (confidence interval 95%)
Pediatric (< 18 years): n=265, 85, 83	100 (98.6 to 100)	100 (95.8 to 100)	100 (95.7 to 100)
Adult (>= 18 years): n=254, 84, 79	100 (98.6 to 100)	98.8 (93.5 to 100)	100 (95.4 to 100)

Statistical Analysis 1 for Primary Series Cohort 1

Statistical analysis description

‘Primary Series: Cohort-1 Group 1: VRVg-2(pediatric)’ versus (v) ‘Primary Series: Cohort-1 Group 2: Verorab® (pediatric)’. The following ‘Number of subjects included in analysis’ is being erroneously displayed as 688. Actual ‘number of subjects included in analysis’ is 350 (i.e., 265 pediatric participants in ‘Primary Series: Cohort-1 Group 1: VRVg-2’ and 85 pediatric participants in ‘Primary Series: Cohort-1 Group 2: Verorab®’).

Comparison groups

Primary Series: Cohort-1 Group 1: VRVg-2 v Primary Series: Cohort-1 Group 2: Verorab®

Number of subjects included in analysis

688

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[1]

Method

Parameter type

Percentage Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

4.3

Notes
[1] - Non-inferiority was demonstrated if the lower limit of the 95 percent (%) confidence interval (CI) of the difference of the percentages between the test group (Group 1) and control groups (Group 2, Group 3) was greater than (>) -5% at Day 42.

Statistical Analysis 3 for Primary Series Cohort 1

Statistical analysis description

‘Primary Series: Cohort-1 Group 1: VRVg-2 (pediatric)’ versus ‘Primary Series: Cohort-1 Group 3: Imovax Rabies® (pediatric)’. The following ‘Number of subjects included in analysis’ is being erroneously displayed as 681. Actual ‘number of subjects included in analysis’ is 348 (i.e., 265 pediatric participants in ‘Primary Series: Cohort-1 Group 1: VRVg-2’ and 83 pediatric participants in ‘Primary Series: Cohort-1 Group 3: Imovax Rabies®’).

Comparison groups

Primary Series: Cohort-1 Group 1: VRVg-2 v Primary Series: Cohort-1 Group 3: Imovax Rabies®

Number of subjects included in analysis

681

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Parameter type

Percentage Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

4.4

Notes
[2] - Non-inferiority was demonstrated if the lower limit of the 95% CI of the difference of the percentages between the test group (Group 1) and control groups (Group 2, Group 3) was > -5% at Day 42.

Statistical Analysis 4 for Primary Series Cohort 1

Statistical analysis description

‘Primary Series: Cohort-1 Group 1: VRVg-2 (adult)’ versus ‘Primary Series: Cohort-1 Group 3: Imovax Rabies® (adult)’. The following ‘Number of subjects included in analysis’ is being erroneously displayed as 681. Actual ‘number of subjects included in analysis’ is 333 (i.e., 254 adult participants in ‘Primary Series: Cohort-1 Group 1: VRVg-2’ and 79 adult participants in ‘Primary Series: Cohort-1 Group 3: Imovax Rabies®’).

Comparison groups

Primary Series: Cohort-1 Group 1: VRVg-2 v Primary Series: Cohort-1 Group 3: Imovax Rabies®

Number of subjects included in analysis

681

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

Method

Parameter type

Percentage Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

4.6

Notes
[3] - Non-inferiority was demonstrated if the lower limit of the 95% CI of the difference of the percentages between the test group (Group 1) and control groups (Group 2, Group 3) was > -5% at Day 42.

Statistical Analysis 2 for Primary Series Cohort 1

Statistical analysis description

‘Primary Series: Cohort-1 Group 1: VRVg-2 (adult)’ versus ‘Primary Series: Cohort-1 Group 2: Verorab® (adult). The following ‘number of subjects included in analysis’ is being erroneously displayed as 688. Actual ‘number of subjects included in analysis’ is 338 (i.e., 254 adult participants in ‘Primary Series: Cohort-1 Group 1: VRVg-2’ and 84 adult participants in ‘Primary Series: Cohort-1 Group 2: Verorab®’).

Comparison groups

Primary Series: Cohort-1 Group 1: VRVg-2 v Primary Series: Cohort-1 Group 2: Verorab®

Number of subjects included in analysis

688

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Parameter type

Percentage Difference

Point estimate

1.2

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

6.4

Notes
[4] - Non-inferiority was demonstrated if the lower limit of the 95% CI of the difference of the percentages between the test group (Group 1) and control groups (Group 2, Group 3) was > -5% at Day 42.

Secondary: Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

Top of page

End point title

Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. Results are based on the PPAS for Day 42 (3-dose) for primary series Cohort 1 Groups 1, 2 and 3. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Cohort 1: Day 0 (pre-vaccination), Day 28 and Day 42 (post-vaccination)

End point values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®
Number of subjects analysed	519	169	162
Units: percentage of participants
number (confidence interval 95%)
Day 0: n=519, 169, 162	0 (0 to 0.7)	0 (0 to 2.2)	0 (0 to 2.3)
Day 28: n=512, 168, 160	100 (99.3 to 100)	99.4 (96.7 to 100)	98.8 (95.6 to 99.8)
Day 42: n=519, 169, 162	100 (99.3 to 100)	99.4 (96.7 to 100)	100 (97.7 to 100)

No statistical analyses for this end point

Secondary: Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population

Top of page

End point title

Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. It was planned to collect and present pooled data of specified Groups, and separately for adults and pediatric participants in this outcome measure. Results are based on the PPAS for Day 28 (2-dose) which included all the participants in pooled ‘Groups 1 and 4’; pooled ‘Groups 2 and 5’; and pooled ‘Groups 3 and 6’ who completed their respective 2-dose vaccination schedule (on Day 0 and Day 7), with no relevant protocol deviation before Day 28 (i.e., 21 days after the second vaccine). Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Day 28

End point values	Pooled Groups 1 and 4: VRVg-2	Pooled Groups 2 and 5: Verorab®	Pooled Groups 3 and 6: Imovax Rabies®
Number of subjects analysed	861	289	284
Units: percentage of participants
number (confidence interval 95%)
Pediatric (< 18 years): n=266, 86, 81	100 (98.6 to 100)	100 (95.8 to 100)	100 (95.5 to 100)
Adult (>= 18 years): n=595, 203, 203	98.3 (96.9 to 99.2)	98.5 (95.7 to 99.7)	96.6 (93.0 to 98.6)

Statistical Analysis 1 for Primary Series

Statistical analysis description

‘Pooled Groups 1 and 4: VRVg-2 (pediatric)’ versus (v) ‘Pooled Groups 2 and 5: Verorab® (pediatric)’. The following ‘Number of subjects included in analysis’ is being erroneously displayed as 1150. Actual ‘number of subjects included in analysis’ is 352 (i.e., 266 pediatric participants in ‘Pooled Groups 1 and 4: VRVg-2’ and 86 pediatric participants in ‘Pooled Groups 2 and 5: Verorab®’).

Comparison groups

Pooled Groups 1 and 4: VRVg-2 v Pooled Groups 2 and 5: Verorab®

Number of subjects included in analysis

1150

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

Method

Parameter type

Percentage Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

4.3

Notes
[5] - Non-inferiority was demonstrated if the lower limit of the 95% CI of the difference of the percentage between the test groups (Groups 1+4) and control groups (Groups 2+5, Groups 3+6) was > -5% at Day 28.

Statistical Analysis 4 for Primary Series

Statistical analysis description

‘Pooled Groups 1 and 4: VRVg-2 (adult)’ versus ‘Pooled Groups 3 and 6: Imovax Rabies® (adult)’. The following ‘Number of subjects included in analysis’ is being erroneously displayed as 1150. Actual ‘number of subjects included in analysis’ is 798 (i.e., 595 adult participants in ‘Pooled Groups 1 and 4: VRVg-2’ and 203 adult participants in ‘Pooled Groups 3 and 6: Imovax Rabies®’).

Comparison groups

Pooled Groups 1 and 4: VRVg-2 v Pooled Groups 3 and 6: Imovax Rabies®

Number of subjects included in analysis

1145

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[6]

Method

Parameter type

Percentage Difference

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

5.3

Notes
[6] - Non-inferiority was demonstrated if the lower limit of the 95% CI of the difference of the percentage between the test groups (Groups 1+4) and control groups (Groups 2+5, Groups 3+6) was > -5% at Day 28.

Statistical Analysis 3 for Primary Series

Statistical analysis description

‘Pooled Groups 1 and 4: VRVg-2 (pediatric)’ versus ‘Pooled Groups 3 and 6: Imovax Rabies® (pediatric)’. The following ‘Number of subjects included in analysis’ is being erroneously displayed as 1150. Actual ‘number of subjects included in analysis’ is 347 (i.e., 266 pediatric participants in ‘Pooled Groups 1 and 4: VRVg-2’ and 81 pediatric participants in ‘Pooled Groups 3 and 6: Imovax Rabies®’).

Comparison groups

Pooled Groups 1 and 4: VRVg-2 v Pooled Groups 3 and 6: Imovax Rabies®

Number of subjects included in analysis

1145

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

Method

Parameter type

Percentage Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

4.5

Notes
[7] - Non-inferiority was demonstrated if the lower limit of the 95% CI of the difference of the percentage between the test groups (Groups 1+4) and control groups (Groups 2+5, Groups 3+6) was > -5% at Day 28.

Statistical Analysis 2 for Primary Series

Statistical analysis description

‘Pooled Groups 1 and 4: VRVg-2 (adult)’ versus ‘Pooled Groups 2 and 5: Verorab® (adult)’. The following ‘Number of subjects included in analysis’ is being erroneously displayed as 1150. Actual ‘number of subjects included in analysis’ is 798 (i.e., 595 adult participants in ‘Pooled Groups 1 and 4: VRVg-2’ and 203 adult participants in ‘Pooled Groups 2 and 5: Verorab®’).

Comparison groups

Pooled Groups 1 and 4: VRVg-2 v Pooled Groups 2 and 5: Verorab®

Number of subjects included in analysis

1150

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[8]

Method

Parameter type

Percentage Difference

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

2.7

Notes
[8] - Non-inferiority was demonstrated if the lower limit of the 95% CI of the difference of the percentage between the test groups (Groups 1+4) and control groups (Groups 2+5, Groups 3+6) was > -5% at Day 28.

Secondary: Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population (Groups 1 and 4) Versus Cohort 1: Group 3: Non-inferiority Analysis

Top of page

End point title

Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population (Groups 1 and 4) Versus Cohort 1: Group 3: Non-inferiority Analysis

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. It was planned to collect and present pooled data of specified groups, and separately for adults and pediatric participants in this outcome measure. Data for this outcome measure was planned to be collected at Day 28 for Pooled Groups 1 and 4 and at Day 42 for Primary Series: Cohort-1 Group 3: Imovax Rabies® and reported as overall data for the non-inferiority analysis in this outcome measure. Results are based on the PPAS for Day 28 (2-dose) for ‘pooled Groups 1 and 4’ and the PPAS for Day 42 (3-dose) for ‘primary series: Cohort 1 Group 3’. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Pooled Groups 1 and 4: Day 28 (post-vaccination) and Primary Series: Cohort-1 Group 3: Day 42 (post-vaccination)

End point values	Primary Series: Cohort-1 Group 3: Imovax Rabies®	Pooled Groups 1 and 4: VRVg-2
Number of subjects analysed	162	861
Units: percentage of participants
number (confidence interval 95%)
Pediatric (< 18 years): n=266, 83	100 (95.7 to 100)	100 (98.6 to 100)
Adult (>= 18 years): n=595, 79	100 (95.4 to 100)	98.3 (96.9 to 99.2)

Statistical Analysis 2 for Primary Series

Statistical analysis description

‘Pooled Groups 1 and 4: VRVg-2 at Day 28 (adult)’ versus ‘Primary Series: Cohort-1 Group 3: Imovax Rabies® at Day 42 (adult)’. The following ‘Number of subjects included in analysis’ is being erroneously displayed as 1023. Actual ‘number of subjects included in analysis’ is 674 (i.e., 595 adult participants in ‘Pooled Groups 1 and 4: VRVg-2 at Day 28’ and 79 adult participants in ‘Primary Series: Cohort-1 Group 3: Imovax Rabies® at Day 42’.

Comparison groups

Pooled Groups 1 and 4: VRVg-2 v Primary Series: Cohort-1 Group 3: Imovax Rabies®

Number of subjects included in analysis

1023

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

Method

Parameter type

Percentage Difference

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-3.1

upper limit

Notes
[9] - Each non-inferiority was demonstrated if the lower limit of the 95% CI of the difference of the proportions between 2-dose VRVg-2 at day (D) 28 and 3-dose Imovax Rabies® at D42 was > -10%. If the non-inferiority objective for VRVg-2 versus comparator vaccines at D28 was demonstrated, the overall non-inferiority of 2-dose VRVg-2 at D28 versus 3-dose Imovax Rabies® at D42 was demonstrated if the non-inferiority between pooled Groups 1+4 and Group 3 were both demonstrated in each age group.

Statistical Analysis 1 for Primary Series

Statistical analysis description

‘Pooled Groups 1 and 4: VRVg-2 at Day 28 (pediatric)’ versus (v) ‘Primary Series: Cohort-1 Group 3: Imovax Rabies® at Day 42 (pediatric)’. The following ‘Number of subjects included in analysis’ is being erroneously displayed as 1023. Actual ‘number of subjects included in analysis’ is 349 (i.e., 266 pediatric participants in ‘Pooled Groups 1 and 4: VRVg-2 at Day 28’ and 86 pediatric participants in ‘Primary Series: Cohort-1 Group 3: Imovax Rabies® at Day 42’.

Comparison groups

Pooled Groups 1 and 4: VRVg-2 v Primary Series: Cohort-1 Group 3: Imovax Rabies®

Number of subjects included in analysis

1023

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[10]

Method

Parameter type

Percentage Difference

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

4.4

Notes
[10] - Each non-inferiority was demonstrated if the lower limit of the 95% CI of the difference of the proportions between 2-dose VRVg-2 at day (D) 28 and 3-dose Imovax Rabies® at D42 was > -10%. If the non-inferiority objective for VRVg-2 versus comparator vaccines at D28 was demonstrated, the overall non-inferiority of 2-dose VRVg-2 at D28 versus 3-dose Imovax Rabies® at D42 was demonstrated if the non-inferiority between pooled Groups 1+4 and Group 3 were both demonstrated in each age group.

Secondary: Primary Series: Groups 1 and 4: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population - Superiority Analysis

Top of page

End point title

Primary Series: Groups 1 and 4: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population - Superiority Analysis

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. It was planned to collect and present pooled data of specified groups in this outcome measure. Results are based on the PPAS for Day 28 (2-dose) for ‘pooled Groups 1 and 4’. If the non-inferiority objective of 2-dose VRVg-2 at D28 versus 3-dose Imovax Rabies® at D42 was demonstrated based on the non-inferiority (NI) margin of -10%, the superiority of VRVg-2 at D28 was demonstrated if the overall observed proportion of subjects with an RVNA titer >= 0.5 IU/mL at D28 was at least 99% in the pooled VRVg-2 Group (Groups 1+4), with the lower limit of 95% CI was at least 97%.

End point type

Secondary

End point timeframe

Day 28 (post-vaccination)

End point values	Pooled Groups 1 and 4: VRVg-2
Number of subjects analysed	861
Units: percentage of participants
number (confidence interval 95%)	98.8 (97.9 to 99.4)

No statistical analyses for this end point

Secondary: Primary Series Cohort 1 Group 3: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Non-Inferiority Analysis

Top of page

End point title

Primary Series Cohort 1 Group 3: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Non-Inferiority Analysis

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. Results are based on the PPAS for Day 28 (2-dose) and the PPAS for Day 42 (3-dose) for ‘primary series: Cohort-1 Group 3’. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Day 28 and Day 42 (post-vaccination)

End point values	Primary Series: Cohort-1 Group 3: Imovax Rabies®
Number of subjects analysed	162
Units: percentage of participants
number (confidence interval 95%)
Day 28: n=160	98.8 (95.6 to 99.8)
Day 42: n=162	100 (97.7 to 100)

No statistical analyses for this end point

Secondary: Primary Series Cohort 1: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus

Top of page

End point title

Primary Series Cohort 1: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus

End point description

End point type

Secondary

End point timeframe

Cohort 1: Day 0 (pre-vaccination), Day 28 and Day 42 (post-vaccination)

End point values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®
Number of subjects analysed	519	169	162
Units: IU/mL
geometric mean (confidence interval 95%)
Day 0: n=519, 169, 162	0.100 (0.100 to 0.100)	0.101 (0.100 to 0.102)	0.101 (0.100 to 0.101)
Day 28: n=512, 168, 160	7.16 (6.66 to 7.69)	4.90 (4.31 to 5.57)	5.13 (4.48 to 5.87)
Day 42: n=519, 169, 162	24.0 (22.4 to 25.7)	20.0 (17.6 to 22.8)	16.4 (14.7 to 18.3)

No statistical analyses for this end point

Secondary: Primary Series Cohort 2: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus

Top of page

End point title

Primary Series Cohort 2: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. Results are based on the PPAS for Day 28 (2-dose) for primary series Cohort 2 Groups 4, 5 and 6. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination)

End point values	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®
Number of subjects analysed	342	120	124
Units: IU/mL
geometric mean (confidence interval 95%)
Day 0: n=342, 120, 124	0.101 (0.100 to 0.101)	0.101 (0.100 to 0.101)	0.100 (0.100 to 0.101)
Day 28: n=342, 120, 124	3.79 (3.42 to 4.20)	2.92 (2.45 to 3.48)	3.91 (3.25 to 4.70)

No statistical analyses for this end point

Secondary: Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

Top of page

End point title

Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

End point description

End point type

Secondary

End point timeframe

Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination)

End point values	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®
Number of subjects analysed	342	120	124
Units: percentage of participants
number (confidence interval 95%)
Day 0: n=342, 120, 124	0 (0.0 to 1.1)	0 (0.0 to 3.0)	0 (0.0 to 2.9)
Day 28: n=342, 120, 124	97.1 (94.7 to 98.6)	98.3 (94.1 to 99.8)	96.0 (90.8 to 98.7)

No statistical analyses for this end point

Secondary: Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

Top of page

End point title

Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. LLOQ for the RFFIT assay was 0.2 IU/mL. Results are based on the PPAS for Day 42 (3-dose) for primary series Cohort 1 Groups 1, 2 and 3. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Cohort 1: Day 0 (pre-vaccination), Day 28 and Day 42 (post-vaccination)

End point values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®
Number of subjects analysed	519	169	162
Units: percentage of participants
number (confidence interval 95%)
Day 0: n=519, 169, 162	0 (0 to 0.7)	0 (0 to 2.2)	0 (0 to 2.3)
Day 28: n=512, 168, 160	100 (99.3 to 100)	99.4 (96.7 to 100)	100 (97.7 to 100)
Day 42: n=519, 169, 162	100 (99.3 to 100)	99.4 (96.7 to 100)	100 (97.7 to 100)

No statistical analyses for this end point

Secondary: Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

Top of page

End point title

Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. LLOQ for the RFFIT assay was 0.2 IU/mL. Results are based on the PPAS for Day 28 (2-dose) for primary series Cohort 2 Groups 4, 5 and 6. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination)

End point values	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®
Number of subjects analysed	342	120	124
Units: percentage of participants
number (confidence interval 95%)
Day 0: n=342, 120, 124	0 (0 to 1.1)	0 (0 to 3.0)	0 (0 to 2.9)
Day 28: n=342, 120, 124	99.7 (98.4 to 100)	100 (97.0 to 100)	98.4 (94.3 to 99.8)

No statistical analyses for this end point

Secondary: Primary Series Cohort 1: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

Top of page

End point title

Primary Series Cohort 1: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. GMTRs were calculated as the ratio of GMTs post-vaccination (i.e., on Day 28 and Day 42) and pre-vaccination on Day 0. Results are based on the PPAS for Day 42 (3-dose) for primary series Cohort 1 Groups 1, 2 and 3. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Cohort 1: Day 0 (pre-vaccination), Day 28 and Day 42 (post-vaccination)

End point values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®
Number of subjects analysed	519	169	162
Units: ratio
geometric mean (confidence interval 95%)
Day 28/Day 0: n=512, 168, 160	71.5 (66.6 to 76.8)	48.7 (42.8 to 55.3)	51.0 (44.6 to 58.3)
Day 42/Day 0: n=519, 169, 162	240 (224 to 256)	199 (174 to 226)	163 (146 to 182)

No statistical analyses for this end point

Secondary: Primary Series Cohort 2: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

Top of page

End point title

Primary Series Cohort 2: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. GMTRs were calculated as the ratio of GMTs post-vaccination (i.e., on Day 28) and pre-vaccination on Day 0. Results are based on the PPAS for Day 28 (2-dose) for primary series Cohort 2 Groups 4, 5 and 6.

End point type

Secondary

End point timeframe

Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination)

End point values	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®
Number of subjects analysed	342	120	124
Units: ratio
geometric mean (confidence interval 95%)	37.7 (34.0 to 41.8)	29.0 (24.4 to 34.6)	38.9 (32.4 to 46.7)

No statistical analyses for this end point

Secondary: Primary Series Cohort 1: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

Top of page

End point title

Primary Series Cohort 1: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

End point description

Virus neutralization was defined as complete (absence of fluorescent cells) and incomplete (presence of fluorescent cells) at the participant/timepoint level at the starting dilution (1/5) of RFFIT assay. Percentage of participants with determined complete and determined incomplete virus neutralization were reported. Results are based on the PPAS for Day 42 (3-dose) for primary series Cohort 1 Groups 1, 2 and 3. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Cohort 1: Day 0 (pre-vaccination), Day 28 and Day 42 (post-vaccination)

End point values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®
Number of subjects analysed	519	169	162
Units: percentage of participants
number (confidence interval 95%)
Day 0 - Complete neutralization: n=504, 166, 158	0.2 (0 to 1.1)	0.6 (0 to 3.3)	1.3 (0.2 to 4.5)
Day 0 - Incomplete neutralization: n=504, 166, 158	99.8 (98.9 to 100)	99.4 (96.7 to 100)	98.7 (95.5 to 99.8)
Day 28, Complete neutralization: n=514, 167, 161	100 (99.3 to 100)	99.4 (96.7 to 100)	99.4 (96.6 to 100)
Day 28, Incomplete neutralization: n=514, 167, 161	0 (0 to 0.7)	0.6 (0 to 3.3)	0.6 (0 to 3.4)
Day 42, Complete neutralization: n=518, 169, 161	100 (99.3 to 100)	99.4 (96.7 to 100)	100 (97.7 to 100)
Day 42, Incomplete neutralization: n=518, 169, 161	0 (0 to 0.7)	0.6 (0 to 3.3)	0 (0 to 2.3)

No statistical analyses for this end point

Secondary: Primary Series Cohort 2: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

Top of page

End point title

Primary Series Cohort 2: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

End point description

Virus neutralization was defined as complete (absence of fluorescent cells) and incomplete (presence of fluorescent cells) at the participant/timepoint level at the starting dilution (1/5) of RFFIT assay. Percentage of participants with determined complete and determined incomplete virus neutralization were reported. Results are based on the PPAS for Day 28 (2-dose) for primary series Cohort 2 Groups 4, 5 and 6. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Cohort 2: Day 0 (pre-vaccination) and Day 28 (post-vaccination)

End point values	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®
Number of subjects analysed	342	120	124
Units: percentage of participants
number (confidence interval 95%)
Day 0, Complete neutralization: n=330, 119, 117	0.9 (0.2 to 2.6)	4.2 (1.4 to 9.5)	0 (0 to 3.1)
Day 0, Incomplete neutralization: n=330, 119, 117	99.1 (97.4 to 99.8)	95.8 (90.5 to 98.6)	100 (96.9 to 100)
Day 28, Complete neutralization: n=339, 120, 124	100 (98.9 to 100)	100 (97.0 to 100)	98.4 (94.3 to 99.8)
Day 28, Incomplete neutralization: n=339, 120, 124	0 (0 to 1.1)	0 (0 to 3.0)	1.6 (0.2 to 5.7)

No statistical analyses for this end point

Secondary: Booster Phase: Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus

Top of page

End point title

Booster Phase: Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. Results are based on the PPAS for booster at Month 12 which included adult participants who received 3 injections of corresponding study vaccine in the primary series Cohort 1 and received a booster injection of VRVg-2 vaccine in the booster phase at Month 12, with no relevant protocol deviation before Month 12 + Day 14 (i.e., 14 days after the booster dose injection). Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Month 12 (pre-booster dose) and Month 12 + Day 14 (post-booster dose)

End point values	Booster Phase: Cohort-1 Group 1: VRVg-2 (Primed With VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® Primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)
Number of subjects analysed	80	26	28
Units: IU/mL
geometric mean (confidence interval 95%)
Month 12: n=80, 26, 28	0.679 (0.526 to 0.878)	0.540 (0.344 to 0.848)	0.487 (0.311 to 0.764)
Month 12 + 14 Days: n=80, 26, 28	56.5 (45.4 to 70.3)	57.1 (42.6 to 76.7)	33.7 (22.6 to 50.3)

No statistical analyses for this end point

Secondary: Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

Top of page

End point title

Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. Results are based on the PPAS for booster at Month 12. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Month 12 (pre-booster dose) and Month 12 + Day 14 (post-booster dose)

End point values	Booster Phase: Cohort-1 Group 1: VRVg-2 (Primed With VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® Primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)
Number of subjects analysed	80	26	28
Units: percentage of participants
number (confidence interval 95%)
Month 12: n=80, 26, 28	53.8 (42.2 to 65.0)	53.8 (33.4 to 73.4)	35.7 (18.6 to 55.9)
Month 12 + 14 days: n=80, 26, 28	100 (95.5 to 100)	100 (86.8 to 100)	100 (87.7 to 100)

No statistical analyses for this end point

Secondary: Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (LLOQ)

Top of page

End point title

Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (LLOQ)

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. LLOQ for the RFFIT assay was 0.2 IU/ mL. Results are based on the PPAS for booster at Month 12. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Month 12 (pre-booster dose) and Month 12 + Day 14 (post-booster dose)

End point values	Booster Phase: Cohort-1 Group 1: VRVg-2 (Primed With VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® Primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)
Number of subjects analysed	80	26	28
Units: percentage of participants
number (confidence interval 95%)
Month 12: n=80, 26, 28	86.3 (76.7 to 92.9)	76.9 (56.4 to 91.0)	85.7 (67.3 to 96.0)
Month 12 + 14 days: n=80, 26, 28	100 (95.5 to 100)	100 (86.8 to 100)	100 (87.7 to 100)

No statistical analyses for this end point

Secondary: Booster Phase: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

Top of page

End point title

Booster Phase: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. GMTRs were calculated as the ratio of GMTs post vaccination (i.e., on Month 12 and Month 12 + Day 14) and pre-vaccination on Day 0, pre-booster dose on Month 12. Results are based on the PPAS for booster at Month 12. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Day 0 (pre-vaccination), Month 12 (pre-booster dose) and Month 12 + Day 14 (post-booster dose)

End point values	Booster Phase: Cohort-1 Group 1: VRVg-2 (Primed With VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® Primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)
Number of subjects analysed	80	26	28
Units: ratio
geometric mean (confidence interval 95%)
Month 12/Day 0: n=80, 26, 28	6.79 (5.26 to 8.78)	5.40 (3.44 to 8.48)	4.78 (3.10 to 7.37)
Month 12+14 days/Day 0: n=80, 26, 28	565 (454 to 703)	571 (426 to 767)	331 (219 to 500)
Month 12+14 days/Month 12: n=80, 26, 28	83.2 (62.0 to 112)	106 (62.7 to 178)	69.2 (39.6 to 121)

No statistical analyses for this end point

Secondary: Booster Phase: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

Top of page

End point title

Booster Phase: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

End point description

Virus neutralization was defined as complete (absence of fluorescent cells) and incomplete (presence of fluorescent cells) at the participant/timepoint level at the starting dilution (1/5) of RFFIT assay. Percentage of participants with determined complete and determined incomplete virus neutralization were reported. Results are based on the PPAS for booster at Month 12. Here, 'number of subjects analyzed' = number of participants with available data for this outcome measure and ‘n’ = number of participants with available data for each specified category.

End point type

Secondary

End point timeframe

Month 12 (pre-booster dose) and Month (M) 12 + Day (D) 14 (post-booster dose)

End point values	Booster Phase: Cohort-1 Group 1: VRVg-2 (Primed With VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® Primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)
Number of subjects analysed	80	26	28
Units: percentage of participants
number (confidence interval 95%)
M12: - Complete neutralization: n=80, 26, 28	96.1 (89.0 to 99.2)	84.0 (63.9 to 95.5)	95.7 (78.1 to 99.9)
M12 - Incomplete neutralization: n=80, 26, 28	3.9 (0.8 to 11.0)	16.0 (4.5 to 36.1)	4.3 (0.1 to 21.9)
M12 + D14 - Complete neutralization: n=80, 26, 28	100 (95.5 to 100)	100 (86.8 to 100)	100 (87.2 to 100)
M12 + D14- Incomplete neutralization: n=80, 26, 28	0 (0 to 4.5)	0 (0 to 13.2)	0 (0 to 12.8)

No statistical analyses for this end point

Secondary: Number of Participants With Immediate Unsolicited Adverse Events (AEs)

Top of page

End point title

Number of Participants With Immediate Unsolicited Adverse Events (AEs)

End point description

An AE was defined as any untoward medical occurrence in a participant who received study vaccine and does not necessarily had to have a causal relationship with the treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset post-vaccination. All participants were observed for 30 minutes after any vaccination, and any unsolicited AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB. Results are based on the safety analysis set (SafAS) that included participants who had received at least one dose of the study vaccine and were analyzed according to the actual treatment received. The Booster Phase for Cohort-2 has not yet started, and data for that phase will be reported at time of final results posting.

End point type

Secondary

End point timeframe

Within 30 minutes after any vaccination

End point values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®	Booster Phase: Cohort-1 Group 1: VRVg-2 (primed with VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)
Number of subjects analysed	607	202	200	419	139	139	94	31	32
Units: participants	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Participants With Solicited Systemic Reactions

Top of page

End point title

Number of Participants With Solicited Systemic Reactions

End point description

A solicited systemic reaction (SR) was an expected AR observed and reported under conditions (nature & onset) pre-listed in the protocol and CRB and considered as related to vaccination. An AR was all noxious and unintended responses to a medicinal product related to any dose. Solicited systemic reactions included fever, vomiting, crying abnormal, drowsiness, appetite loss, irritability, headache, malaise and myalgia. Solicited systemic reactions were collected by different age groups: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability were collected for participants aged 12 to 23 months. Fever, Headache, Malaise and Myalgia were collected for participants aged >= 2 years. Results are based on the SafAS. Here, n= number of participants with available data for each specified category; 9999= no participants were analyzed. The Booster Phase for Cohort-2 has not yet started, and data for that phase will be reported at time of final results posting.

End point type

Secondary

End point timeframe

Within 7 Days after any vaccination.

End point values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®	Booster Phase: Cohort-1 Group 1: VRVg-2 (primed with VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)
Number of subjects analysed	607	202	200	419	139	139	94	31	32
Units: participants
Fever: n=606,201,200,419,139,139,94,31,32	50	11	4	2	0	0	0	0	0
Vomiting: n=17,2,2,0,0,0,0,0,0	4	1	1	9999	9999	9999	9999	9999	9999
Crying abnormal: n=17,2,2,0,0,0,0,0,0	8	0	1	9999	9999	9999	9999	9999	9999
Drowsiness: n=17,2,2,0,0,0,0,0,0	4	1	0	9999	9999	9999	9999	9999	9999
Appetite lost: n=17,2,2,0,0,0,0,0,0	3	1	0	9999	9999	9999	9999	9999	9999
Irritability: n=17,2,2,0,0,0,0,0,0	8	1	0	9999	9999	9999	9999	9999	9999
Headache: n=590,199,198,419,139,139,94,31,32	128	49	46	39	9	8	4	3	5
Malaise: n=590,199,198,419,139,139,94,31,32	161	45	48	37	10	12	8	3	7
Myalgia: n=590,199,198,419,139,139,94,31,32	249	66	78	78	12	29	23	9	15

No statistical analyses for this end point

Secondary: Number of Participants With Solicited Injection Site Reactions

Top of page

End point title

Number of Participants With Solicited Injection Site Reactions

End point description

A solicited reaction (SR) was an expected AR observed and reported under conditions (nature and onset) pre-listed (i.e., solicited) in the protocol and CRB and considered as related to vaccination. An AR was all noxious and unintended responses to a medicinal product related to any dose. Solicited injection site reactions included tenderness/pain, erythema and swelling. Results are based on the SafAS. The Booster Phase for Cohort-2 has not yet started, and data for that phase will be reported at time of final results posting.

End point type

Secondary

End point timeframe

Within 7 Days after any vaccination

End point values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®	Booster Phase: Cohort-1 Group 1: VRVg-2 (primed with VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)
Number of subjects analysed	607	202	200	419	139	139	94	31	32
Units: participants
Injection site tenderness/pain	344	95	106	111	30	43	44	12	17
Injection site erythema	24	6	6	0	0	1	0	0	0
Injection site swelling	14	4	13	1	0	1	0	1	0

No statistical analyses for this end point

Secondary: Number of Participants With Unsolicited Adverse Events

Top of page

End point title

Number of Participants With Unsolicited Adverse Events

End point description

End point type

Secondary

End point timeframe

Within 28 Days after any vaccination

End point values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®	Booster Phase: Cohort-1 Group 1: VRVg-2 (primed with VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)
Number of subjects analysed	607	202	200	419	139	139	94	31	32
Units: participants	137	45	40	44	18	12	13	3	5

No statistical analyses for this end point

Secondary: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

Top of page

End point title

Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

End point description

An SAEs was any untoward medical occurrence that at any dose resulted in death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect or a medically important event. An AESI was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. All SAEs and AESIs occurring during the study that were related to the product administered were reported by the Investigator to the Independent Ethics Committee/Institutional Review Board. Relatedness to study vaccine was based on Investigator's discretion. Results are based on the SafAS. The Booster Phase for Cohort-2 has not yet started, and data for that phase will be reported at time of final results posting.

End point type

Secondary

End point timeframe

From Baseline (Day 0) up to 6 months after last vaccination (i.e., up to 7 months for Primary Series Cohorts 1 & 2 and up to Month 18 for Booster Phase, Cohort 1)

End point values	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®	Primary Series: Cohort-2 Group 4: VRVg-2	Primary Series: Cohort-2 Group 5: Verorab®	Primary Series: Cohort-2 Group 6: Imovax Rabies®	Booster Phase: Cohort-1 Group 1: VRVg-2 (primed with VRVg-2)	Booster Phase: Cohort-1 Group 2: VRVg-2 (Verorab® primed)	Booster Phase:Cohort-1 Group 3: VRVg-2 (Imovax Rabies® Primed)
Number of subjects analysed	607	202	20	419	139	139	94	31	32
Units: participants
SAEs	10	3	5	0	0	0	2	0	1
AESIs	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

Primary series: From Baseline (Day 0) up to Month (M)7. Booster Phase Cohort 1: From the booster vaccination (M12) until M18.

Adverse event reporting additional description

Unsolicited AE: from D0 up to D28 post any vaccination. SR data: within 7 days post any vaccination. AE data are based on the SafAS. The booster phase of Cohort-2 has not yet started, and data for that phase will be reported at the time of final results posting. In the AE section, solicited reaction (SR), fever is reported as pyrexia.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

Primary Series: Cohort-1 Group 1: VRVg-2

Reporting group description

Pediatric and adult participants who received at least one dose of VRVg-2 vaccine in the primary series Cohort 1 Group 1 (on Day 0, Day 7 or Day 28).

Reporting group title

Primary Series: Cohort-1 Group 2: Verorab®

Reporting group description

Pediatric and adult participants who received at least one dose of Verorab® vaccine in the primary series Cohort 1 Group 2 (on Day 0, Day 7 or Day 28).

Reporting group title

Primary Series: Cohort-1 Group 3: Imovax Rabies®

Reporting group description

Pediatric and adult participants who received at least one dose of Imovax Rabies® vaccine in the primary series Cohort 1 Group 3 (on Day 0, Day 7 or Day 28).

Reporting group title

Primary Series: Cohort-2 Group 4: VRVg-2

Reporting group description

Adult participants who received at least one dose of VRVg-2 vaccine in the primary series Cohort 2 Group 4 (on Day 0 or Day 7).

Reporting group title

Cohort-1 Group 3: Imovax Rabies® (PrEP)/VRVg-2 (Booster)

Reporting group description

Reporting group title

Primary Series: Cohort-2 Group 6: Imovax Rabies®

Reporting group description

Adult participants who received at least one dose of Imovax Rabies® vaccine in the primary series Cohort 2 Group 6 (on Day 0 or Day 7).

Reporting group title

Cohort-1 Group 1: VRVg-2 (PrEP)/VRVg-2 (Booster)

Reporting group description

Reporting group title

Cohort-1 Group 2: Verorab® (PrEP)/VRVg-2 (Booster)

Reporting group description

Reporting group title

Primary Series: Cohort-2 Group 5: Verorab®

Reporting group description

Adult participants who received at least one dose of Verorab® vaccine in the primary series Cohort 2 Group 5 (on Day 0 or Day 7).

Serious adverse events	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®	Primary Series: Cohort-2 Group 4: VRVg-2	Cohort-1 Group 3: Imovax Rabies® (PrEP)/VRVg-2 (Booster)	Primary Series: Cohort-2 Group 6: Imovax Rabies®	Cohort-1 Group 1: VRVg-2 (PrEP)/VRVg-2 (Booster)	Cohort-1 Group 2: Verorab® (PrEP)/VRVg-2 (Booster)	Primary Series: Cohort-2 Group 5: Verorab®
Total subjects affected by serious adverse events
subjects affected / exposed	10 / 607 (1.65%)	3 / 202 (1.49%)	5 / 200 (2.50%)	0 / 419 (0.00%)	1 / 32 (3.13%)	0 / 139 (0.00%)	2 / 94 (2.13%)	0 / 31 (0.00%)	0 / 139 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Exposure To Communicable Disease
subjects affected / exposed	4 / 607 (0.66%)	0 / 202 (0.00%)	0 / 200 (0.00%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ligament Injury
subjects affected / exposed	0 / 607 (0.00%)	0 / 202 (0.00%)	1 / 200 (0.50%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Keratorhexis
subjects affected / exposed	0 / 607 (0.00%)	0 / 202 (0.00%)	1 / 200 (0.50%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intentional Overdose
subjects affected / exposed	0 / 607 (0.00%)	0 / 202 (0.00%)	1 / 200 (0.50%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Ectopic Pregnancy
subjects affected / exposed	0 / 607 (0.00%)	0 / 202 (0.00%)	0 / 200 (0.00%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	1 / 94 (1.06%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Imminent Abortion
subjects affected / exposed	0 / 607 (0.00%)	0 / 202 (0.00%)	1 / 200 (0.50%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Hemiplegia
subjects affected / exposed	0 / 607 (0.00%)	0 / 202 (0.00%)	0 / 200 (0.00%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	1 / 94 (1.06%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Food Allergy
subjects affected / exposed	0 / 607 (0.00%)	1 / 202 (0.50%)	0 / 200 (0.00%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal Pain
subjects affected / exposed	0 / 607 (0.00%)	1 / 202 (0.50%)	0 / 200 (0.00%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease
subjects affected / exposed	1 / 607 (0.16%)	0 / 202 (0.00%)	0 / 200 (0.00%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	0 / 607 (0.00%)	0 / 202 (0.00%)	0 / 200 (0.00%)	0 / 419 (0.00%)	1 / 32 (3.13%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 607 (0.16%)	0 / 202 (0.00%)	1 / 200 (0.50%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Croup Infectious
subjects affected / exposed	1 / 607 (0.16%)	0 / 202 (0.00%)	0 / 200 (0.00%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dengue Fever
subjects affected / exposed	1 / 607 (0.16%)	0 / 202 (0.00%)	0 / 200 (0.00%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	1 / 607 (0.16%)	0 / 202 (0.00%)	0 / 200 (0.00%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infectious Mononucleosis
subjects affected / exposed	1 / 607 (0.16%)	0 / 202 (0.00%)	0 / 200 (0.00%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rhinovirus Infection
subjects affected / exposed	0 / 607 (0.00%)	1 / 202 (0.50%)	0 / 200 (0.00%)	0 / 419 (0.00%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Primary Series: Cohort-1 Group 1: VRVg-2	Primary Series: Cohort-1 Group 2: Verorab®	Primary Series: Cohort-1 Group 3: Imovax Rabies®	Primary Series: Cohort-2 Group 4: VRVg-2	Cohort-1 Group 3: Imovax Rabies® (PrEP)/VRVg-2 (Booster)	Primary Series: Cohort-2 Group 6: Imovax Rabies®	Cohort-1 Group 1: VRVg-2 (PrEP)/VRVg-2 (Booster)	Cohort-1 Group 2: Verorab® (PrEP)/VRVg-2 (Booster)	Primary Series: Cohort-2 Group 5: Verorab®
Total subjects affected by non serious adverse events
subjects affected / exposed	414 / 607 (68.20%)	121 / 202 (59.90%)	128 / 200 (64.00%)	130 / 419 (31.03%)	18 / 32 (56.25%)	48 / 139 (34.53%)	48 / 94 (51.06%)	15 / 31 (48.39%)	34 / 139 (24.46%)
Nervous system disorders
Headache
subjects affected / exposed	130 / 607 (21.42%)	50 / 202 (24.75%)	47 / 200 (23.50%)	40 / 419 (9.55%)	7 / 32 (21.88%)	8 / 139 (5.76%)	4 / 94 (4.26%)	3 / 31 (9.68%)	10 / 139 (7.19%)
occurrences all number	178	66	62	46	7	9	4	3	14
General disorders and administration site conditions
Injection Site Pain
subjects affected / exposed	344 / 607 (56.67%)	95 / 202 (47.03%)	106 / 200 (53.00%)	111 / 419 (26.49%)	17 / 32 (53.13%)	43 / 139 (30.94%)	44 / 94 (46.81%)	12 / 31 (38.71%)	30 / 139 (21.58%)
occurrences all number	655	158	191	167	17	63	44	12	41
Malaise
subjects affected / exposed	161 / 607 (26.52%)	45 / 202 (22.28%)	48 / 200 (24.00%)	37 / 419 (8.83%)	7 / 32 (21.88%)	12 / 139 (8.63%)	8 / 94 (8.51%)	3 / 31 (9.68%)	10 / 139 (7.19%)
occurrences all number	229	57	79	43	7	16	8	3	14
Injection Site Swelling
subjects affected / exposed	14 / 607 (2.31%)	4 / 202 (1.98%)	13 / 200 (6.50%)	1 / 419 (0.24%)	0 / 32 (0.00%)	1 / 139 (0.72%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences all number	19	4	18	2	0	1	0	0	0
Pyrexia
subjects affected / exposed	51 / 607 (8.40%)	12 / 202 (5.94%)	5 / 200 (2.50%)	3 / 419 (0.72%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences all number	54	12	5	3	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Myalgia
subjects affected / exposed	249 / 607 (41.02%)	67 / 202 (33.17%)	79 / 200 (39.50%)	78 / 419 (18.62%)	15 / 32 (46.88%)	30 / 139 (21.58%)	24 / 94 (25.53%)	9 / 31 (29.03%)	12 / 139 (8.63%)
occurrences all number	405	103	135	103	15	38	24	9	17
Infections and infestations
Nasopharyngitis
subjects affected / exposed	27 / 607 (4.45%)	9 / 202 (4.46%)	12 / 200 (6.00%)	3 / 419 (0.72%)	0 / 32 (0.00%)	0 / 139 (0.00%)	0 / 94 (0.00%)	0 / 31 (0.00%)	0 / 139 (0.00%)
occurrences all number	27	9	14	3	0	0	0	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

05 Nov 2021

Protocol amendment-2 was developed to conservatively adjust the estimation of seroconversion rate at Day (D)28 for adults subjects in VRVg-2 and the control vaccines from 99% to 96.5% according to the latest results from VAJ00001 study and to ensure the statistical power of the secondary objective to demonstrate that VRVg-2 is non-inferior to Verorab and Imovax Rabies vaccines in each age group (pediatric and adult population), in terms of proportion of subjects achieving an RVNA titer ≥0.5 IU/mL at D28 based on the above-adjusted estimation. Protocol amendment 2 also incorporated a single booster between 2 and up to 3 years with a new batch of VRVg-2 as recommended in the new Advisory Committee on Immunization Practices (ACIP) 2021 guidelines.

31 May 2022

Protocol amendment-3 added a secondary objective to demonstrate the acceptability of the immune response at D28 of a 1-week 2-dose pre-exposure prophylaxis (PrEP) regimen. It also added the evaluation of persistence of the immune response at Month (M)6, M12, M18 and pre-booster between M24 up to M36 after a 2-dose primary series in the subset of adults who are randomized to be part of the Immunogenicity Persistence and Booster Phase Cohort 2.

17 Nov 2022

Protocol amendment-4: As stated in Section 1.3.1 (Potential Benefits to Subjects) of the protocol, most of the subjects were expected to have reached RVNA titers ≥0.5 IU/mL after the completion of the 2- or 3-dose PrEP regimen of rabies vaccine (and booster dose for adult subsets). Depending on Investigator’s clinical judgment, subjects with RVNA titers <0.5 IU/mL at all timepoints, might be offered an additional injection of a local licensed rabies vaccine chosen by the Investigator and administered according to the local summaries of product characteristics (SmPC)/product label (PI) or national guidelines and if the subject / subject’s legally acceptable representative (LAR) agreed. Such vaccine was offered outside of the scope of the protocol (i.e., no safety nor immunogenicity data were collected after this vaccine injection), free of charge at the study site. This was the Investigator's responsibility to decide which vaccine was the most appropriate for giving real benefit to the subject. Moreover, Section-5.2.9 (conditions for withdrawal) of the protocol was updated to avoid any unnecessary subjects’ withdrawal due to missing visits (at M6, M12, and/or M18) during the Immunogenicity Persistence and Booster Phase Cohort 2 (adult subset). Section-6.7 (randomization and allocation procedures) of the protocol was updated to clarify the subject number assigning rule was different between Cohort 1 and Cohort 2, due to different interactive response technology (IRT) settings.

12 Jun 2023

Protocol amendment-5 added 2 secondary objectives to demonstrate the non-inferiority (NI) of a 2-dose VRVg-2 PrEP at D28 versus 3-dose Imovax Rabies PrEP at D42 in each age group, and also to demonstrate NI of 2-dose Imovax Rabies PrEP at D28 versus 3-dose Imovax Rabies PrEP at D42 in each age group, both with a NI margin of -10%for each of these 2 new secondary objectives.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 IU/mL

Primary: Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 IU/mL

Secondary: Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

Secondary: Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

Secondary: Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population

Secondary: Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population

Secondary: Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population (Groups 1 and 4) Versus Cohort 1: Group 3: Non-inferiority Analysis

Secondary: Primary Series: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population (Groups 1 and 4) Versus Cohort 1: Group 3: Non-inferiority Analysis

Secondary: Primary Series: Groups 1 and 4: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population - Superiority Analysis

Secondary: Primary Series: Groups 1 and 4: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Pooled Population - Superiority Analysis

Secondary: Primary Series Cohort 1 Group 3: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Non-Inferiority Analysis

Secondary: Primary Series Cohort 1 Group 3: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL - Non-Inferiority Analysis

Secondary: Primary Series Cohort 1: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus

Secondary: Primary Series Cohort 1: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus

Secondary: Primary Series Cohort 2: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus

Secondary: Primary Series Cohort 2: Rabies Virus Neutralizing Antibody Geometric Mean Titers (GMTs) Against Rabies Virus

Secondary: Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

Secondary: Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

Secondary: Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

Secondary: Primary Series Cohort 1: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

Secondary: Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

Secondary: Primary Series Cohort 2: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

Secondary: Primary Series Cohort 1: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

Secondary: Primary Series Cohort 1: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

Secondary: Primary Series Cohort 2: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

Secondary: Primary Series Cohort 2: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

Secondary: Primary Series Cohort 1: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

Secondary: Primary Series Cohort 1: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

Secondary: Primary Series Cohort 2: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

Secondary: Primary Series Cohort 2: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

Secondary: Booster Phase: Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus

Secondary: Booster Phase: Rabies Virus Neutralizing Antibody (RVNA) Geometric Mean Titers (GMTs) Against Rabies Virus

Secondary: Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

Secondary: Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.5 IU/mL

Secondary: Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (LLOQ)

Secondary: Booster Phase: Percentage of Participants With Rabies Virus Neutralizing Antibody Titers >=0.2 IU/mL (LLOQ)

Secondary: Booster Phase: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

Secondary: Booster Phase: Geometric Mean Titer Ratio (GMTR) of Rabies Virus Neutralizing Antibody Titers

Secondary: Booster Phase: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

Secondary: Booster Phase: Percentage of Participants With Determined Complete and Determined Incomplete Virus Neutralization

Secondary: Number of Participants With Immediate Unsolicited Adverse Events (AEs)

Secondary: Number of Participants With Immediate Unsolicited Adverse Events (AEs)

Secondary: Number of Participants With Solicited Systemic Reactions

Secondary: Number of Participants With Solicited Systemic Reactions

Secondary: Number of Participants With Solicited Injection Site Reactions

Secondary: Number of Participants With Solicited Injection Site Reactions

Secondary: Number of Participants With Unsolicited Adverse Events

Secondary: Number of Participants With Unsolicited Adverse Events

Secondary: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

Secondary: Number of Participants With Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information