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Safety and Immunogenicity of Two Intradermal Rabies Vaccine Regimens Administered With and Without Human Rabies Immunoglobulin in Subjects ≥ 1 Years of Age

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ClinicalTrials.gov Identifier: NCT02177032
Recruitment Status : Completed
First Posted : June 27, 2014
Results First Posted : April 7, 2017
Last Update Posted : April 7, 2017
Sponsor:
Collaborator:
Novartis Vaccines
Information provided by (Responsible Party):
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Condition Rabies Infection
Interventions Biological: Rabies vaccine
Biological: Rabies vaccines + Rabies immunoglobulins
Enrollment 885
Recruitment Details  
Pre-assignment Details All enrolled subjects were included in the trial.
Arm/Group Title 4-sites, 1-week WITHOUT HRIG 4-sites, 1-week WITH HRIG 2-sites, TRC WITHOUT HRIG 2-sites, TRC WITH HRIG
Hide Arm/Group Description 12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen 12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) to adults only, according to the “4-sites, 1-week” regimen HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight intramuscularly 8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) according to the “2-sites, TRC”, updated Thai Red Cross regimen 8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the “2-sites, TRC”, updated Thai Red Cross regimen. HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight intramuscularly
Period Title: Overall Study
Started 355 88 354 88
Completed 350 86 351 88
Not Completed 5 2 3 0
Reason Not Completed
ADMINISTRATIVE REASON             2             0             1             0
Lost to Follow-up             0             2             0             0
OTHER             2             0             1             0
Withdrawal by Subject             1             0             1             0
Arm/Group Title 4-sites, 1-week WITHOUT HRIG 4-sites, 1-week WITH HRIG 2-sites, TRC WITHOUT HRIG 2-sites, TRC WITH HRIG Total
Hide Arm/Group Description 12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen 12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) to adults only, according to the “4-sites, 1-week” regimen HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight 8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) according to the “2-sites, TRC”, updated Thai Red Cross regimen. 8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the “2-sites, TRC”, updated Thai Red Cross regimen. HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight intramuscularly Total of all reporting groups
Overall Number of Baseline Participants 355 88 354 88 885
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Year
Number Analyzed 355 participants 88 participants 354 participants 88 participants 885 participants
20.0  (15.0) 32.7  (10.8) 20.6  (15.1) 34.4  (11.2) 22.9  (15.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 355 participants 88 participants 354 participants 88 participants 885 participants
FEMALE
202
  56.9%
44
  50.0%
179
  50.6%
51
  58.0%
476
  53.8%
MALE
153
  43.1%
44
  50.0%
175
  49.4%
37
  42.0%
409
  46.2%
1.Primary Outcome
Title Percentages of Subjects With RVNA Titer >= 0.5 and Vaccine Group Differences ("4-sites, 1-week" to That of "2-sites, TRC" ID PEP Regimen of the PCEC Rabies Vaccine With or Without HRIG Administration)
Hide Description

Vaccine group differences are calculated assuming a binomial distribution and the associated confidence interval for the differences in percentage was based on M-N method.

Non-inferiority of the immune response of the new "4-sites, 1-week" ID PEP regimen of the PCEC vaccine, with or without HRIG administration, to that of the currently recommended "2-sites, TRC" ID PEP regimen of the PCEC rabies vaccine with or without HRIG administration, as measured by the percentage of subjects with RVNA titer ≥ 0.5 IU/ml at day 50 in the whole study population.

Time Frame Study day 50 (D50)
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS): all subjects who correctly receive the vaccine doses, provided immunogenicity data at the relevant time points and were not excluded due to reasons defined prior to the analysis.
Arm/Group Title TOTAL 4-sites, 1-week TOTAL 2-sites, TRC
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) to adults only, according to the “4-sites, 1-week” regimen with and without HRIG administered on day 1
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the “2-sites, TRC”, updated Thai Red Cross regimen, with or without HRIG administered on day 1
Overall Number of Participants Analyzed 357 350
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of Subjects
99
(98 to 100)
100
(99 to 100)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority in immune response of the “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen compared to the currently recommended “2-sites TRC” (2-2-2-0-2) ID PEP regimen, with or without HRIG, will be established If the lower bound of the two sided 95% confidence interval around the differences of the percentage of subject with RVNA titer ≥ 0.5 IU/ml at day 50 is > -0.05 (non-inferiority margin).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Protection Rate Differences
Estimated Value -1
Confidence Interval (2-Sided) 95%
-2.4 to 0
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration and Between-group (2 ID Rabies Vaccine Regimens (4-sites, 1-week and 2-sites, TRC) With or Without HRIG) Ratio of GMCs
Hide Description

Immunogenicity was assessed in terms of Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration in Children and Adult Subjects, ≥ 1 Years of Age at day 50 The GMCs, GMRs (i.e., within group ratio) and associated two sided 95% confidence intervals for each group were computed by exponentiating (base 10) of the least square means of the logarithmically transformed (base 10) concentration (and their differences) and the 95% CIs obtained from an Analysis of variance (ANOVA) with vaccine regimen, age strata and center as factors.

Non-inferiority of the immune response between the 2 ID rabies vaccine regimens (4-sites, 1-week and 2-sites, TRC) with or without HRIG administration as measured by RVNA GMCs at day 50 in the whole study population.

Time Frame Study Day 50
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS): all subjects who correctly receive the vaccine doses, provided immunogenicity data at the relevant time points and were not excluded due to reasons defined prior to the analysis
Arm/Group Title TOTAL 4-sites, 1-week TOTAL 2-sites, TRC
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen (i.e. 4 doses of vaccine; in both deltoids and anterolateral thigh areas, administered on days 1, 4, and 8) with or without HRIG administration on day 1
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the “2-sites, TRC”, updated Thai Red Cross regimen, with or without HRIG administered on day 1
Overall Number of Participants Analyzed 357 350
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/mL
4.58
(4.15 to 5.06)
10
(9.29 to 11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The investigational regimen 4-sites, 1-week” ID PEP will be declared as non-inferior to currently recommended “2-sites TRC” ID PEP regimen if the lower bound of the two sided 95% confidence interval around of the observed GMC ratio is greater than 0.667.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Group Ratios
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.37 to 0.58
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Geometric Mean Rabies Virus Neutralizing Antibody Concentration at Days 8, 15, 91, 181 and 366 & Between-group (2 ID Rabies Vaccine Regimens (4-sites,1-week & 2-sites, TRC) With or Without HRIG) Ratio of GMCs in Children & Adult Subjects,≥ 1 Years of Age
Hide Description

Immunogenicity was assessed in terms of the Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration at Days 8, 15, 91, 181 and 366 in Children and Adult Subjects, ≥ 1 Years of Age The GMCs, GMRs (i.e., within group ratio) and associated two sided 95% confidence intervals for each group were computed by exponentiating (base 10) of the least square means of the logarithmically transformed (base 10) concentration (and their differences) and the 95% CIs obtained from an Analysis of variance (ANOVA) with vaccine regimen, age strata and center as factors.

Non-inferiority of the immune response between the 2 ID rabies vaccine regimens (4-sites, 1-week and 2-sites, TRC) with or without HRIG administration as measured by RVNA GMCs at day 50 in the whole study population.

Time Frame At Days 8, 15, 91, 181 and 366
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS): all subjects who correctly receive the vaccine doses, provided immunogenicity data at the relevant time points and were not excluded due to reasons defined prior to the analysis.
Arm/Group Title TOTAL 4-sites, 1-week TOTAL 2-sites, TRC
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen (i.e. 4 doses of vaccine; in both deltoids and anterolateral thigh areas, administered on days 1, 4, and 8) with or without HRIG administration on day 1
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the “2-sites, TRC”, updated Thai Red Cross regimen, with or without HRIG administered on day 1
Overall Number of Participants Analyzed 363 362
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/mL
Day 8 (N= 363, 362)
0.23
(0.21 to 0.25)
0.14
(0.13 to 0.15)
Day 15 (N= 357, 361)
18
(17 to 20)
12
(10 to 13)
Day 91 (N= 358, 362)
2.32
(2.09 to 2.56)
3.68
(3.32 to 4.07)
Day 181 (N= 357, 360)
1.59
(1.41 to 1.78)
1.44
(1.28 to 1.62)
Day 366 (N= 356, 352)
1.59
(1.41 to 1.79)
1.14
(1.01 to 1.28)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The investigational regimen 4-sites, 1-week” ID PEP will be declared as non-inferior to currently recommended “2-sites TRC” ID PEP regimen if the lower bound of the two sided 95% confidence interval around of the observed GMC ratio is greater than 0.667 (Day 8)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Group Ratios
Estimated Value 1.04
Confidence Interval (2-Sided) 95%
0.84 to 1.29
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The investigational regimen 4-sites, 1-week” ID PEP will be declared as non-inferior to currently recommended “2-sites TRC” ID PEP regimen if the lower bound of the two sided 95% confidence interval around of the observed GMC ratio is greater than 0.667 (Day 15)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Group Ratios
Estimated Value 1.68
Confidence Interval (2-Sided) 95%
1.35 to 2.1
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The investigational regimen 4-sites, 1-week” ID PEP will be declared as non-inferior to currently recommended “2-sites TRC” ID PEP regimen if the lower bound of the two sided 95% confidence interval around of the observed GMC ratio is greater than 0.667 (Day 91).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Group Ratios
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.54 to 0.85
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The investigational regimen 4-sites, 1-week” ID PEP will be declared as non-inferior to currently recommended “2-sites TRC” ID PEP regimen if the lower bound of the two sided 95% confidence interval around of the observed GMC ratio is greater than 0.667 (Day 181)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Group Ratios
Estimated Value 1.22
Confidence Interval (2-Sided) 95%
0.94 to 1.59
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The investigational regimen 4-sites, 1-week” ID PEP will be declared as non-inferior to currently recommended “2-sites TRC” ID PEP regimen if the lower bound of the two sided 95% confidence interval around of the observed GMC ratio is greater than 0.667 (Day 366)
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Vaccine Group Ratios
Estimated Value 1.67
Confidence Interval (2-Sided) 95%
1.27 to 2.19
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL at Days 8, 15, 91, 181 and 366 in Children and Adult Subjects and Vaccine Group Differences (2 ID Rabies Vaccine Regimens (4-sites, 1-week and 2-sites, TRC), With or Without HRIG), ≥ 1 Years of Age
Hide Description

Vaccine group differences are calculated assuming a binomial distribution and the associated confidence interval for the differences in percentage was based on M-N method.

RVNA percentage of subjects with RVNA titer ≥ 0.5 IU/mL at study days 8, 15, 91, 181, and 366 following administration of the 2 ID rabies vaccine regimens (4-sites, 1-week and 2-sites, TRC), with or without HRIG, in the whole study population.

Time Frame At Days 8, 15, 91, 181 and 366
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS): all subjects who correctly receive the vaccine doses, provided immunogenicity data at the relevant time points and were not excluded due to reasons defined prior to the analysis.
Arm/Group Title TOTAL 4-sites, 1-week TOTAL 2-sites, TRC
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen (i.e. 4 doses of vaccine; in both deltoids and anterolateral thigh areas, administered on days 1, 4, and 8) with or without HRIG administration on day 1
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the “2-sites, TRC”, updated Thai Red Cross regimen, with or without HRIG administered on day 1
Overall Number of Participants Analyzed 363 362
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of Subjects
Day 8 (N= 363, 362)
18
(15 to 23)
10
(7 to 13)
Day 15 (N= 357, 361)
100
(99 to 100)
100
(98 to 100)
Day 91 (N= 358, 362)
96
(94 to 98)
99
(98 to 100)
Day 181 (N= 357, 360)
93
(90 to 95)
93
(90 to 96)
Day 366 (N= 356, 352)
90
(86 to 93)
83
(79 to 87)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority in immune response of the “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen compared to the currently recommended “2-sites TRC” (2-2-2-0-2) ID PEP regimen, with or without HRIG, will be established If the lower bound of the two sided 95% confidence interval around the differences of the percentage of subject with RVNA titer ≥ 0.5 IU/ml at Day 8 is > -0.05 (non-inferiority margin).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Protection Rate Differences
Estimated Value 9
Confidence Interval (2-Sided) 95%
3.8 to 13.9
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority in immune response of the “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen compared to the currently recommended “2-sites TRC” (2-2-2-0-2) ID PEP regimen, with or without HRIG, will be established If the lower bound of the two sided 95% confidence interval around the differences of the percentage of subject with RVNA titer ≥ 0.5 IU/ml at Day 15 is > -0.05 (non-inferiority margin).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Protection Rate Differences
Estimated Value 0
Confidence Interval (2-Sided) 95%
-1 to 1.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority in immune response of the “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen compared to the currently recommended “2-sites TRC” (2-2-2-0-2) ID PEP regimen, with or without HRIG, will be established If the lower bound of the two sided 95% confidence interval around the differences of the percentage of subject with RVNA titer ≥ 0.5 IU/ml at Day 91 is > -0.05 (non-inferiority margin).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Protection Rate Differences
Estimated Value -3
Confidence Interval (2-Sided) 95%
-6 to -1.4
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority in immune response of the “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen compared to the currently recommended “2-sites TRC” (2-2-2-0-2) ID PEP regimen, with or without HRIG, will be established If the lower bound of the two sided 95% confidence interval around the differences of the percentage of subject with RVNA titer ≥ 0.5 IU/ml at Day 181 is > -0.05 (non-inferiority margin).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Protection Rate Differences
Estimated Value -1
Confidence Interval (2-Sided) 95%
-4.5 to 3.2
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection TOTAL 4-sites, 1-week, TOTAL 2-sites, TRC
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority in immune response of the “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen compared to the currently recommended “2-sites TRC” (2-2-2-0-2) ID PEP regimen, with or without HRIG, will be established If the lower bound of the two sided 95% confidence interval around the differences of the percentage of subject with RVNA titer ≥ 0.5 IU/ml at Day 366 is > -0.05 (non-inferiority margin).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Protection Rate Differences
Estimated Value 6
Confidence Interval (2-Sided) 95%
1.3 to 11.5
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration and Vaccine Group Differences in Adult Subjects, ≥ 18 Years of Age
Hide Description

Immunogenicity was assessed in terms of the Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration at Days 8, 15, 50,91, 181 and 366 in Adult Subjects, ≥ 18 Years of Age.

RVNA GMCs with RVNA titer ≥ 0.5 IU/mL at days 8, 15, 50, 91, 181 and 366 and group differences (4-sites,1-week without HRIG versus 4-sites,1-week with HRIG; 4-sites,1-week with HRIG versus 2-sites,TRC with HRIG; 4-sites,1-week without HRIG versus 2-sites, TRC without HRIG)

Time Frame At Days 8, 15, 50, 91, 181 and 366
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS): all subjects who correctly receive the vaccine doses, provided immunogenicity data at the relevant time points and were not excluded due to reasons defined prior to the analysis. This outcome measure is applicable only for the 4-sites, 1-week with HRIG and 4-sites, 1-week without HRIG Groups.
Arm/Group Title 4-sites, 1-week WITH HRIG 4-sites, 1-week WITHOUT HRIG
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) to adults only, according to the “4-sites, 1-week” regimen with HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen
Overall Number of Participants Analyzed 66 150
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/mL
Day 8 (N= 66, 150)
0.21
(0.17 to 0.26)
0.15
(0.13 to 0.17)
Day 15 (N= 65, 146)
13
(11 to 15)
15
(13 to 17)
Day 50 (N= 65, 146)
1.97
(1.6 to 2.43)
4.47
(3.9 to 5.13)
Day 91 (N= 65, 149)
1.01
(0.81 to 1.27)
2.28
(1.96 to 2.65)
Day 181 (N= 65, 146)
0.88
(0.67 to 1.14)
1.92
(1.61 to 2.29)
Day 366 (N= 65, 145)
0.68
(0.53 to 0.88)
1.42
(1.19 to 1.69)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 4-sites, 1-week WITH HRIG, 4-sites, 1-week WITHOUT HRIG
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority in immune response of the “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen of the PCEC vaccine, with HRIG administration, compared to that of the new “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen of the PCEC vaccine, without HRIG administration, in adult subjects will be established if the lower bound of the two sided 95% confidence interval around the differences of the percentage of subject with RVNA titer ≥ 0.5 IU/ml at Day 8 is > -0.05 (non-inferiority margin).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Protection Rate Differences
Estimated Value -11
Confidence Interval (2-Sided) 95%
-19.6 to -1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection 4-sites, 1-week WITH HRIG, 4-sites, 1-week WITHOUT HRIG
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority in immune response of the “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen of the PCEC vaccine, with HRIG administration, compared to that of the new “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen of the PCEC vaccine, without HRIG administration, in adult subjects will be established if the lower bound of the two sided 95% confidence interval around the differences of the percentage of subject with RVNA titer ≥ 0.5 IU/ml at Day 15 is > -0.05 (non-inferiority margin).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Protection Rate Differences
Estimated Value 0
Confidence Interval (2-Sided) 95%
-5.6 to 2.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 4-sites, 1-week WITH HRIG, 4-sites, 1-week WITHOUT HRIG
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority in immune response of the “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen of the PCEC vaccine, with HRIG administration, compared to that of the new “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen of the PCEC vaccine, without HRIG administration, in adult subjects will be established if the lower bound of the two sided 95% confidence interval around the differences of the percentage of subject with RVNA titer ≥ 0.5 IU/ml at Day 91 is > -0.05 (non-inferiority margin).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Protection Rate Differences
Estimated Value -15
Confidence Interval (2-Sided) 95%
-26 to -7.1
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection 4-sites, 1-week WITH HRIG, 4-sites, 1-week WITHOUT HRIG
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority in immune response of the “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen of the PCEC vaccine, with HRIG administration, compared to that of the new “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen of the PCEC vaccine, without HRIG administration, in adult subjects will be established if the lower bound of the two sided 95% confidence interval around the differences of the percentage of subject with RVNA titer ≥ 0.5 IU/ml at Day 181 is > -0.05 (non-inferiority margin).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Protection Rate Differences
Estimated Value -17
Confidence Interval (2-Sided) 95%
-29 to -7.1
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 4-sites, 1-week WITH HRIG, 4-sites, 1-week WITHOUT HRIG
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments The non-inferiority in immune response of the “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen of the PCEC vaccine, with HRIG administration, compared to that of the new “4-sites, 1-week” (4-4-4-0-0) ID PEP regimen of the PCEC vaccine, without HRIG administration, in adult subjects will be established if the lower bound of the two sided 95% confidence interval around the differences of the percentage of subject with RVNA titer ≥ 0.5 IU/ml at Day 366 is > -0.05 (non-inferiority margin).
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Protection Rate Differences
Estimated Value -25
Confidence Interval (2-Sided) 95%
-37.8 to -13.2
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Adult Subjects, ≥ 18 Years of Age
Hide Description

Immunogenicity was assessed in terms of the Percentages of Subjects With Anti-RVNA concentration ≥0.5 IU/mL at Days 8, 15, 50, 91, 181 and 366 in Adult Subjects, ≥ 18 Years of Age.

Percentage of subjects with RVNA titer ≥ 0.5 IU/mL at days 8, 15, 50, 91, 181 and 366 and group differences (4-sites,1-week without HRIG versus 4-sites,1-week with HRIG; 4-sites,1-week with HRIG versus 2-sites,TRC with HRIG; 4-sites,1-week without HRIG versus 2-sites, TRC without HRIG)

Time Frame At Days 8, 15,50, 91, 181 and 366
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS): all subjects who correctly receive the vaccine doses, provided immunogenicity data at the relevant time points and were not excluded due to reasons defined prior to the analysis. This outcome measure is applicable only for the 4-sites, 1-week with HRIG and 4-sites, 1-week without HRIG Groups.
Arm/Group Title 4-sites, 1-week WITH HRIG 4-sites, 1-week WITHOUT HRIG
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) to adults only, according to the “4-sites, 1-week” regimen HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen
Overall Number of Participants Analyzed 66 151
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of Subjects
Day 1 (N= 66, 151)
0
(0 to 5)
0
(0 to 2)
Day 8 (N= 66, 150)
8
(3 to 17)
19
(13 to 26)
Day 15 (N= 65, 146)
100
(94 to 100)
100
(98 to 100)
Day 50 (N= 65, 146)
95
(87 to 99)
100
(98 to 100)
Day 91 (N= 65, 149)
83
(72 to 91)
98
(94 to 100)
Day 181 (N= 65, 146)
77
(65 to 86)
94
(89 to 97)
Day 366 (N= 65, 145)
66
(53 to 77)
91
(85 to 95)
7.Secondary Outcome
Title Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration in Children and Adult Subjects, ≥ 1 Years of Age
Hide Description Immunogenicity was assessed in terms of the Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration at Days 8, 15, 50, 91, 181 and 366 in Children and Adult Subjects, ≥ 1 Years of Age
Time Frame At Days 8, 15, 50, 91, 181 and 366
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS): all subjects who correctly receive the vaccine doses, provided immunogenicity data at the relevant time points and were not excluded due to reasons defined prior to the analysis. This outcome measure is applicable only for the 4-sites, 1-week without HRIG and 2-sites, TRC without HRIG Groups.
Arm/Group Title 4-sites, 1-week Without HRIG 2-sites, TRC Without HRIG
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) according to the “2-sites, TRC”, updated Thai Red Cross regimen.
Overall Number of Participants Analyzed 298 290
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/mL
Day 1 (N=298, 290)
0.05
(0.05 to 0.05)
0.05
(0.05 to 0.05)
Day 8 (N= 297, 290)
0.23
(0.21 to 0.25)
0.13
(0.12 to 0.14)
Day 15 (N= 292, 289)
19
(17 to 21)
12
(11 to 13)
Day 50 (N= 292, 281)
5.04
(4.56 to 5.57)
10
(9.48 to 12)
Day 91 (N= 293, 290)
2.54
(2.29 to 2.82)
3.8
(3.42 to 4.21)
Day 181 (N= 292, 289)
1.73
(1.53 to 1.95)
1.5
(1.32 to 1.69)
Day 366 (N= 291, 283)
1.73
(1.53 to 1.95)
1.2
(1.06 to 1.36)
8.Secondary Outcome
Title Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Children and Adult Subjects, ≥ 1 Years of Age
Hide Description Immunogenicity was assessed in terms of the Percentages of Subjects With Anti-RVNA concentration ≥0.5 IU/mL at Days 8, 15, 50, 91, 181 and 366 in Children and Adult Subjects, ≥ 1 Years of Age
Time Frame At Days 8, 15, 50, 91, 181 and 366
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS): all subjects who correctly receive the vaccine doses, provided immunogenicity data at the relevant time points and were not excluded due to reasons defined prior to the analysis. This outcome measure is only applicable for the 4-sites, 1-week without HRIG and 2-sites, TRC without HRIG Groups.
Arm/Group Title 4-sites, 1-week Without HRIG 2-sites, TRC Without HRIG
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) according to the “2-sites, TRC”, updated Thai Red Cross regimen.
Overall Number of Participants Analyzed 298 290
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of Subjects
Day 8 (N= 297, 290)
21
(16 to 26)
10
(7 to 14)
Day 15 (N= 292, 289)
100
(99 to 100)
100
(99 to 100)
Day 50 (N= 292, 281)
100
(99 to 100)
100
(99 to 100)
Day 91 (N= 293, 290)
99
(97 to 100)
100
(98 to 100)
Day 181 (N= 292, 289)
96
(93 to 98)
96
(92 to 98)
Day 366 (N= 291, 283)
95
(92 to 97)
87
(82 to 90)
9.Secondary Outcome
Title Number of Subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination
Hide Description Number of subjects Who Reported Solicited Local and Systemic Adverse Events After Any Vaccination
Time Frame From day 1 to day 3; from day 4 to day 7; from day 8 to day 14; from day 29 to day 35(2-sites, TRC PEP, ID regimen)
Hide Outcome Measure Data
Hide Analysis Population Description
Solicited Safety Set- All subjects in the Exposed Population who provide post vaccination solicited adverse event data. The number of exposed set participants analyzed for safety is different from the Per Protocol Set (PPS) for immunogenicity.
Arm/Group Title 4-sites, 1-week WITHOUT HRIG 4-sites, 1-week WITH HRIG 2-sites, TRC WITHOUT HRIG 2-sites, TRC WITH HRIG
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) to adults only, according to the “4-sites, 1-week” regimen HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) according to the “2-sites, TRC”, updated Thai Red Cross regimen.
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the “2-sites, TRC”, updated Thai Red Cross regimen. HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight intramuscularly
Overall Number of Participants Analyzed 356 85 353 89
Measure Type: Number
Unit of Measure: Subjects
Injection site erythema(≥ 1 to ≤ 5 Y); Day 1 0 NA [1]  0 NA [1] 
Injection site erythema(≥ 1 to ≤ 5 Y); Day 4 0 NA [1]  0 NA [1] 
Injection site erythema(≥ 1 to ≤ 5 Y); Day 8 1 NA [1]  0 NA [1] 
Injection site erythema(≥ 1 to ≤ 5 Y); Day 29 NA [2]  NA [1]  2 NA [1] 
Injection site induration(≥ 1 to ≤ 5 Y); Day 1 0 NA [1]  0 NA [1] 
Injection site induration(≥ 1 to ≤ 5 Y); Day 4 0 NA [1]  0 NA [1] 
Injection site induration(≥ 1 to ≤ 5 Y); Day 8 0 NA [1]  0 NA [1] 
Injection site induration(≥ 1 to ≤ 5 Y); Day 29 NA [2]  NA [1]  1 NA [1] 
Injection site swelling (≥ 1 to ≤ 5 Y); Day 1 0 NA [1]  0 NA [1] 
Injection site swelling (≥ 1 to ≤ 5 Y); Day 4 0 NA [1]  0 NA [1] 
Injection site swelling (≥ 1 to ≤ 5 Y); Day 8 0 NA [1]  2 NA [1] 
Injection site swelling (≥ 1 to ≤ 5 Y); Day 29 NA [2]  NA [1]  8 NA [1] 
Injection site erythema (≥ 6 to ≤ 17 Y); Day 1 0 NA [1]  0 NA [1] 
Injection site erythema (≥ 6 to ≤ 17 Y); Day 4 0 NA [1]  0 NA [1] 
Injection site erythema (≥ 6 to ≤ 17 Y); Day 8 1 NA [1]  2 NA [1] 
Injection site erythema (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  8 NA [1] 
Injection site induration (≥ 6 to ≤ 17 Y); Day 1 0 NA [1]  0 NA [1] 
Injection site induration (≥ 6 to ≤ 17 Y); Day 4 1 NA [1]  0 NA [1] 
Injection site induration (≥ 6 to ≤ 17 Y); Day 8 0 NA [1]  1 NA [1] 
Injection site induration (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  2 NA [1] 
Injection site swelling (≥ 6 to ≤ 17 Y); Day 1 0 NA [1]  0 NA [1] 
Injection site swelling (≥ 6 to ≤ 17 Y); Day 4 1 NA [1]  0 NA [1] 
Injection site swelling (≥ 6 to ≤ 17 Y); Day 8 0 NA [1]  2 NA [1] 
Injection site swelling (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  2 NA [1] 
Injection site erythema (≥ 18 Y); Day 1 3 6 2 3
Injection site erythema (≥ 18 Y); Day 4 11 4 4 5
Injection site erythema (≥ 18 Y); Day 8 12 1 8 4
Injection site erythema (≥ 18 Y); Day 29 NA [2]  NA [2]  27 13
Injection site induration (≥ 18 Y); Day 1 0 0 0 0
Injection site induration (≥ 18 Y); Day 4 0 0 0 0
Injection site induration (≥ 18 Y); Day 8 2 0 2 0
Injection site induration (≥ 18 Y); Day 29 NA [2]  NA [2]  4 1
Injection site swelling (≥ 18 Y); Day 1 0 0 1 0
Injection site swelling (≥ 18 Y); Day 4 0 0 0 0
Injection site swelling (≥ 18 Y); Day 8 0 0 2 0
Injection site swelling (≥ 18 Y); Day 29 NA [2]  NA [2]  5 1
Change In Eating Habits,( ≥ 1 to ≤ 5 Y); Day 1 4 NA [1]  3 NA [1] 
Change In Eating Habits,( ≥ 1 to ≤ 5 Y); Day 4 3 NA [1]  1 NA [1] 
Change In Eating Habits,( ≥ 1 to ≤ 5 Y); Day 8 3 NA [1]  2 NA [1] 
Change In Eating Habits,( ≥ 1 to ≤ 5 Y); Day 29 NA [2]  NA [1]  6 NA [1] 
Sleepiness (≥ 1 to ≤ 5 Y); Day 1 4 NA [1]  7 NA [1] 
Sleepiness (≥ 1 to ≤ 5 Y); Day 4 7 NA [1]  3 NA [1] 
Sleepiness (≥ 1 to ≤ 5 Y); Day 8 2 NA [1]  4 NA [1] 
Sleepiness (≥ 1 to ≤ 5 Y); Day 29 NA [2]  NA [1]  2 NA [1] 
Vomiting (≥ 1 to ≤ 5 Y); Day 1 4 NA [1]  1 NA [1] 
Vomiting (≥ 1 to ≤ 5 Y); Day 4 2 NA [1]  1 NA [1] 
Vomiting (≥ 1 to ≤ 5 Y); Day 8 1 NA [1]  0 NA [1] 
Vomiting (≥ 1 to ≤ 5 Y); Day 29 NA [2]  NA [1]  5 NA [1] 
Diarrhea (≥ 1 to ≤ 5 Y); Day 1 3 NA [1]  2 NA [1] 
Diarrhea (≥ 1 to ≤ 5 Y); Day 4 2 NA [1]  2 NA [1] 
Diarrhea (≥ 1 to ≤ 5 Y); Day 8 4 NA [1]  1 NA [1] 
Diarrhea (≥ 1 to ≤ 5 Y); Day 29 NA [2]  NA [1]  4 NA [1] 
Irritability.( ≥ 1 to ≤ 5 Y); Day 1 5 NA [1]  3 NA [1] 
Irritability.( ≥ 1 to ≤ 5 Y); Day 4 3 NA [1]  3 NA [1] 
Irritability.( ≥ 1 to ≤ 5 Y); Day 8 1 NA [1]  5 NA [1] 
Irritability.( ≥ 1 to ≤ 5 Y); Day 29 NA [2]  NA [1]  5 NA [1] 
Chills(≥ 6 to ≤ 17 Y); Day 1 2 NA [1]  2 NA [1] 
Chills(≥ 6 to ≤ 17 Y); Day 4 0 NA [1]  1 NA [1] 
Chills(≥ 6 to ≤ 17 Y); Day 8 1 NA [1]  1 NA [1] 
Chills(≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  0 NA [1] 
Nausea ( ≥ 6 to ≤ 17 Y); Day 1 4 NA [1]  3 NA [1] 
Nausea ( ≥ 6 to ≤ 17 Y); Day 4 2 NA [1]  1 NA [1] 
Nausea ( ≥ 6 to ≤ 17 Y); Day 8 3 NA [1]  1 NA [1] 
Nausea ( ≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  0 NA [1] 
Generalized Myalgia (≥ 6 to ≤ 17 Y); Day 1 5 NA [1]  1 NA [1] 
Generalized Myalgia (≥ 6 to ≤ 17 Y); Day 4 4 NA [1]  2 NA [1] 
Generalized Myalgia (≥ 6 to ≤ 17 Y); Day 8 2 NA [1]  3 NA [1] 
Generalized Myalgia (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  4 NA [1] 
Generalized Arthralgia (≥ 6 to ≤ 17 Y); Day 1 3 NA [1]  1 NA [1] 
Generalized Arthralgia (≥ 6 to ≤ 17 Y); Day 4 1 NA [1]  1 NA [1] 
Generalized Arthralgia (≥ 6 to ≤ 17 Y); Day 8 4 NA [1]  2 NA [1] 
Generalized Arthralgia (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  1 NA [1] 
Headache (≥ 6 to ≤ 17 Y); Day 1 8 NA [1]  9 NA [1] 
Headache (≥ 6 to ≤ 17 Y); Day 4 8 NA [1]  8 NA [1] 
Headache (≥ 6 to ≤ 17 Y); Day 8 6 NA [1]  6 NA [1] 
Headache (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  3 NA [1] 
Fatigue (≥ 6 to ≤ 17 Y); Day 1 8 NA [1]  7 NA [1] 
Fatigue (≥ 6 to ≤ 17 Y); Day 4 5 NA [1]  1 NA [1] 
Fatigue (≥ 6 to ≤ 17 Y); Day 8 1 NA [1]  6 NA [1] 
Fatigue (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  6 NA [1] 
Rash (≥ 6 to ≤ 17 Y); Day 1 4 NA [1]  0 NA [1] 
Rash (≥ 6 to ≤ 17 Y); Day 4 3 NA [1]  3 NA [1] 
Rash (≥ 6 to ≤ 17 Y); Day 8 3 NA [1]  3 NA [1] 
Rash (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  2 NA [1] 
Vomitting (≥ 6 to ≤ 17 Y); Day 1 3 NA [1]  5 NA [1] 
Vomitting (≥ 6 to ≤ 17 Y); Day 4 2 NA [1]  1 NA [1] 
Vomitting (≥ 6 to ≤ 17 Y); Day 8 3 NA [1]  2 NA [1] 
Vomitting (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  1 NA [1] 
Diarrhea (≥ 6 to ≤ 17 Y); Day 1 4 NA [1]  2 NA [1] 
Diarrhea (≥ 6 to ≤ 17 Y); Day 4 0 NA [1]  1 NA [1] 
Diarrhea (≥ 6 to ≤ 17 Y); Day 8 1 NA [1]  0 NA [1] 
Diarrhea (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  0 NA [1] 
Loss Of Appetite (≥ 6 to ≤ 17 Y); Day 1 6 NA [1]  3 NA [1] 
Loss Of Appetite (≥ 6 to ≤ 17 Y); Day 4 3 NA [1]  1 NA [1] 
Loss Of Appetite (≥ 6 to ≤ 17 Y); Day 8 1 NA [1]  1 NA [1] 
Loss Of Appetite (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  0 NA [1] 
Chills (≥ 18 Y); Day 1 8 3 5 2
Chills (≥ 18 Y); Day 4 1 2 6 4
Chills (≥ 18 Y); Day 8 5 0 4 0
Chills (≥ 18 Y); Day 29 NA [2]  NA [2]  0 0
Nausea,( ≥ 18 Y); Day 1 8 3 3 3
Nausea,( ≥ 18 Y); Day 4 4 2 2 3
Nausea,( ≥ 18 Y); Day 8 4 0 4 3
Nausea,( ≥ 18 Y); Day 29 NA [2]  NA [2]  0 0
Generalized Myalgia (≥ 18 Y); Day 1 23 12 19 12
Generalized Myalgia (≥ 18 Y); Day 4 16 7 12 6
Generalized Myalgia (≥ 18 Y); Day 8 20 5 15 9
Generalized Myalgia (≥ 18 Y); Day 29 NA [2]  NA [2]  7 4
Generalized Arthralgia (≥ 18 Y); Day 1 18 7 13 7
Generalized Arthralgia (≥ 18 Y); Day 4 6 5 10 7
Generalized Arthralgia (≥ 18 Y); Day 8 15 3 15 6
Generalized Arthralgia (≥ 18 Y); Day 29 NA [2]  NA [2]  6 4
Headache (≥ 18 Y); Day 1 24 6 11 13
Headache (≥ 18 Y); Day 4 14 10 15 11
Headache (≥ 18 Y); Day 8 19 8 15 16
Headache (≥ 18 Y); Day 29 NA [2]  NA [2]  12 11
Fatigue (≥ 18 Y); Day 1 28 11 19 10
Fatigue (≥ 18 Y); Day 4 21 6 17 11
Fatigue (≥ 18 Y); Day 8 19 8 15 14
Fatigue (≥ 18 Y); Day 29 NA [2]  NA [2]  9 10
Rash (≥ 18 Y); Day 1 10 3 4 0
Rash (≥ 18 Y); Day 4 4 3 8 4
Rash (≥ 18 Y); Day 8 6 4 11 2
Rash (≥ 18 Y); Day 29 NA [2]  NA [2]  2 2
Vomitting (≥ 18 Y); Day 1 0 0 2 0
Vomitting (≥ 18 Y); Day 4 0 1 1 1
Vomitting (≥ 18 Y); Day 8 1 0 1 3
Vomitting (≥ 18 Y); Day 29 NA [2]  NA [2]  1 0
Diarrhea (≥ 18 Y); Day 1 5 4 2 5
Diarrhea (≥ 18 Y); Day 4 3 2 5 3
Diarrhea (≥ 18 Y); Day 8 5 1 4 4
Diarrhea (≥ 18 Y); Day 29 NA [2]  NA [2]  3 0
Loss Of Appetite (≥ 18 Y); Day 1 7 0 5 2
Loss Of Appetite (≥ 18 Y); Day 4 3 2 2 0
Loss Of Appetite (≥ 18 Y); Day 8 3 3 2 4
Loss Of Appetite (≥ 18 Y); Day 29 NA [2]  NA [2]  1 1
Injection site tenderness (≥ 1 to ≤ 5 Y); Day 1 15 NA [1]  8 NA [1] 
Injection site tenderness (≥ 1 to ≤ 5 Y); Day 4 8 NA [1]  9 NA [1] 
Injection site tenderness (≥ 1 to ≤ 5 Y); Day 8 7 NA [1]  8 NA [1] 
Injection site tenderness (≥ 1 to ≤ 5 Y); Day 29 NA [2]  NA [1]  9 NA [1] 
Injection site pain (≥ 6 to ≤ 17 Y); Day 1 14 NA [1]  7 NA [1] 
Injection site pain (≥ 6 to ≤ 17 Y); Day 4 6 NA [1]  10 NA [1] 
Injection site pain (≥ 6 to ≤ 17 Y); Day 8 6 NA [1]  11 NA [1] 
Injection site pain (≥ 6 to ≤ 17 Y); Day 29 NA [2]  NA [1]  6 NA [1] 
Injection site pain (≥ 18 Y); Day 1 12 6 16 11
Injection site pain (≥ 18 Y); Day 4 8 8 13 3
Injection site pain (≥ 18 Y); Day 8 8 7 21 3
Injection site pain (≥ 18 Y); Day 29 NA [2]  NA [2]  14 9
[1]
No data as only adults to be enrolled to this group
[2]
Not assessed at Day 29 for this group
10.Secondary Outcome
Title Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Hide Description Safety was assessed in terms of the Number of Subjects Reporting Unsolicited Adverse Events (AEs)
Time Frame Day 1 to Day 366
Hide Outcome Measure Data
Hide Analysis Population Description
Unsolicited Safety Set- All subjects in the Exposed Population who have post vaccination unsolicited adverse event records. The number of exposed set participants analyzed for safety is different from the Per Protocol Set (PPS) for immunogenicity.
Arm/Group Title 4-sites, 1-week WITHOUT HRIG 4-sites, 1-week WITH HRIG 2-sites, TRC WITHOUT HRIG 2-sites, TRC WITH HRIG
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) to adults only, according to the “4-sites, 1-week” regimen HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) according to the “2-sites, TRC”, updated Thai Red Cross regimen
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the “2-sites, TRC”, updated Thai Red Cross regimen. HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight intramuscularly
Overall Number of Participants Analyzed 356 85 353 89
Measure Type: Number
Unit of Measure: Subjects
≥ 1 to ≤ 5 Y Any AEs;D1-366 45 NA [1]  53 NA [1] 
≥ 1 to ≤ 5 Y SAE;D1-366 3 NA [1]  4 NA [1] 
≥ 1 to ≤ 5 Y At least possibly related SAEs;D1-366 0 NA [1]  0 NA [1] 
≥ 1 to ≤ 5 Y Deaths;D1-366 0 NA [1]  0 NA [1] 
≥1 to ≤ 5 Y Withdrawal from study due to AE;D1-366 0 NA [1]  0 NA [1] 
≥ 6 to ≤ 17 Y Any AEs;D1-366 58 NA [1]  71 1
≥ 6 to ≤ 17 Y SAE;D1-366 1 NA [1]  3 NA [1] 
≥6 to ≤ 17 Y At least possibly related SAEs;D1-366 0 NA [1]  0 NA [1] 
≥ 6 to ≤ 17 Y Deaths;D1-366 0 NA [1]  0 NA [1] 
≥6 to ≤17 Y Withdrawal from study due to AE;D1-366 0 NA [1]  0 NA [1] 
≥ 18 Y Any AEs;D1-366 157 71 156 72
≥ 18 Y SAE;D1-366 8 3 7 5
≥ 18 Y At least possibly related SAEs;D1-366 0 0 0 0
≥ 18 Y Deaths;D1-366 0 0 0 0
≥ 18 Y Withdrawal from study due to AE;D1-366 0 0 0 0
Overall population ≥ 1 Y Any AEs;D1-366 260 71 280 73
Overall population ≥ 1 Y SAE;D1-366 12 3 14 5
Overall ≥1Y Atleast possibly related SAEs;D1-366 0 0 0 0
Overall population ≥ 1 Y Deaths;D1-366 0 0 0 0
Overall population ≥1Y Withdrawal due to AE;D1-366 0 0 0 0
[1]
No data as only adults to be enrolled to this group
11.Secondary Outcome
Title Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration ≥0.5 IU/mL and Vaccine Group Differences in Adult Subjects, ≥ 18 Years of Age
Hide Description Immunogenicity was assessed in terms of the Geometric Mean Rabies Virus Neutralizing Antibody (RVNA) Concentration ≥0.5 IU/mL at Days 8, 15, 50,91, 181 and 366 in Adult Subjects, ≥ 18 Years of Age
Time Frame At Days 8, 15, 50, 91, 181 and 366
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS): all subjects who correctly receive the vaccine doses, provided immunogenicity data at the relevant time points and were not excluded due to reasons defined prior to the analysis. This outcome measure is applicable only for 4-sites, 1-week with HRIG and 2-sites TRC with HRIG Groups.
Arm/Group Title 4-sites, 1-week WITH HRIG 2-sites TRC WITH HRIG
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) to adults only, according to the “4-sites, 1-week” regimen HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the “2-sites, TRC”, updated Thai Red Cross regimen, with or without HRIG administered on day 1
Overall Number of Participants Analyzed 66 72
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/mL
Day 1 (N= 66, 72)
0.05
(0.05 to 0.05)
0.05
(0.05 to 0.05)
Day 8 (N= 66, 72)
0.21
(0.17 to 0.26)
0.17
(0.14 to 0.21)
Day 15 (N= 65, 72)
13
(11 to 15)
8.37
(6.96 to 10)
Day 50 (N= 65, 69)
1.97
(1.6 to 2.43)
6.37
(5.21 to 7.78)
Day 91 (N= 65, 72)
1.01
(0.81 to 1.27)
2.25
(1.81 to 2.79)
Day 181 (N= 65, 71)
0.88
(0.67 to 1.14)
1.05
(0.81 to 1.35)
Day 366 (N= 65, 69)
0.68
(0.53 to 0.88)
0.59
(0.46 to 0.76)
12.Secondary Outcome
Title Percentages of Subjects With Anti-RVNA Titer ≥0.5 IU/mL in Adult Subjects, ≥ 18 Years of Age
Hide Description Immunogenicity was assessed in terms of the number of subjects With Anti-RVNA concentration ≥0.5 IU/mL at Days 8, 15, 50, 91, 181 and 366 in Adult Subjects, ≥ 18 Years of Age
Time Frame At Days 8, 15,50, 91, 181 and 366
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Set (PPS): all subjects who correctly receive the vaccine doses, provided immunogenicity data at the relevant time points and were not excluded due to reasons defined prior to the analysis. This outcome measure is applicable only for 4-sites, 1-week with HRIG and 2-sites, TRC with HRIG Groups
Arm/Group Title 4-sites, 1-week WITH HRIG 2-sites, TRC WITH HRIG
Hide Arm/Group Description:
12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) to adults only, according to the “4-sites, 1-week” regimen HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight
8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the “2-sites, TRC”, updated Thai Red Cross regimen, with or without HRIG administered on day 1
Overall Number of Participants Analyzed 66 72
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of Subjects
Day 1 (N= 66, 72)
0
(0 to 5)
0
(0 to 5)
Day 8 (N= 66, 72)
8
(3 to 17)
10
(4 to 19)
Day 15 (N= 65, 72)
100
(94 to 100)
99
(93 to 100)
Day 50 (N= 65, 69)
95
(87 to 99)
100
(95 to 100)
Day 91 (N= 65, 72)
83
(72 to 91)
99
(93 to 100)
Day 181 (N= 65, 71)
77
(65 to 86)
85
(74 to 92)
Day 366 (N= 65, 69)
66
(53 to 77)
70
(57 to 80)
Time Frame Day 1 to day 366 (Study Groups: A1- 4-sites, 1-week” (4-4-4-0-0) ID PEP regimen without HRIG, A2- 4-sites, 1-week” (4-4-4-0-0) ID PEP regimen with HRIG, B1- 2-sites TRC” (2-2-2-0-2) ID PEP regimen without HRIG, B2- 2-sites TRC” (2-2-2-0-2) ID PEP regimen with HRIG).
Adverse Event Reporting Description Solicited local,systemic AEs & associated medications will be recorded on diary cards for 3,4, 7 & 7 days post vaccination on Visits 1,2,3 & 5,respectively.Unsolicited AEs & associated vaccinations will be collected in diary cards from D1-29 for Groups A1 & A2 & from D1-50 for Groups B1 & B2.After D29/50, until D366 only SAEs & AEs leading to withdrawal & associated vaccinations will be recorded.Number of exposed set participants analyzed for safety is different from the PPS for immunogenicity.
 
Arm/Group Title 4-sites, 1-week WITHOUT HRIG 4-sites, 1-week WITH HRIG 2-sites, TRC WITHOUT HRIG 2-sites, TRC WITH HRIG
Hide Arm/Group Description 12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) according to the “4-sites, 1-week” regimen 12 doses of the PCEC rabies vaccine, administered ID (0.1mL for each injection) to adults only, according to the “4-sites, 1-week” regimen HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight 8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) according to the “2-sites, TRC”, updated Thai Red Cross regimen. 8 doses of the PCEC rabies vaccine, administered ID (0.1ml for each injection) to adults only, according to the “2-sites, TRC”, updated Thai Red Cross regimen. HRIG administered on day 1 (before the first dose of the vaccine) in a dose of 20 IU/kg body weight intramuscularly
All-Cause Mortality
4-sites, 1-week WITHOUT HRIG 4-sites, 1-week WITH HRIG 2-sites, TRC WITHOUT HRIG 2-sites, TRC WITH HRIG
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
4-sites, 1-week WITHOUT HRIG 4-sites, 1-week WITH HRIG 2-sites, TRC WITHOUT HRIG 2-sites, TRC WITH HRIG
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/356 (1.40%)   1/85 (1.18%)   4/353 (1.13%)   2/89 (2.25%) 
Blood and lymphatic system disorders         
Anaemia * 1  1/356 (0.28%)  0/85 (0.00%)  0/353 (0.00%)  0/89 (0.00%) 
Cardiac disorders         
Angina Unstable * 1  0/356 (0.00%)  0/85 (0.00%)  0/353 (0.00%)  1/89 (1.12%) 
Gastrointestinal disorders         
Gastritis * 1  1/356 (0.28%)  0/85 (0.00%)  0/353 (0.00%)  0/89 (0.00%) 
Irritable Bowel Syndrome * 1  0/356 (0.00%)  0/85 (0.00%)  1/353 (0.28%)  0/89 (0.00%) 
General disorders         
Pyrexia * 1  1/356 (0.28%)  0/85 (0.00%)  0/353 (0.00%)  0/89 (0.00%) 
Immune system disorders         
Influenza * 1  1/356 (0.28%)  0/85 (0.00%)  0/353 (0.00%)  0/89 (0.00%) 
Infections and infestations         
Appendiceal Abscess * 1  0/356 (0.00%)  1/85 (1.18%)  0/353 (0.00%)  0/89 (0.00%) 
Appendicitis Perforated * 1  1/356 (0.28%)  0/85 (0.00%)  0/353 (0.00%)  0/89 (0.00%) 
Dengue Fever * 1  1/356 (0.28%)  1/85 (1.18%)  1/353 (0.28%)  0/89 (0.00%) 
Gastroenteritis * 1  0/356 (0.00%)  0/85 (0.00%)  1/353 (0.28%)  0/89 (0.00%) 
HIV Infection * 1  1/356 (0.28%)  0/85 (0.00%)  0/353 (0.00%)  0/89 (0.00%) 
Hand-Foot-And-Mouth Disease * 1  0/356 (0.00%)  0/85 (0.00%)  1/353 (0.28%)  0/89 (0.00%) 
Pneumonia * 1  0/356 (0.00%)  0/85 (0.00%)  1/353 (0.28%)  0/89 (0.00%) 
Pseudomonal Sepsis * 1  0/356 (0.00%)  0/85 (0.00%)  1/353 (0.28%)  0/89 (0.00%) 
Tonsillitis * 1  0/356 (0.00%)  1/85 (1.18%)  1/353 (0.28%)  0/89 (0.00%) 
Urinary Tract Infection * 1  0/356 (0.00%)  0/85 (0.00%)  0/353 (0.00%)  1/89 (1.12%) 
Injury, poisoning and procedural complications         
Animal Bite * 1  5/356 (1.40%)  0/85 (0.00%)  4/353 (1.13%)  2/89 (2.25%) 
Animal Scratch * 1  1/356 (0.28%)  0/85 (0.00%)  2/353 (0.57%)  1/89 (1.12%) 
Joint Dislocation * 1  0/356 (0.00%)  0/85 (0.00%)  1/353 (0.28%)  0/89 (0.00%) 
Road Traffic Accident * 1  0/356 (0.00%)  0/85 (0.00%)  1/353 (0.28%)  0/89 (0.00%) 
Reproductive system and breast disorders         
Dysfunctional Uterine Bleeding * 1  1/356 (0.28%)  0/85 (0.00%)  0/353 (0.00%)  0/89 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Pneumothorax * 1  0/356 (0.00%)  0/85 (0.00%)  1/353 (0.28%)  0/89 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
4-sites, 1-week WITHOUT HRIG 4-sites, 1-week WITH HRIG 2-sites, TRC WITHOUT HRIG 2-sites, TRC WITH HRIG
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   292/356 (82.02%)   78/85 (91.76%)   298/353 (84.42%)   82/89 (92.13%) 
Gastrointestinal disorders         
DIARRHOEA  1  28/356 (7.87%)  8/85 (9.41%)  20/353 (5.67%)  8/89 (8.99%) 
NAUSEA  1  22/356 (6.18%)  4/85 (4.71%)  12/353 (3.40%)  7/89 (7.87%) 
VOMITING  1  15/356 (4.21%)  1/85 (1.18%)  20/353 (5.67%)  4/89 (4.49%) 
General disorders         
CHILLS  1  15/356 (4.21%)  4/85 (4.71%)  13/353 (3.68%)  5/89 (5.62%) 
FATIGUE  1  53/356 (14.89%)  16/85 (18.82%)  52/353 (14.73%)  24/89 (26.97%) 
INJECTION SITE ERYTHEMA  1  195/356 (54.78%)  59/85 (69.41%)  168/353 (47.59%)  56/89 (62.92%) 
INJECTION SITE INDURATION  1  52/356 (14.61%)  13/85 (15.29%)  62/353 (17.56%)  13/89 (14.61%) 
INJECTION SITE PAIN  1  77/356 (21.63%)  18/85 (21.18%)  89/353 (25.21%)  20/89 (22.47%) 
INJECTION SITE SWELLING  1  39/356 (10.96%)  8/85 (9.41%)  47/353 (13.31%)  4/89 (4.49%) 
PYREXIA  1  15/356 (4.21%)  3/85 (3.53%)  27/353 (7.65%)  4/89 (4.49%) 
VACCINATION SITE ERYTHEMA  1  82/356 (23.03%)  19/85 (22.35%)  79/353 (22.38%)  23/89 (25.84%) 
VACCINATION SITE INDURATION  1  26/356 (7.30%)  5/85 (5.88%)  22/353 (6.23%)  7/89 (7.87%) 
VACCINATION SITE SWELLING  1  13/356 (3.65%)  5/85 (5.88%)  19/353 (5.38%)  2/89 (2.25%) 
Infections and infestations         
NASOPHARYNGITIS  1  13/356 (3.65%)  1/85 (1.18%)  28/353 (7.93%)  2/89 (2.25%) 
UPPER RESPIRATORY TRACT INFECTION  1  19/356 (5.34%)  6/85 (7.06%)  28/353 (7.93%)  5/89 (5.62%) 
Metabolism and nutrition disorders         
DECREASED APPETITE  1  19/356 (5.34%)  5/85 (5.88%)  12/353 (3.40%)  7/89 (7.87%) 
Musculoskeletal and connective tissue disorders         
ARTHRALGIA  1  33/356 (9.27%)  9/85 (10.59%)  33/353 (9.35%)  17/89 (19.10%) 
MYALGIA  1  45/356 (12.64%)  19/85 (22.35%)  41/353 (11.61%)  19/89 (21.35%) 
Nervous system disorders         
HEADACHE  1  53/356 (14.89%)  21/85 (24.71%)  54/353 (15.30%)  31/89 (34.83%) 
Skin and subcutaneous tissue disorders         
RASH  1  21/356 (5.90%)  7/85 (8.24%)  24/353 (6.80%)  6/89 (6.74%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (17.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis’ agreement with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publications of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Name/Title: Posting Director
Organization: Novartis Vaccines
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT02177032     History of Changes
Other Study ID Numbers: V49_30
2013-CT0191 ( Registry Identifier: registry.healthresearch.ph )
First Submitted: June 24, 2014
First Posted: June 27, 2014
Results First Submitted: August 18, 2016
Results First Posted: April 7, 2017
Last Update Posted: April 7, 2017