Virus Diseases, Rabies
Conditions
Keywords
Rabies disease, Pre-exposure (PrEP) or post exposure prophylaxis (PEP), Long-term Immunogenicity
Brief summary
The aim of this study is to evaluate the long-term (up to approx.10 years) persistence and to assess the boostability of immune responses in participants who received a primary series of accelerated or conventional rabies PrEP IM regimen. This product has been transferred to BN. GSK Clinical Study Register is no longer maintained for this study. The most up to date information is available on www.clinicaltrials.gov.
Interventions
BIOLOGICALRabipur
Participants in all the groups received Rabipur vaccine booster dose, administered intramuscularly in the deltoid region of the non-dominant arm.
PROCEDUREBlood sampling
Blood samples were drawn from all participants at Day 1 and then at subsequent year intervals from extension study Day 1 onwards.
1 booster dose of 1.0 mL of Purified Chick-Embryo Cell Rabies Vaccine intramuscular (IM).
Sponsors
GlaxoSmithKline
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
Inclusion criteria
* All individuals who were randomized to a Rabies primary series vaccination for pre-exposure prophylaxis (PrEP), received the full PrEP regimen and completed the parent trial following study protocol.
Exclusion criteria
* Completed the parent study without receiving the full 3 rabies vaccine doses following the assigned pre-exposure prophylaxis regimen. * History of exposure to suspected or confirmed rabid animal. * Receipt of rabies immunoglobulins, rabies post exposure prophylaxis following completion of the parent study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 10 | At Year 10 after primary series of vaccine administration | — |
| Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 8 | At Year 8 after primary series of vaccine administration | — |
| Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 9 | At Year 9 after primary series of vaccine administration | — |
| Number of Participants Reporting Serious Adverse Events (SAEs) After a Booster Dose of Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine | 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) | 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. |
| 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 | Day 366 to Year 3 (after primary series of vaccination) | — |
| Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 3 and Year 4 | Year 3 to Year 4 (after primary series of vaccination) | — |
| Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 4 and Year 5 | Year 4 to Year 5 (after primary series of vaccination) | — |
| Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 5 and Year 6 | Year 5 to Year 6 (after primary series of vaccination) | — |
| Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 6 and Year 7 | Year 6 to Year 7 (after primary series of vaccination) | — |
| Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 7 and Year 8 | Year 7 to Year 8 (after primary series of vaccination) | — |
| Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 8 and Year 9 | Year 8 to Year 9 (after primary series of vaccination) | — |
| Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 9 and Year 10 | Year 9 to Year 10 (after primary series of vaccination) | — |
| RVNA Antibody Concentrations 7 Days After the Booster Dose | At Day 7 after booster dose | 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. |
| RVNA Geometric Mean Ratios (GMRs) 7 Days After the Booster Dose Versus Antibody Concentrations Before the Booster Dose | Day 7 after booster dose compared to baseline (7 days before booster dose) | 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. |
| Percentage of Participants With RVNA Concentrations Greater Than or Equal to (>=) 0.5 IU/mL, 7 Days After Booster Dose | At Day 7 after 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. |
| Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 3 | At Year 3 after primary series of vaccine administration | — |
| Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 4 | At Year 4 after primary series of vaccine administration | — |
| Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 5 | At Year 5 after primary series of vaccine administration | — |
| Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 6 | At Year 6 after primary series of vaccine administration | — |
| Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 7 | At Year 7 after primary series of vaccine administration | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | At Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and Year 10 after primary series of vaccine administration | 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. |
| Rabies Virus Neutralizing Antibody Concentrations | At Year 3, Year 4, Year 5, Year 6, Year 7, Year 8, Year 9 and Year 10 after primary series of vaccine administration | Antibody concentrations were measured in terms of GMCs and expressed in IU/mL. |
Countries
Austria, Germany, Switzerland
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 126 |
| 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. | 157 |
| 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. | 176 |
| Total | 459 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Administrative reason | 5 | 6 | 10 |
| Overall Study | Death | 2 | 2 | 1 |
| Overall Study | Lost to Follow-up | 14 | 13 | 17 |
| Overall Study | Other | 2 | 4 | 3 |
| Overall Study | Protocol Violation | 0 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 5 | 8 | 9 |
Baseline characteristics
| Characteristic | Conv-R/JE Group | Acc-R/JE Group | Conv-R Group | Total |
|---|---|---|---|---|
| Age, Continuous | 37.9 YEARS STANDARD_DEVIATION 13.2 | 38.7 YEARS STANDARD_DEVIATION 13 | 36.6 YEARS STANDARD_DEVIATION 12.8 | 37.7 YEARS STANDARD_DEVIATION 13 |
| Race/Ethnicity, Customized ASIAN | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized OTHER UNSPECIFIED | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized WHITE | 125 Participants | 154 Participants | 173 Participants | 452 Participants |
| Sex: Female, Male Female | 61 Participants | 94 Participants | 101 Participants | 256 Participants |
| Sex: Female, Male Male | 65 Participants | 63 Participants | 75 Participants | 203 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 126 | 2 / 157 | 1 / 176 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 2 / 44 | 0 / 47 | 3 / 53 |
Outcome results
Primary
Number of Participants Reporting Serious Adverse Events (SAEs) After a Booster Dose of Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine
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.
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conv-R/JE Group | Number of Participants Reporting Serious Adverse Events (SAEs) After a Booster Dose of Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine | 2 Participants |
| Acc-R/JE Group | Number of Participants Reporting Serious Adverse Events (SAEs) After a Booster Dose of Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine | 0 Participants |
| Conv-R Group | Number of Participants Reporting Serious Adverse Events (SAEs) After a Booster Dose of Purified Chick Embryo Cell Culture (PCEC) Rabies Vaccine | 3 Participants |
Primary
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
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conv-R/JE Group | 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 |
| Acc-R/JE Group | 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 |
| Conv-R Group | 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 | 2 Participants |
Primary
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 3 and Year 4
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conv-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 3 and Year 4 | 5 Participants |
| Acc-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 3 and Year 4 | 5 Participants |
| Conv-R Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 3 and Year 4 | 7 Participants |
Primary
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 4 and Year 5
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conv-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 4 and Year 5 | 7 Participants |
| Acc-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 4 and Year 5 | 0 Participants |
| Conv-R Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 4 and Year 5 | 4 Participants |
Primary
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 5 and Year 6
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conv-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 5 and Year 6 | 3 Participants |
| Acc-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 5 and Year 6 | 2 Participants |
| Conv-R Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 5 and Year 6 | 10 Participants |
Primary
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 6 and Year 7
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conv-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 6 and Year 7 | 0 Participants |
| Acc-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 6 and Year 7 | 2 Participants |
| Conv-R Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 6 and Year 7 | 0 Participants |
Primary
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 7 and Year 8
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conv-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 7 and Year 8 | 0 Participants |
| Acc-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 7 and Year 8 | 0 Participants |
| Conv-R Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 7 and Year 8 | 0 Participants |
Primary
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 8 and Year 9
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conv-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 8 and Year 9 | 1 Participants |
| Acc-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 8 and Year 9 | 0 Participants |
| Conv-R Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 8 and Year 9 | 2 Participants |
Primary
Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 9 and Year 10
Time frame: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Conv-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 9 and Year 10 | 2 Participants |
| Acc-R/JE Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 9 and Year 10 | 0 Participants |
| Conv-R Group | Number of Participants Who Had Their RNVA Concentrations Drop Below 0.5 IU/mL Between Year 9 and Year 10 | 0 Participants |
Primary
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 10
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conv-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 10 | 56.2 Percentage of participants |
| Acc-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 10 | 62.3 Percentage of participants |
| Conv-R Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 10 | 62.7 Percentage of participants |
Primary
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 3
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conv-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 3 | 81.6 Percentage of participants |
| Acc-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 3 | 78.8 Percentage of participants |
| Conv-R Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 3 | 84.9 Percentage of participants |
Primary
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 4
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conv-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 4 | 74.4 Percentage of participants |
| Acc-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 4 | 70.8 Percentage of participants |
| Conv-R Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 4 | 76.5 Percentage of participants |
Primary
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 5
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conv-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 5 | 66.1 Percentage of participants |
| Acc-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 5 | 69.1 Percentage of participants |
| Conv-R Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 5 | 73.1 Percentage of participants |
Primary
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 6
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conv-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 6 | 60.9 Percentage of participants |
| Acc-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 6 | 66.2 Percentage of participants |
| Conv-R Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 6 | 66.5 Percentage of participants |
Primary
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 7
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conv-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 7 | 60.2 Percentage of participants |
| Acc-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 7 | 64.4 Percentage of participants |
| Conv-R Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 7 | 67.3 Percentage of participants |
Primary
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 8
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conv-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 8 | 59.8 Percentage of participants |
| Acc-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 8 | 64.1 Percentage of participants |
| Conv-R Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 8 | 64.6 Percentage of participants |
Primary
Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 9
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conv-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 9 | 59.3 Percentage of participants |
| Acc-R/JE Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 9 | 63.6 Percentage of participants |
| Conv-R Group | Percentage of Participants With RVNA Concentrations >= 0.5 IU/mL at Year 9 | 64.0 Percentage of participants |
Primary
Percentage of Participants With RVNA Concentrations Greater Than or Equal to (>=) 0.5 IU/mL, 7 Days After 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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Conv-R/JE Group | 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 |
| Acc-R/JE Group | Percentage of Participants With RVNA Concentrations Greater Than or Equal to (>=) 0.5 IU/mL, 7 Days After Booster Dose | 89.1 Percentage of participants |
| Conv-R Group | Percentage of Participants With RVNA Concentrations Greater Than or Equal to (>=) 0.5 IU/mL, 7 Days After Booster Dose | 98.1 Percentage of participants |
Primary
RVNA Antibody Concentrations 7 Days After the Booster Dose
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Conv-R/JE Group | RVNA Antibody Concentrations 7 Days After the Booster Dose | 4.2 IU/mL |
| Acc-R/JE Group | RVNA Antibody Concentrations 7 Days After the Booster Dose | 4.2 IU/mL |
| Conv-R Group | RVNA Antibody Concentrations 7 Days After the Booster Dose | 4.4 IU/mL |
Primary
RVNA Geometric Mean Ratios (GMRs) 7 Days After the Booster Dose Versus Antibody Concentrations Before the Booster Dose
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.
Time frame: 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.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Conv-R/JE Group | RVNA Geometric Mean Ratios (GMRs) 7 Days After the Booster Dose Versus Antibody Concentrations Before the Booster Dose | 23.6 Ratio |
| Acc-R/JE Group | RVNA Geometric Mean Ratios (GMRs) 7 Days After the Booster Dose Versus Antibody Concentrations Before the Booster Dose | 23.4 Ratio |
| Conv-R Group | RVNA Geometric Mean Ratios (GMRs) 7 Days After the Booster Dose Versus Antibody Concentrations Before the Booster Dose | 19.3 Ratio |
Secondary
Rabies Virus Neutralizing Antibody Concentrations
Antibody concentrations were measured in terms of GMCs and expressed in IU/mL.
Time frame: 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.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Conv-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 3 | 1.21 IU/mL |
| Conv-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 4 | 0.69 IU/mL |
| Conv-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 5 | 0.66 IU/mL |
| Conv-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 6 | 0.5 IU/mL |
| Conv-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 7 | 0.49 IU/mL |
| Conv-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 8 | 0.56 IU/mL |
| Conv-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 9 | 0.53 IU/mL |
| Conv-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 10 | 0.59 IU/mL |
| Acc-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 5 | 0.7 IU/mL |
| Acc-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 9 | 0.7 IU/mL |
| Acc-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 6 | 0.6 IU/mL |
| Acc-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 7 | 0.6 IU/mL |
| Acc-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 8 | 0.76 IU/mL |
| Acc-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 3 | 1.16 IU/mL |
| Acc-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 4 | 0.73 IU/mL |
| Acc-R/JE Group | Rabies Virus Neutralizing Antibody Concentrations | Year 10 | 0.72 IU/mL |
| Conv-R Group | Rabies Virus Neutralizing Antibody Concentrations | Year 5 | 0.74 IU/mL |
| Conv-R Group | Rabies Virus Neutralizing Antibody Concentrations | Year 4 | 0.82 IU/mL |
| Conv-R Group | Rabies Virus Neutralizing Antibody Concentrations | Year 3 | 1.3 IU/mL |
| Conv-R Group | Rabies Virus Neutralizing Antibody Concentrations | Year 6 | 0.58 IU/mL |
| Conv-R Group | Rabies Virus Neutralizing Antibody Concentrations | Year 9 | 0.62 IU/mL |
| Conv-R Group | Rabies Virus Neutralizing Antibody Concentrations | Year 8 | 0.68 IU/mL |
| Conv-R Group | Rabies Virus Neutralizing Antibody Concentrations | Year 7 | 0.61 IU/mL |
| Conv-R Group | Rabies Virus Neutralizing Antibody Concentrations | Year 10 | 0.68 IU/mL |
Secondary
Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Conv-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 3 | 100 Cumulative percentage of participants |
| Conv-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 4 | 83 Cumulative percentage of participants |
| Conv-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 5 | 67 Cumulative percentage of participants |
| Conv-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 6 | 54 Cumulative percentage of participants |
| Conv-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 7 | 43 Cumulative percentage of participants |
| Conv-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 8 | 32 Cumulative percentage of participants |
| Conv-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 9 | 21 Cumulative percentage of participants |
| Conv-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 10 | 10 Cumulative percentage of participants |
| Acc-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 5 | 70 Cumulative percentage of participants |
| Acc-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 9 | 22 Cumulative percentage of participants |
| Acc-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 6 | 57 Cumulative percentage of participants |
| Acc-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 7 | 45 Cumulative percentage of participants |
| Acc-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 8 | 33 Cumulative percentage of participants |
| Acc-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 3 | 100 Cumulative percentage of participants |
| Acc-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 4 | 84 Cumulative percentage of participants |
| Acc-R/JE Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 10 | 11 Cumulative percentage of participants |
| Conv-R Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 5 | 69 Cumulative percentage of participants |
| Conv-R Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 4 | 83 Cumulative percentage of participants |
| Conv-R Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 3 | 100 Cumulative percentage of participants |
| Conv-R Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 6 | 56 Cumulative percentage of participants |
| Conv-R Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 9 | 21 Cumulative percentage of participants |
| Conv-R Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 8 | 32 Cumulative percentage of participants |
| Conv-R Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 7 | 44 Cumulative percentage of participants |
| Conv-R Group | Reverse Cumulative Percentage for Participants With RVNA Concentrations >=0.5 IU/mL | Year 10 | 10 Cumulative percentage of participants |