Trial Outcomes & Findings for A Phase 3 Clinical Trial to Evaluate Long-term Immunogenicity and Boostability of Purified Chick-Embryo Cell Rabies Vaccine in Adults Following Primary Series of Pre/Exposure Prophylaxis. (NCT NCT02545517)

NCT ID: NCT02545517

Last Updated: 2024-07-18

Results Overview

A SAE is defined as any untoward medical occurrence that at any dose results in one or more of the following: death, is life-threatening, required/prolonged hospitalization, persistent or significant disability/incapacity, congenital anomaly/or birth defect, an important and significant medical event that may not be immediately life threatening or resulting in death or hospitalization but, based upon appropriate medical judgment, may jeopardize the participants or may require intervention to prevent one of the other outcomes listed. Safety is assessed as the number of participants reporting SAEs after a booster dose of PCEC rabies vaccine administered in this extension study, if RNVA concentrations were \<0.5 IU/mL, following a primary series of accelerated or conventional rabies pre-exposure (PrEP) intramuscular (IM) regimen in the parent study.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 459 participants
• Primary outcome timeframe: From booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination)
• Results posted on: 2024-07-18

Participant Flow

Up to 459 participants, who successfully completed rabies pre-exposure prophylaxis (PrEP) regimens in parent study (V49_23) (NCT01662440, EudraCT ID- 2011-005173-23) and did not have protocol deviations which could impact the immunogenicity response (e.g., wrong vaccination) were enrolled in this extension study.

As prespecified in protocol, Visit 1 in the extension study corresponds to Year 3, i.e. approximately 3 years after completion of rabies primary series in the parent study. Subsequent visits (2,3,4,5,6,7 and 8) occurred at yearly intervals applied after completion of parent study (Year 4, 5, 6, 7, 8, 9 and 10).

Participant milestones

Measure	Conv-R/JE Group Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Overall Study STARTED	126	157	176
Overall Study COMPLETED	98	123	135
Overall Study NOT COMPLETED	28	34	41

Reasons for withdrawal

Measure	Conv-R/JE Group Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Overall Study Death	2	2	1
Overall Study Lost to Follow-up	14	13	17
Overall Study Protocol Violation	0	1	1
Overall Study Withdrawal by Subject	5	8	9
Overall Study Administrative reason	5	6	10
Overall Study Other	2	4	3

Baseline Characteristics

A Phase 3 Clinical Trial to Evaluate Long-term Immunogenicity and Boostability of Purified Chick-Embryo Cell Rabies Vaccine in Adults Following Primary Series of Pre/Exposure Prophylaxis.

Baseline characteristics by cohort

Measure	Conv-R/JE Group n=126 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=157 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=176 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Total n=459 Participants Total of all reporting groups
Age, Continuous	37.9 YEARS STANDARD_DEVIATION 13.2 • n=5 Participants	38.7 YEARS STANDARD_DEVIATION 13.0 • n=7 Participants	36.6 YEARS STANDARD_DEVIATION 12.8 • n=5 Participants	37.7 YEARS STANDARD_DEVIATION 13.0 • n=4 Participants
Sex: Female, Male Female	61 Participants n=5 Participants	94 Participants n=7 Participants	101 Participants n=5 Participants	256 Participants n=4 Participants
Sex: Female, Male Male	65 Participants n=5 Participants	63 Participants n=7 Participants	75 Participants n=5 Participants	203 Participants n=4 Participants
Race/Ethnicity, Customized ASIAN	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized OTHER UNSPECIFIED	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	3 Participants n=4 Participants
Race/Ethnicity, Customized WHITE	125 Participants n=5 Participants	154 Participants n=7 Participants	173 Participants n=5 Participants	452 Participants n=4 Participants

PRIMARY outcome

Timeframe: From booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination)

Population: The analysis was performed on the Safety Set which included all enrolled participants who received a booster dose and reported safety data.

A SAE is defined as any untoward medical occurrence that at any dose results in one or more of the following: death, is life-threatening, required/prolonged hospitalization, persistent or significant disability/incapacity, congenital anomaly/or birth defect, an important and significant medical event that may not be immediately life threatening or resulting in death or hospitalization but, based upon appropriate medical judgment, may jeopardize the participants or may require intervention to prevent one of the other outcomes listed.

Safety is assessed as the number of participants reporting SAEs after a booster dose of PCEC rabies vaccine administered in this extension study, if RNVA concentrations were <0.5 IU/mL, following a primary series of accelerated or conventional rabies pre-exposure (PrEP) intramuscular (IM) regimen in the parent study.

Outcome measures

Measure	Conv-R/JE Group n=44 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=47 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=53 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Number of Participants Reporting Serious Adverse Events (SAEs) After a Booster Dose of Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine	2 Participants	0 Participants	3 Participants

PRIMARY outcome

Timeframe: Day 366 to Year 3 (after primary series of vaccination)

Population: The analysis was performed on the Full Analysis Set-2 (FAS-2): long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=96 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=98 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=133 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Number of Participants Who Had Their Rabies Virus Neutralizing Antibody (RNVA) Concentrations Drop Below 0.5 International Units (IU) Per Milliliter (mL) Between Day 366 and Year 3	1 Participants	1 Participants	2 Participants

PRIMARY outcome

Timeframe: Year 3 to Year 4 (after primary series of vaccination)

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=93 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=92 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=133 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 3 and Year 4	5 Participants	5 Participants	7 Participants

PRIMARY outcome

Timeframe: Year 4 to Year 5 (after primary series of vaccination)

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=85 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=84 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=117 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 4 and Year 5	7 Participants	0 Participants	4 Participants

PRIMARY outcome

Timeframe: Year 5 to Year 6 (after primary series of vaccination)

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=72 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=83 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=112 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 5 and Year 6	3 Participants	2 Participants	10 Participants

PRIMARY outcome

Timeframe: Year 6 to Year 7 (after primary series of vaccination)

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=67 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=78 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=101 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 6 and Year 7	0 Participants	2 Participants	0 Participants

PRIMARY outcome

Timeframe: Year 7 to Year 8 (after primary series of vaccination)

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=67 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=74 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=97 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 7 and Year 8	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Year 8 to Year 9 (after primary series of vaccination)

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=66 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=72 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=93 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 8 and Year 9	1 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: Year 9 to Year 10 (after primary series of vaccination)

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=61 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=69 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=85 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 9 and Year 10	2 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: At Day 7 after booster dose

Population: Analysis was performed on the Full Analysis Set-1 (FAS-1): booster immunogenicity analysis, which included all eligible participants from the V49\_23 study enrolled in this extension study, whom received booster dose (booster dose was administered only when participants reached RVNA concentrations \<0.5 IU/mL) and provided immunogenicity data for the specific analysis at the specific timepoint.

RVNA antibody concentrations were measured in terms of Geometric Mean Concentrations (GMCs) and expressed in IU/mL. The booster dose was administered in this Extension study (conducted from Year 3 to Year 9 after the primary schedule study) only when participants had RVNA concentrations <0.5 IU/mL at the yearly immunogenicity check (i.e., at "Scheduled Clinic Visit"). Booster dose administration occurred at an approximate timepoint between 6 and 9 months from the previous "Scheduled Clinic Visit" during the Years 3 to 9.

Outcome measures

Measure	Conv-R/JE Group n=43 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=46 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=52 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
RVNA Antibody Concentrations 7 Days After the Booster Dose	4.2 IU/mL Interval 2.8 to 6.4	4.2 IU/mL Interval 2.8 to 6.2	4.4 IU/mL Interval 3.0 to 6.4

PRIMARY outcome

Timeframe: Day 7 after booster dose compared to baseline (7 days before booster dose)

Population: Analysis was performed on the FAS-1: booster immunogenicity analysis, which included all eligible participants from the V49\_23 study enrolled in this extension study, whom received booster dose (booster dose was administered only when participants reached RVNA concentrations \<0.5 IU/mL) and provided immunogenicity data for the specific analysis at the specific timepoint.

GMR was calculated as ratio of post booster dose RVNA GMCs (7-day post booster dose) to the baseline RVNA GMCs (7 days before booster dose). The booster dose was administered in this Extension study (conducted from Year 3 to Year 9 after the primary schedule study) only when participants had RVNA concentrations <0.5 IU/mL at the yearly immunogenicity check (i.e., at "Scheduled Clinic Visit"). Booster dose administration occurred at an approximate timepoint between 6 and 9 months from the previous "Scheduled Clinic Visit" during the Years 3 to 9.

Outcome measures

Measure	Conv-R/JE Group n=43 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=46 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=52 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
RVNA Geometric Mean Ratios (GMRs) 7 Days After the Booster Dose Versus Antibody Concentrations Before the Booster Dose	23.6 Ratio Interval 16.1 to 34.4	23.4 Ratio Interval 16.2 to 33.8	19.3 Ratio Interval 13.7 to 27.3

PRIMARY outcome

Timeframe: At Day 7 after booster dose

Population: Analysis was performed on the FAS-1: booster immunogenicity analysis, which included all eligible participants from the V49\_23 study enrolled in this extension study, whom received booster dose (booster dose was administered only when participants reached RVNA concentrations \<0.5 IU/mL) and provided immunogenicity data for the specific analysis at the specific timepoint.

The booster dose was administered in this Extension study (conducted from Year 3 to Year 9 after the primary schedule study) only when participants had RVNA concentrations <0.5 IU/mL at the yearly immunogenicity check (i.e., at "Scheduled Clinic Visit"). Booster dose administration occurred at an approximate timepoint between 6 and 9 months from the previous "Scheduled Clinic Visit" during the Years 3 to 9.

Outcome measures

Measure	Conv-R/JE Group n=43 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=46 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=52 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Percentage of Participants With RVNA Concentrations Greater Than or Equal to (>=) 0.5 IU/mL, 7 Days After Booster Dose	95.3 Percentage of participants Interval 84.2 to 99.4	89.1 Percentage of participants Interval 76.4 to 96.4	98.1 Percentage of participants Interval 89.7 to 100.0

PRIMARY outcome

Timeframe: At Year 3 after primary series of vaccine administration

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=125 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=151 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=172 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 3	81.6 Percentage of participants Interval 73.7 to 88.0	78.8 Percentage of participants Interval 71.4 to 85.0	84.9 Percentage of participants Interval 78.6 to 89.9

PRIMARY outcome

Timeframe: At Year 4 after primary series of vaccine administration

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=121 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=144 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=166 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 4	74.4 Percentage of participants Interval 65.6 to 81.9	70.8 Percentage of participants Interval 62.7 to 78.1	76.5 Percentage of participants Interval 69.3 to 82.7

PRIMARY outcome

Timeframe: At Year 5 after primary series of vaccine administration

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=118 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=139 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=160 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 5	66.1 Percentage of participants Interval 56.8 to 74.6	69.1 Percentage of participants Interval 60.7 to 76.6	73.1 Percentage of participants Interval 65.6 to 79.8

PRIMARY outcome

Timeframe: At Year 6 after primary series of vaccine administration

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=110 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=139 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=158 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 6	60.9 Percentage of participants Interval 51.1 to 70.1	66.2 Percentage of participants Interval 57.7 to 74.0	66.5 Percentage of participants Interval 58.5 to 73.8

PRIMARY outcome

Timeframe: At Year 7 after primary series of vaccine administration

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=108 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=135 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=156 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 7	60.2 Percentage of participants Interval 50.3 to 69.5	64.4 Percentage of participants Interval 55.8 to 72.5	67.3 Percentage of participants Interval 59.3 to 74.6

PRIMARY outcome

Timeframe: At Year 8 after primary series of vaccine administration

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=107 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=131 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=144 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 8	59.8 Percentage of participants Interval 49.9 to 69.2	64.1 Percentage of participants Interval 55.3 to 72.3	64.6 Percentage of participants Interval 56.2 to 72.4

PRIMARY outcome

Timeframe: At Year 9 after primary series of vaccine administration

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=108 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=132 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=150 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 9	59.3 Percentage of participants Interval 49.4 to 68.6	63.6 Percentage of participants Interval 54.8 to 71.8	64.0 Percentage of participants Interval 55.8 to 71.7

PRIMARY outcome

Timeframe: At Year 10 after primary series of vaccine administration

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoint.

Outcome measures

Measure	Conv-R/JE Group n=105 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=130 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=142 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 10	56.2 Percentage of participants Interval 46.2 to 65.9	62.3 Percentage of participants Interval 53.4 to 70.7	62.7 Percentage of participants Interval 54.2 to 70.6

SECONDARY outcome

Timeframe: At Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and Year 10 after primary series of vaccine administration

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoints.

Antibody concentrations were measured in terms of GMCs and expressed in IU/mL.

Outcome measures

Measure	Conv-R/JE Group n=125 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=151 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=172 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Rabies Virus Neutralizing Antibody Concentrations Year 3	1.21 IU/mL Interval 0.88 to 1.65	1.16 IU/mL Interval 0.87 to 1.55	1.3 IU/mL Interval 0.99 to 1.7
Rabies Virus Neutralizing Antibody Concentrations Year 4	0.69 IU/mL Interval 0.5 to 0.94	0.73 IU/mL Interval 0.55 to 0.97	0.82 IU/mL Interval 0.63 to 1.07
Rabies Virus Neutralizing Antibody Concentrations Year 5	0.66 IU/mL Interval 0.48 to 0.9	0.7 IU/mL Interval 0.53 to 0.94	0.74 IU/mL Interval 0.56 to 0.96
Rabies Virus Neutralizing Antibody Concentrations Year 6	0.5 IU/mL Interval 0.37 to 0.69	0.6 IU/mL Interval 0.45 to 0.8	0.58 IU/mL Interval 0.44 to 0.76
Rabies Virus Neutralizing Antibody Concentrations Year 7	0.49 IU/mL Interval 0.36 to 0.67	0.6 IU/mL Interval 0.45 to 0.79	0.61 IU/mL Interval 0.47 to 0.8
Rabies Virus Neutralizing Antibody Concentrations Year 8	0.56 IU/mL Interval 0.41 to 0.77	0.76 IU/mL Interval 0.57 to 1.01	0.68 IU/mL Interval 0.52 to 0.89
Rabies Virus Neutralizing Antibody Concentrations Year 9	0.53 IU/mL Interval 0.39 to 0.73	0.7 IU/mL Interval 0.53 to 0.94	0.62 IU/mL Interval 0.47 to 0.81
Rabies Virus Neutralizing Antibody Concentrations Year 10	0.59 IU/mL Interval 0.43 to 0.81	0.72 IU/mL Interval 0.54 to 0.96	0.68 IU/mL Interval 0.52 to 0.89

SECONDARY outcome

Timeframe: At Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and Year 10 after primary series of vaccine administration

Population: The analysis was performed on the FAS-2: long term immunogenicity analysis which included all eligible participants from the V49\_23 study enrolled in this extension study and provided immunogenicity data for the specific analysis at the specific timepoints.

As specified in the statistical analysis plan, a graphical presentation of the Reverse Cumulative Distribution Plots for participants with RVNA concentrations >=0.5 IU/mL was analyzed for this outcome measure. Due to system constrains, only the reverse cumulative percentage values were reported, to depict the Reverse Cumulative Distribution Plots.

Outcome measures

Measure	Conv-R/JE Group n=125 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=151 Participants Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=172 Participants Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL Year 6	54 Cumulative percentage of participants	57 Cumulative percentage of participants	56 Cumulative percentage of participants
Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL Year 7	43 Cumulative percentage of participants	45 Cumulative percentage of participants	44 Cumulative percentage of participants
Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL Year 9	21 Cumulative percentage of participants	22 Cumulative percentage of participants	21 Cumulative percentage of participants
Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL Year 3	100 Cumulative percentage of participants	100 Cumulative percentage of participants	100 Cumulative percentage of participants
Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL Year 4	83 Cumulative percentage of participants	84 Cumulative percentage of participants	83 Cumulative percentage of participants
Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL Year 5	67 Cumulative percentage of participants	70 Cumulative percentage of participants	69 Cumulative percentage of participants
Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL Year 8	32 Cumulative percentage of participants	33 Cumulative percentage of participants	32 Cumulative percentage of participants
Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL Year 10	10 Cumulative percentage of participants	11 Cumulative percentage of participants	10 Cumulative percentage of participants

Adverse Events

Conv-R/JE Group

Serious events: 2 serious events

Other events: 0 other events

Deaths: 2 deaths

Acc-R/JE Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 2 deaths

Conv-R Group

Serious events: 3 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Measure	Conv-R/JE Group n=44 participants at risk Participants who completed the Rabies PrEP regimen on days 1, 8 and 29, and Japanese Encephalitis (JE) primary series regimen on days 1 and 29 in the parent study (V49\_23) and who received at least one booster dose of purified chick embryo cell culture (PCEC) rabies vaccine in this extension study, if Rabies Virus Neutralizing Antibody (RNVA) concentrations were less than (\<)0.5 IU/mL at scheduled visits.	Acc-R/JE Group n=47 participants at risk Participants who completed the Rabies PrEP regimen on days 1, 4 and 8 and JE primary series regimen on days 1 and 8 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.	Conv-R Group n=53 participants at risk Participants who completed the Rabies PrEP regimen on days 1, 8 and 29 in the parent study (V49\_23) and who received at least one booster dose of PCEC rabies vaccine in this extension study, if RNVA concentrations were \<0.5 IU/mL at scheduled visits.
Gastrointestinal disorders Diarrhoea	0.00% 0/44 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.	0.00% 0/47 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.	1.9% 1/53 • Number of events 1 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Leiomyoma	0.00% 0/44 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.	0.00% 0/47 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.	1.9% 1/53 • Number of events 1 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.
Psychiatric disorders Completed suicide	0.00% 0/44 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.	0.00% 0/47 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.	1.9% 1/53 • Number of events 1 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	2.3% 1/44 • Number of events 1 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.	0.00% 0/47 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.	0.00% 0/53 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.
Vascular disorders Deep vein thrombosis	2.3% 1/44 • Number of events 1 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.	0.00% 0/47 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.	0.00% 0/53 • All Cause Mortality: from Year 3 (3 years after primary series of vaccination) up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs: from booster vaccination [6 to 9 months after Year 3 (3 years after primary series of vaccination)] up until completion of the safety follow-up period (10 years after primary series of vaccination) SAEs were collected only from participants who received booster dose. Five deaths were recorded during this extension study but only one of them was reported as SAE as this was the only one that occurred in a participant who received a booster dose. Solicited and non-serious unsolicited AEs were not collected in this study.

Other adverse events

Adverse event data not reported

Additional Information

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GlaxoSmithKline

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Email: GSKClinicalSupportHD@gsk.com

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