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

Summary
EudraCT number	2019-004008-36
Trial protocol	Outside EU/EEA
Global end of trial date	21 Jul 2022

Results information
Results version number	v1(current)
This version publication date	01 Feb 2023
First version publication date	01 Feb 2023
Other versions

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

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Trial information

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Sponsor protocol code

VRV09

ISRCTN number

US NCT number

NCT04478084

WHO universal trial number (UTN)

U1111-1227-4143

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

Final

Date of interim/final analysis

10 Sep 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

21 Jul 2022

Was the trial ended prematurely?

Main objective of the trial

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

Protection of trial subjects

Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment were also available on site in case of any immediate allergic reactions.

Background therapy

Evidence for comparator

Actual start date of recruitment

04 Aug 2020

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Thailand: 402

Worldwide total number of subjects

402

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)

Adolescents (12-17 years)

Adults (18-64 years)

229

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

The study was conducted at 3 active sites in Thailand between 04 August 2020 and 21 July 2022.

Screening details

A total of 402 subjects were enrolled and randomised in the study. Subjects received vaccination during the active phase of the study on Days 0, 3, 7 and 28 and were followed-up for safety 6-months post-vaccination.

Period 1 title

Overall study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Carer, Assessor

Are arms mutually exclusive

Yes

Group 1: VRVg-2

Arm description

Pediatric subjects aged 1 year to less than (<) 18 years received 8 injections (1 vaccination on each arm) of 0.5 mililitres (mL) of VRVg-2 intradermally on Days 0, 3, 7 and 28.

Arm type

Experimental

Investigational medicinal product name

Purified vero rabies vaccine - serum free

Investigational medicinal product code

Other name

VRVg-2

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intradermal use

Dosage and administration details

8 injections (1 vaccination on each arm) intradermally at Days 0, 3, 7, and 28.

Group 2: Verorab®

Arm description

Pediatric subjects aged 1 year to <18 years received 8 injections (1 vaccination on each arm) of 0.5 mL purified inactivated rabies vaccine prepared on Vero cell line (Verorab®) intradermally on Days 0, 3, 7 and 28.

Arm type

Active comparator

Investigational medicinal product name

Purified inactivated rabies vaccine

Investigational medicinal product code

Other name

Verorab®

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intradermal use

Dosage and administration details

8 injections (1 vaccination on each arm) intradermally at Days 0, 3, 7, and 28.

Group 3: VRVg-2 + ERIG

Arm description

Adult subjects aged 18 year and above received 6 injections (1 vaccination on each arm) of 0.5 mL VRVg-2 intradermally on Days 0, 3 and 7 along with Equine rabies immunoglobulins (ERIG) intramuscular (IM) injection at Day 0.

Arm type

Experimental

Investigational medicinal product name

Purified vero rabies vaccine - serum free

Investigational medicinal product code

Other name

VRVg-2

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intradermal use

Dosage and administration details

6 injections (1 vaccination on each arm) intradermally at Days 0, 3 and 7.

Investigational medicinal product name

Equine rabies immunoglobulins

Investigational medicinal product code

Other name

ERIG

Pharmaceutical forms

Solution for injection in vial

Routes of administration

Intramuscular use

Dosage and administration details

Single 0.5 mL IM injection at Day 0.

Group 4: Verorab® + ERIG

Arm description

Adult subjects aged 18 year and above received 6 injections (1 vaccination on each arm) of 0.5 mL Verorab® intradermally on Days 0, 3 and 7 along with ERIG IM injection at Day 0.

Arm type

Active comparator

Investigational medicinal product name

Purified inactivated rabies vaccine

Investigational medicinal product code

Other name

Verorab®

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intradermal use

Dosage and administration details

6 injections (1 vaccination on each arm) intradermally at Days 0, 3 and 7.

Investigational medicinal product name

Equine rabies immunoglobulins

Investigational medicinal product code

Other name

ERIG

Pharmaceutical forms

Solution for injection in vial

Routes of administration

Intramuscular use

Dosage and administration details

Single 0.5 mL IM injection at Day 0.

Group 5: VRVg-2 + HRIG

Arm description

Adult subjects aged 18 year and above received 8 injections (1 vaccination on each arm) of 0.5 mL VRVg-2 intradermally on Days 0, 3, 7, and 28 along with HRIG IM injection at Day 0.

Arm type

Experimental

Investigational medicinal product name

Purified vero rabies vaccine - serum free

Investigational medicinal product code

Other name

VRVg-2

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intradermal use

Dosage and administration details

8 injections (1 vaccination on each arm) intradermally at Days 0, 3, 7, and 28.

Investigational medicinal product name

Human rabies immunoglobulins

Investigational medicinal product code

Other name

IMOGAM® Rabies-HT, HRIG

Pharmaceutical forms

Solution for injection in vial

Routes of administration

Intramuscular use

Dosage and administration details

Single 0.5 mL IM injection at Day 0.

Group 6: Verorab + HRIG

Arm description

Adult subjects aged 18 year and above received 8 injections (1 vaccination on each arm) of 0.5 mL Verorab® intradermally on Days 0, 3, 7, and 28 along with HRIG IM injection at Day 0.

Arm type

Active comparator

Investigational medicinal product name

Purified inactivated rabies vaccine

Investigational medicinal product code

Other name

Verorab®

Pharmaceutical forms

Powder for solution for injection

Routes of administration

Intradermal use

Dosage and administration details

8 injections (1 vaccination on each arm) intradermally at Days 0, 3, 7, and 28.

Investigational medicinal product name

Human rabies immunoglobulins

Investigational medicinal product code

Other name

IMOGAM® Rabies-HT, HRIG

Pharmaceutical forms

Solution for injection in vial

Routes of administration

Intramuscular use

Dosage and administration details

Single 0.5 mL IM injection at Day 0.

Number of subjects in period 1	Group 1: VRVg-2	Group 2: Verorab®	Group 3: VRVg-2 + ERIG	Group 4: Verorab® + ERIG	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Started	112	56	26	14	129	65
Vaccination 1 (Day 0)	112	56	26	14	129	65
Vaccination 2 (Day 3)	112	56	23	14	129	65
Vaccination 3 (Day 7)	112	56	21	12	129	65
Vaccination 4 (Day 28)	112	56	0	0	127	64
Completed	112	56	0	0	114	54
Not completed	0	0	26	14	15	11
Adverse event	-	-	6	2	-	-
Protocol deviation	-	-	20	12	15	11

Baseline characteristics

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Reporting group title

Group 1: VRVg-2

Reporting group description

Pediatric subjects aged 1 year to less than (<) 18 years received 8 injections (1 vaccination on each arm) of 0.5 mililitres (mL) of VRVg-2 intradermally on Days 0, 3, 7 and 28.

Reporting group title

Group 2: Verorab®

Reporting group description

Reporting group title

Group 3: VRVg-2 + ERIG

Reporting group description

Reporting group title

Group 4: Verorab® + ERIG

Reporting group description

Adult subjects aged 18 year and above received 6 injections (1 vaccination on each arm) of 0.5 mL Verorab® intradermally on Days 0, 3 and 7 along with ERIG IM injection at Day 0.

Reporting group title

Group 5: VRVg-2 + HRIG

Reporting group description

Adult subjects aged 18 year and above received 8 injections (1 vaccination on each arm) of 0.5 mL VRVg-2 intradermally on Days 0, 3, 7, and 28 along with HRIG IM injection at Day 0.

Reporting group title

Group 6: Verorab + HRIG

Reporting group description

Adult subjects aged 18 year and above received 8 injections (1 vaccination on each arm) of 0.5 mL Verorab® intradermally on Days 0, 3, 7, and 28 along with HRIG IM injection at Day 0.

Reporting group values	Group 1: VRVg-2	Group 2: Verorab®	Group 3: VRVg-2 + ERIG	Group 4: Verorab® + ERIG	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG	Total
Number of subjects	112	56	26	14	129	65	402
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	10.1 ± 4.3	10.8 ± 3.8	36.2 ± 10.4	37.3 ± 11.1	40.2 ± 11.1	39.2 ± 10.9	-
Gender categorical
Units: Subjects
Female	54	24	18	9	78	39	222
Male	58	32	8	5	51	26	180

End points

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Reporting group title

Group 1: VRVg-2

Reporting group description

Pediatric subjects aged 1 year to less than (<) 18 years received 8 injections (1 vaccination on each arm) of 0.5 mililitres (mL) of VRVg-2 intradermally on Days 0, 3, 7 and 28.

Reporting group title

Group 2: Verorab®

Reporting group description

Reporting group title

Group 3: VRVg-2 + ERIG

Reporting group description

Reporting group title

Group 4: Verorab® + ERIG

Reporting group description

Adult subjects aged 18 year and above received 6 injections (1 vaccination on each arm) of 0.5 mL Verorab® intradermally on Days 0, 3 and 7 along with ERIG IM injection at Day 0.

Reporting group title

Group 5: VRVg-2 + HRIG

Reporting group description

Adult subjects aged 18 year and above received 8 injections (1 vaccination on each arm) of 0.5 mL VRVg-2 intradermally on Days 0, 3, 7, and 28 along with HRIG IM injection at Day 0.

Reporting group title

Group 6: Verorab + HRIG

Reporting group description

Adult subjects aged 18 year and above received 8 injections (1 vaccination on each arm) of 0.5 mL Verorab® intradermally on Days 0, 3, 7, and 28 along with HRIG IM injection at Day 0.

Primary: Percentage of Subjects With Rabies Virus Neutralising Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 International Units per Mililitres (IU/mL)

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End point title

Percentage of Subjects With Rabies Virus Neutralising Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 International Units per Mililitres (IU/mL) ^[1] ^[2]

End point description

RVNA titer against rabies virus was assessed using the Rapid Fluorescent Focus Inhibition test (RFFIT) assay method. Analysis was performed on the per-protocol analysis set (PPAS) that included all subjects who received at least 1 dose of the study vaccine. The subjects who presented protocol deviations and met PPAS exclusion criteria were excluded from PPAS. Here, 'n' = subjects with available data for each specified category.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination), Day 14 and Day 42 (post-vaccination)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistical analysis was reported for the endpoint.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint is reporting data for applicable arms in the study.

End point values	Group 1: VRVg-2	Group 2: Verorab®	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Number of subjects analysed	98	52	78	37
Units: percentage of subjects
number (confidence interval 95%)
Day 0 (n=98,52,78,37)	0.0 (0.0 to 3.7)	0.0 (0.0 to 6.8)	0.0 (0.0 to 4.6)	0.0 (0.0 to 9.5)
Day 14 (n=97,49,74,36)	100 (96.3 to 100)	98.0 (89.1 to 99.9)	59.5 (47.4 to 70.7)	52.8 (35.5 to 69.6)
Day 42 (n=98,52,78,37)	100 (96.3 to 100)	100 (93.2 to 100)	96.2 (89.2 to 99.2)	100 (90.5 to 100)

No statistical analyses for this end point

Primary: Percentage of Subjects With RVNA Titer >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

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End point title

Percentage of Subjects With RVNA Titer >=0.2 IU/mL (Lower Limit of Quantification [LLOQ]) ^[3] ^[4]

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. Analysis was performed on PPAS population. Here 'n'= subjects with available data for each specified category.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination), Day 14 and Day 42 (post-vaccination)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistical analysis was reported for the endpoint.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint is reporting data for applicable arms in the study.

End point values	Group 1: VRVg-2	Group 2: Verorab®	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Number of subjects analysed	98	52	78	37
Units: percentage of subjects
number (confidence interval 95%)
Day 0 (n=98,52,78,37)	0.0 (0.0 to 3.7)	0.0 (0.0 to 6.8)	0.0 (0.0 to 4.6)	0.0 (0.0 to 9.5)
Day 14 (n=97,49,74,36)	100 (96.3 to 100)	100 (92.7 to 100)	85.1 (75.0 to 92.3)	83.3 (67.2 to 93.6)
Day 42 (n=98,52,78,37)	100 (96.3 to 100)	100 (93.2 to 100)	98.7 (93.1 to 100)	100 (90.5 to 100)

No statistical analyses for this end point

Primary: Geometric Mean Titer Ratios (GMTRs) of Individual RVNA Titers

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End point title

Geometric Mean Titer Ratios (GMTRs) of Individual RVNA Titers ^[5] ^[6]

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 14 and Day 42) and pre-vaccination on Day 0. Analysis was performed on PPAS population. Here, 'n' = subjects with available data for each specified category.

End point type

Primary

End point timeframe

Day 0 (pre-vaccination), Day 14 and Day 42 (post-vaccination)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistical analysis was reported for the endpoint.
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint is reporting data for applicable arms in the study.

End point values	Group 1: VRVg-2	Group 2: Verorab®	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Number of subjects analysed	98	52	78	37
Units: ratio
geometric mean (confidence interval 95%)
Day 14/ Day 0 (n=97,49,74,36)	29.4 (24.8 to 34.9)	25.3 (19.7 to 32.6)	6.77 (5.21 to 8.79)	5.39 (3.65 to 7.96)
Day 42/Day 0 (n=98,52,78,37)	114 (96.4 to 134)	96.2 (79.5 to 116)	31.3 (24.9 to 39.2)	44.1 (33.1 to 58.7)

No statistical analyses for this end point

Secondary: Percentage of Subjects With RVNA Titer >= 0.5 IU/mL: Group 3 and Group 4

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End point title

Percentage of Subjects With RVNA Titer >= 0.5 IU/mL: Group 3 and Group 4 ^[7]

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. Analysis was performed on PPAS population.

End point type

Secondary

End point timeframe

Day 0 (pre-vaccination) and Day 14 (post-vaccination)

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint is reporting data for applicable arms in the study.

End point values	Group 3: VRVg-2 + ERIG	Group 4: Verorab® + ERIG
Number of subjects analysed	16	9
Units: percentage of subjects
number (confidence interval 95%)
Day 0	0.0 (0.0 to 20.6)	0.0 (0.0 to 33.6)
Day 14	75.0 (47.6 to 92.7)	55.6 (21.2 to 86.3)

No statistical analyses for this end point

Secondary: Percentage of Subjects With RVNA Titer >= 0.2 IU/mL (LLOQ): Group 3 and Group 4

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End point title

Percentage of Subjects With RVNA Titer >= 0.2 IU/mL (LLOQ): Group 3 and Group 4 ^[8]

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. Analysis was performed on PPAS population.

End point type

Secondary

End point timeframe

Day 0 (pre-vaccination) and Day 14 (post-vaccination)

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint is reporting data for applicable arms in the study.

End point values	Group 3: VRVg-2 + ERIG	Group 4: Verorab® + ERIG
Number of subjects analysed	16	9
Units: percentage of subjects
number (confidence interval 95%)
Day 0	0.0 (0.0 to 20.6)	0.0 (0.0 to 33.6)
Day 14	100 (79.4 to 100)	77.8 (40.0 to 97.2)

No statistical analyses for this end point

Secondary: GMTRs of Individual RVNA Titers: Group 3 and Group 4

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End point title

GMTRs of Individual RVNA Titers: Group 3 and Group 4 ^[9]

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 14) and pre-vaccination on Day 0. Analysis was performed on PPAS population.

End point type

Secondary

End point timeframe

Day 0 (pre-vaccination) and Day 14 (post-vaccination)

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint is reporting data for applicable arms in the study.

End point values	Group 3: VRVg-2 + ERIG	Group 4: Verorab® + ERIG
Number of subjects analysed	16	9
Units: ratio
geometric mean (confidence interval 95%)
Day 14/Day 0	10.1 (6.17 to 16.4)	13.6 (1.98 to 92.9)

No statistical analyses for this end point

Secondary: Percentage of Subjects With RVNA Titer >= 0.5 IU/mL: Groups 1, 2, 5 and 6

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End point title

Percentage of Subjects With RVNA Titer >= 0.5 IU/mL: Groups 1, 2, 5 and 6 ^[10]

End point description

RVNA titer against rabies virus was assessed using the RFFIT assay method. Analysis was performed on PPAS population. Here, 'number analysed' = subjects with available data for this endpoint. Data for this endpoint was not planned to be collected and analysed for Groups 3 and 4.

End point type

Secondary

End point timeframe

Day 90 (post-vaccination)

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint is reporting data for applicable arms in the study.

End point values	Group 1: VRVg-2	Group 2: Verorab®	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Number of subjects analysed	97	52	76	37
Units: percentage of subjects
number (confidence interval 95%)	99.0 (94.4 to 100)	98.1 (89.7 to 100)	75.0 (63.7 to 84.2)	78.4 (61.8 to 90.2)

No statistical analyses for this end point

Secondary: Percentage of Subjects With RVNA Titer >= 0.2 IU/mL (LLOQ): Groups 1, 2, 5 and 6

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End point title

Percentage of Subjects With RVNA Titer >= 0.2 IU/mL (LLOQ): Groups 1, 2, 5 and 6 ^[11]

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. Analysis was performed on PPAS population. Here, 'number analysed' = subjects with available data for this endpoint. Data for this endpoint was not planned to be collected and analysed for Groups 3 and 4.

End point type

Secondary

End point timeframe

Day 90 (post-vaccination)

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint is reporting data for applicable arms in the study.

End point values	Group 1: VRVg-2	Group 2: Verorab®	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Number of subjects analysed	97	52	76	37
Units: percentage of subjects
number (confidence interval 95%)	100 (96.3 to 100)	100 (93.2 to 100)	88.2 (78.7 to 94.4)	94.6 (81.8 to 99.3)

No statistical analyses for this end point

Secondary: GMTRs of Individual RVNA Titers: Groups 1, 2, 5 and 6

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End point title

GMTRs of Individual RVNA Titers: Groups 1, 2, 5 and 6 ^[12]

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 90) and pre-vaccination on Day 0. Analysis was performed on PPAS population. Here, 'number analysed' = subjects with available data for this endpoint. Data for this endpoint was not planned to be collected and analysed for Groups 3 and 4.

End point type

Secondary

End point timeframe

Day 0 (pre-vaccination) and Day (90 post-vaccination)

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Endpoint is reporting data for applicable arms in the study.

End point values	Group 1: VRVg-2	Group 2: Verorab®	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Number of subjects analysed	97	52	76	37
Units: ratio
geometric mean (confidence interval 95%)
Day 90/Day 0	30.3 (25.6 to 36.0)	22.3 (18.5 to 26.7)	7.70 (6.08 to 9.73)	9.58 (6.92 to 13.2)

No statistical analyses for this end point

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

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End point title

Number of Subjects With Immediate Unsolicited Systemic Adverse Events (AEs)

End point description

An AE was defined as any untoward medical occurrence in a subject who received study vaccine and does not necessarily had to have a causal relationship with 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 subjects 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. Analysis was performed on the safety analysis set (SafAS) that included subjects who had received at least one dose of the study vaccine and were analysed according to the actual study vaccine they received and after any dose according to the study vaccine received at the first dose. Reported AEs were presented for each arm as pre-specified in the protocol.

End point type

Secondary

End point timeframe

Within 30 minutes post-any vaccination

End point values	Group 1: VRVg-2	Group 2: Verorab®	Group 3: VRVg-2 + ERIG	Group 4: Verorab® + ERIG	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Number of subjects analysed	112	56	26	14	129	65
Units: subjects	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Solicited Injection Site Reactions

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End point title

Number of Subjects With Solicited Injection Site Reactions

End point description

A solicited reaction (SR) was an expected adverse reaction (AR) observed and reported under conditions (nature and onset) prelisted (i.e., solicited) in the protocol and CRB and considered as related to vaccination (vacc). An AR was all noxious and unintended responses to a medicinal product related to any dose. Solicited injection site reactions included pain, erythema and swelling at and around the injection site. Analysis was performed on SafAS. Here, 'n' = subjects with available data for each specified category. Here, "99999" is used as a space filler and denotes that no subjects were available for analysis for the specified category at each specified timepoint. Reported AEs were presented for each arm as pre-specified in the protocol.

End point type

Secondary

End point timeframe

Within 7 days post any and each vaccination (Vaccination 1 [Day 0], 2 [Day 3], 3 [Day 7] and 4 [Day 28])

End point values	Group 1: VRVg-2	Group 2: Verorab®	Group 3: VRVg-2 + ERIG	Group 4: Verorab® + ERIG	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Number of subjects analysed	112	56	26	14	129	65
Units: subjects
Pain Post-any vacc. (n=112,56,26,14,129,65)	44	23	14	5	57	30
Pain Post-vacc. 1 (n=112,56,26,14,129,65)	30	19	13	4	35	20
Pain Post-vacc. 2 (n=112,56,23,14,129,65)	33	16	4	1	25	11
Pain Post-vacc. 3 (n=112,56,21,12,129,65)	23	6	2	2	31	13
Pain Post-vacc. 4 (n=112,56,0,0,127,64)	18	8	99999	99999	24	12
Erythema Post-any vacc. (n=112,56,26,14,129,65)	40	15	0	0	0	2
Erythema Post-vacc. 1 (n=112,56,26,14,129,65)	20	8	0	0	0	0
Erythema Post-vacc. 2 (n=112,56,23,14,129,65)	22	10	0	0	0	1
Erythema Post-vacc. 3 (n=112,56,21,12,129,65)	23	11	0	0	0	0
Erythema Post-vacc. 4 (n=112,56,0,0,127,64)	31	12	99999	99999	0	1
Swelling Post-any vacc. (n=112,56,26,14,129,65)	53	27	0	0	0	0
Swelling Post-vacc. 1 (n=112,56,26,14,129,65)	28	10	0	0	0	0
Swelling Post-vacc. 2 (n=112,56,23,14,129,65)	32	18	0	0	0	0
Swelling Post-vacc. 3 (n=112,56,21,12,129,65)	41	20	0	0	0	0
Swelling Post-vacc. 4 (n=112,56,0,0,127,64)	46	21	99999	99999	0	0

No statistical analyses for this end point

Secondary: Number of Subjects With Solicited Systemic Reactions

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End point title

Number of Subjects With Solicited Systemic Reactions

End point description

SR: expected AR observed and reported under conditions (nature and onset) prelisted (i.e., solicited) in protocol and CRB and considered as related to vaccination. Solicited reactions were collected for different age groups: fever, vomiting, crying abnormal, drowsiness, appetite lost and irritability were collected for subjects aged 12 to 23 months and fever, headache, malaise and myalgia were collected for subjects aged >= 2 years. Solicited systemic reactions were analysed between each vaccination if vaccinations are separated less than 7 days, and up to 7 days after each vaccination if vaccinations were separated by 7 days or more. Analysis was performed on SafAS. Here, 'n' = subjects with available data for each specified category. Here, "99999" is used as a space filler and denotes that no subjects were available for analysis for the specified category at each specified timepoint. Reported AEs were presented for each arm as pre-specified in protocol.

End point type

Secondary

End point timeframe

Within 7 days post any and each vaccination (Vaccination 1 [Day 0], 2 [Day 3], 3 [Day 7] and 4 [Day 28])

End point values	Group 1: VRVg-2	Group 2: Verorab®	Group 3: VRVg-2 + ERIG	Group 4: Verorab® + ERIG	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Number of subjects analysed	112	56	26	14	129	65
Units: subjects
Fever Post-any Vacc. (n=112,56,26,14,129,65)	1	0	2	0	2	2
Fever Post-vacc. 1 (n=112,56,26,14,129,65)	0	0	0	0	0	0
Fever Post-vacc. 2 (n=112,56,23,14,129,65)	1	0	0	0	0	0
Fever Post-vacc. 3 (n=112,56,21,12,129,65)	0	0	2	0	0	0
Fever Post-vacc. 4 (n=112,56,0,0,127,64)	0	0	99999	99999	2	2
Vomiting Post-any Vacc. (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Vomiting Post-vacc. 1 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Vomiting Post-vacc. 2 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Vomiting Post-vacc. 3 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Vomiting Post-vacc. 4 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Crying abnormal Post-any Vacc. (n=2,1,0,0,0,0)	1	0	99999	99999	99999	99999
Crying abnormal Post-vacc. 1 (n=2,1,0,0,0,0)	1	0	99999	99999	99999	99999
Crying abnormal Post-vacc. 2 (n=2,1,0,0,0,0)	1	0	99999	99999	99999	99999
Crying abnormal Post-vacc. 3 (n=2,1,0,0,0,0)	1	0	99999	99999	99999	99999
Crying abnormal Post-vacc. 4 (n=2,1,0,0,0,0)	1	0	99999	99999	99999	99999
Drowsiness Post-any Vacc. (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Drowsiness Post-vacc. 1 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Drowsiness Post-vacc. 2 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Drowsiness Post-vacc. 3 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Drowsiness Post-vacc. 4 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Appetite lost Post-any Vacc. (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Appetite lost Post-vacc. 1 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Appetite lost Post-vacc. 2 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Appetite lost Post-vacc. 3 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Appetite lost Post-vacc. 4 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Irritability Post-any Vacc. (n=2,1,0,0,0,0)	1	0	99999	99999	99999	99999
Irritability Post-vacc. 1 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Irritability Post-vacc. 2 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Irritability Post-vacc. 3 (n=2,1,0,0,0,0)	0	0	99999	99999	99999	99999
Irritability Post-vacc. 4 (n=2,1,0,0,0,0)	1	0	99999	99999	99999	99999
Headache Post-any Vacc. (n=110,55,26,14,129,65)	20	10	5	3	31	11
Headache Post-vacc. 1 (n=110,55,26,14,129,65)	11	7	4	1	19	7
Headache Post-vacc. 2 (n=109,55,23,14,129,65)	8	3	3	2	10	2
Headache Post-vacc. 3 (n=110,55,21,12,129,65)	7	4	0	2	10	3
Headache Post-vacc. 4 (n=110,55,0,0,127,64)	6	1	99999	99999	8	2
Malaise Post-any Vacc. (n=110,55,26,14,129,65)	18	9	6	5	39	13
Malaise Post-vacc. 1 (n=110,55,26,14,129,65)	13	6	5	4	26	5
Malaise Post-vacc. 2 (n=108,55,23,14,128,65)	8	4	2	1	17	3
Malaise Post-vacc. 3 (n=109,55,21,12,129,65)	3	2	1	1	17	5
Malaise Post-vacc. 4 (n=110,55,0,0,127,64)	6	2	99999	99999	12	5
Myalgia Post-any Vacc. (n=110,55,26,14,129,65)	26	10	11	8	61	25
Myalgia Post-vacc. 1 (n=110,55,26,14,129,65)	13	6	11	6	44	21
Myalgia Post-vacc. 2 (n=109,55,23,14,129,65)	16	6	3	0	25	11
Myalgia Post-vacc. 3 (n=108,55,21,12,129,65)	5	4	1	2	21	8
Myalgia Post-vacc. 4 (n=110,55,0,0,127,64)	7	4	99999	99999	20	6

No statistical analyses for this end point

Secondary: Number of Subjects With Unsolicited AEs

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End point title

Number of Subjects With Unsolicited AEs

End point description

An AE was defined as any untoward medical occurrence in a subject who received study vaccine and does not necessary had to have a causal relationship with treatment. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination. Analysis was performed on SafAS. Here, 'n' = subjects with available data for each specified category. Here, "99999" is used as a space filler and denotes that no subjects were available for analysis for the specified category at each specified timepoint. Reported AEs were presented for each arm as pre-specified in the protocol.

End point type

Secondary

End point timeframe

Within 28 days post any and each vaccination (Vaccination 1 [Day 0], 2 [Day 3], 3 [Day 7] and 4 [Day 28])

End point values	Group 1: VRVg-2	Group 2: Verorab®	Group 3: VRVg-2 + ERIG	Group 4: Verorab® + ERIG	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Number of subjects analysed	112	56	26	14	129	65
Units: subjects
Post-any Vacc. (n=112,56,26,14,129,65)	22	12	26	12	4	2
Post Vacc. 1 (n=112,56,26,14,129,65)	1	1	25	12	3	0
Post Vacc. 2 (n=112,56,23,14,129,65)	4	0	3	1	0	1
Post Vacc. 3 (n=112,56,21,12,129,65)	12	5	5	2	0	0
Post Vacc. 4 (n=112,56,0,0,127,64)	7	7	99999	99999	1	1

No statistical analyses for this end point

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

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End point title

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

End point description

An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required initial or prolonged inpatient hospitalisation, resulted in persistent or significant disability/incapacity, congenital anomaly/birth defect or was 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. Relatedness to study vaccine was based on Investigator's discretion. Analysis was performed on SafAS. Reported AEs were presented for each arm as pre-specified in the protocol.

End point type

Secondary

End point timeframe

From Day 0 up to 6 months after last vaccination (i.e., up to Month 7)

End point values	Group 1: VRVg-2	Group 2: Verorab®	Group 3: VRVg-2 + ERIG	Group 4: Verorab® + ERIG	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Number of subjects analysed	112	56	26	14	129	65
Units: subjects
SAEs	0	0	1	2	5	3
AESIs	0	0	0	0	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Unsolicited AEs were collected from Day 0 up to 28 days post any and each vaccination. SR data were collected up to 7 days post any and each vaccination. SAE data were collected from Day 0 up to 6 months post last vaccination (i.e., up to Month 7)

Adverse event reporting additional description

SR: expected AR observed & reported under conditions (nature and onset) prelisted (i.e., solicited) in protocol & CRB & considered as related vaccination. Unsolicited AE: AE that did not fulfill conditions prelisted (i.e., solicited) in CRB in terms of diagnosis & onset window post-vaccination. SafAS. In AE section, SR fever is reported as pyrexia.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.0

Reporting group title

Group 1: VRVg-2

Reporting group description

Pediatric subjects aged 1 year to < 18 years received 8 injections (1 vaccination on each arm) of 0.5 mL of VRVg-2 intradermally on Days 0, 3, 7 and 28.

Reporting group title

Group 2: Verorab

Reporting group description

Reporting group title

Group 3: VRVg-2 + ERIG

Reporting group description

Adult subjects aged 18 year and above received 6 injections (1 vaccination on each arm) of 0.5 mL VRVg-2 intradermally on Days 0, 3 and 7 along with ERIG IM injection at Day 0.

Reporting group title

Group 4: Verorab + ERIG

Reporting group description

Adult subjects aged 18 year and above received 6 injections (1 vaccination on each arm) of 0.5 mL Verorab® intradermally on Days 0, 3 and 7 along with ERIG IM injection at Day 0.

Reporting group title

Group 5: VRVg-2 + HRIG

Reporting group description

Adult subjects aged 18 year and above received 8 injections (1 vaccination on each arm) of 0.5 mL VRVg-2 intradermally on Days 0, 3, 7, and 28 along with HRIG IM injection at Day 0.

Reporting group title

Group 6: Verorab + HRIG

Reporting group description

Adult subjects aged 18 year and above received 8 injections (1 vaccination on each arm) of 0.5 mL Verorab® intradermally on Days 0, 3, 7, and 28 along with HRIG IM injection at Day 0.

Serious adverse events	Group 1: VRVg-2	Group 2: Verorab	Group 3: VRVg-2 + ERIG	Group 4: Verorab + ERIG	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 112 (0.00%)	0 / 56 (0.00%)	1 / 26 (3.85%)	2 / 14 (14.29%)	5 / 129 (3.88%)	3 / 65 (4.62%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events
Injury, poisoning and procedural complications
Limb Traumatic Amputation
subjects affected / exposed	0 / 112 (0.00%)	0 / 56 (0.00%)	0 / 26 (0.00%)	0 / 14 (0.00%)	1 / 129 (0.78%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Surgical and medical procedures
Mammoplasty
subjects affected / exposed	0 / 112 (0.00%)	0 / 56 (0.00%)	0 / 26 (0.00%)	0 / 14 (0.00%)	0 / 129 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 112 (0.00%)	0 / 56 (0.00%)	1 / 26 (3.85%)	0 / 14 (0.00%)	0 / 129 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Lower Gastrointestinal Haemorrhage
subjects affected / exposed	0 / 112 (0.00%)	0 / 56 (0.00%)	0 / 26 (0.00%)	0 / 14 (0.00%)	0 / 129 (0.00%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Angioedema
subjects affected / exposed	0 / 112 (0.00%)	0 / 56 (0.00%)	0 / 26 (0.00%)	1 / 14 (7.14%)	0 / 129 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypersensitivity Vasculitis
subjects affected / exposed	0 / 112 (0.00%)	0 / 56 (0.00%)	0 / 26 (0.00%)	1 / 14 (7.14%)	0 / 129 (0.00%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis Perforated
subjects affected / exposed	0 / 112 (0.00%)	0 / 56 (0.00%)	0 / 26 (0.00%)	0 / 14 (0.00%)	1 / 129 (0.78%)	0 / 65 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Covid-19
subjects affected / exposed	0 / 112 (0.00%)	0 / 56 (0.00%)	0 / 26 (0.00%)	0 / 14 (0.00%)	3 / 129 (2.33%)	1 / 65 (1.54%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	0 / 1
deaths causally related to treatment / all	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	Group 1: VRVg-2	Group 2: Verorab	Group 3: VRVg-2 + ERIG	Group 4: Verorab + ERIG	Group 5: VRVg-2 + HRIG	Group 6: Verorab + HRIG
Total subjects affected by non serious adverse events
subjects affected / exposed	85 / 112 (75.89%)	42 / 56 (75.00%)	26 / 26 (100.00%)	14 / 14 (100.00%)	80 / 129 (62.02%)	38 / 65 (58.46%)
Nervous system disorders
Headache
Additional description: Headache events that occurred after 7 days post-vaccination were considered as unsolicited AE.
subjects affected / exposed	20 / 112 (17.86%)	11 / 56 (19.64%)	5 / 26 (19.23%)	3 / 14 (21.43%)	31 / 129 (24.03%)	11 / 65 (16.92%)
occurrences all number	34	16	7	5	47	14
General disorders and administration site conditions
Application Site Pain
subjects affected / exposed	0 / 112 (0.00%)	0 / 56 (0.00%)	7 / 26 (26.92%)	2 / 14 (14.29%)	0 / 129 (0.00%)	0 / 65 (0.00%)
occurrences all number	0	0	7	2	0	0
Injection Site Erythema
subjects affected / exposed	40 / 112 (35.71%)	15 / 56 (26.79%)	0 / 26 (0.00%)	0 / 14 (0.00%)	0 / 129 (0.00%)	2 / 65 (3.08%)
occurrences all number	168	76	0	0	0	2
Injection Site Pain
subjects affected / exposed	44 / 112 (39.29%)	23 / 56 (41.07%)	14 / 26 (53.85%)	5 / 14 (35.71%)	57 / 129 (44.19%)	30 / 65 (46.15%)
occurrences all number	177	81	37	11	200	102
Injection Site Swelling
subjects affected / exposed	53 / 112 (47.32%)	27 / 56 (48.21%)	0 / 26 (0.00%)	0 / 14 (0.00%)	0 / 129 (0.00%)	0 / 65 (0.00%)
occurrences all number	243	116	0	0	0	0
Malaise
subjects affected / exposed	18 / 112 (16.07%)	9 / 56 (16.07%)	6 / 26 (23.08%)	5 / 14 (35.71%)	39 / 129 (30.23%)	13 / 65 (20.00%)
occurrences all number	30	14	8	6	72	18
Pyrexia
Additional description: Pyrexia/Fever events that occurred after 7 days post-vaccination were considered as unsolicited AE.
subjects affected / exposed	1 / 112 (0.89%)	1 / 56 (1.79%)	2 / 26 (7.69%)	0 / 14 (0.00%)	2 / 129 (1.55%)	2 / 65 (3.08%)
occurrences all number	1	1	2	0	2	2
Skin and subcutaneous tissue disorders
Urticaria
subjects affected / exposed	1 / 112 (0.89%)	0 / 56 (0.00%)	7 / 26 (26.92%)	2 / 14 (14.29%)	0 / 129 (0.00%)	0 / 65 (0.00%)
occurrences all number	1	0	7	2	0	0
Musculoskeletal and connective tissue disorders
Myalgia
Additional description: Myalgia events that occurred after 7 days post-vaccination were considered as unsolicited AE.
subjects affected / exposed	26 / 112 (23.21%)	10 / 56 (17.86%)	19 / 26 (73.08%)	12 / 14 (85.71%)	61 / 129 (47.29%)	25 / 65 (38.46%)
occurrences all number	41	20	33	18	113	46
Infections and infestations
Upper Respiratory Tract Infection
subjects affected / exposed	10 / 112 (8.93%)	7 / 56 (12.50%)	0 / 26 (0.00%)	0 / 14 (0.00%)	0 / 129 (0.00%)	0 / 65 (0.00%)
occurrences all number	10	7	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

20 Nov 2019

Protocol amended for update of Principal investigator.

22 Nov 2021

Following changes were made: Deleted virus complete or incomplete neutralisation endpoint at 1/5 dilution. Wording changed to clarify new sample size calculated. Adult study arm receiving vaccines + ERIG was temporary halt by Sponsor for safety reasons after enrolling 40 subjects, following receipt of cluster of 3 SAEs of hypersensitivity assessed as related to both ERIG and study vaccine by investigator, & assessed as unrelated to study vaccine but related to ERIG by sponsor. Therefore, ERIG administration on Day (D) 0 in adult subjects (Groups 3 and 4) was discontinued and HRIG was then co-administrated on D0 in Groups 5 and 6. Wording changed to clarify: ERIG administration was applied for Groups 3 & 4 & HRIG administration was applied for Groups 5 & 6. Primary immunogenicity objective modified. Additional immunogenicity secondary objective added: Included immunogenicity data analysis for adult subjects in Groups 3 & 4 to evaluate immune response induced by VRVg-2 & Verorab vaccine at D14. Secondary immunogenicity objective on D90 was applied only for adult subjects in Groups 5 and 6 since no immunogenicity data was available at D90 for Groups 3 & 4. Informed that safety profile was described for all groups. Wording changed to clarify the statistical analysis for the new sample size calculated. Wording changed to clarify that ERIG administration was applied only for Groups 3 & 4 & to provide ERIG batch number used until study halt. Deleted "optional, based on Investigator’s judgement” since TRC Society ERIG recommended doing positive skin test prior administration. However, it was agreed with the investigators to do the test in all subjects as additional precautionary safety measure. Missing Diary Cards numbers added. Wording changed since the assessment of immediate unsolicited systemic events was recorded in V01, V02, V03 and V05 only. Footnote removed to clarify event reporting at D0. Injection site reaction and systemic AE/AR recorded daily (from V01 to V07).

24 Jun 2022

Following changes were made: Modified GSO representative contact details. Modified justification of study design to clarify that after the discontinuation of ERIG, the 40 subjects were withdrawn and excluded from the PPAS for D42 because unable to complete the 4-dose vaccination schedule, and part of the 40 subjects were also excluded from the PPAS for D14 because unable to complete the first 3 doses of the vaccination schedule. Paragraph added to explain the rationale for developing amendment 3. Re-inserted Amendment 1 to provide history of protocol amendments. Per-protocol analysis set for D42 - paragraph modified to clarify PPAS for D42 definition and notably to remove blood sample 2 at D14 from the list of exclusion criteria.

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

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of Subjects With Rabies Virus Neutralising Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 International Units per Mililitres (IU/mL)

Primary: Percentage of Subjects With Rabies Virus Neutralising Antibody (RVNA) Titer Greater Than or Equal to (>=) 0.5 International Units per Mililitres (IU/mL)

Primary: Percentage of Subjects With RVNA Titer >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

Primary: Percentage of Subjects With RVNA Titer >=0.2 IU/mL (Lower Limit of Quantification [LLOQ])

Primary: Geometric Mean Titer Ratios (GMTRs) of Individual RVNA Titers

Primary: Geometric Mean Titer Ratios (GMTRs) of Individual RVNA Titers

Secondary: Percentage of Subjects With RVNA Titer >= 0.5 IU/mL: Group 3 and Group 4

Secondary: Percentage of Subjects With RVNA Titer >= 0.5 IU/mL: Group 3 and Group 4

Secondary: Percentage of Subjects With RVNA Titer >= 0.2 IU/mL (LLOQ): Group 3 and Group 4

Secondary: Percentage of Subjects With RVNA Titer >= 0.2 IU/mL (LLOQ): Group 3 and Group 4

Secondary: GMTRs of Individual RVNA Titers: Group 3 and Group 4

Secondary: GMTRs of Individual RVNA Titers: Group 3 and Group 4

Secondary: Percentage of Subjects With RVNA Titer >= 0.5 IU/mL: Groups 1, 2, 5 and 6

Secondary: Percentage of Subjects With RVNA Titer >= 0.5 IU/mL: Groups 1, 2, 5 and 6

Secondary: Percentage of Subjects With RVNA Titer >= 0.2 IU/mL (LLOQ): Groups 1, 2, 5 and 6

Secondary: Percentage of Subjects With RVNA Titer >= 0.2 IU/mL (LLOQ): Groups 1, 2, 5 and 6

Secondary: GMTRs of Individual RVNA Titers: Groups 1, 2, 5 and 6

Secondary: GMTRs of Individual RVNA Titers: Groups 1, 2, 5 and 6

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

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

Secondary: Number of Subjects With Solicited Injection Site Reactions

Secondary: Number of Subjects With Solicited Injection Site Reactions

Secondary: Number of Subjects With Solicited Systemic Reactions

Secondary: Number of Subjects With Solicited Systemic Reactions

Secondary: Number of Subjects With Unsolicited AEs

Secondary: Number of Subjects With Unsolicited AEs

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

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

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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