Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase 3b, Randomized, Open-Label Study to Evaluate the Safety and Immunogenicity of Select Travel Vaccines When Administered Concomitantly With MenACWY in Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01466387
Recruitment Status : Completed
First Posted : November 8, 2011
Results First Posted : March 11, 2014
Last Update Posted : March 11, 2014
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
Conditions Meningococcal Disease
Meningococcal Meningitis
Typhoid
Yellow Fever
Rabies
Japanese Encephalitis
Interventions Biological: Typhoid Vi Polysaccharide Vaccine
Biological: Yellow Fever Vaccine
Biological: Japanese Encephalitis Vaccine
Biological: Rabies Vaccine
Biological: MenACWY-CRM Vaccine
Enrollment 552
Recruitment Details Subjects were enrolled at 5 sites (Berhard Nocht Institut, Germany, Berliner Centrum fuer Reise, Germany, Universitat Rostock, Germany, University of Munich, Germany, Vacc and Travel Med. Center, Czech Republic)
Pre-assignment Details All enrolled subjects were included in the trial.
Arm/Group Title TF+YF TF+YF+MenACWY-CRM197 JE+Rabies JE+Rabies+MenACWY-CRM197 Rabies MenACWY-CRM197 (Combined)
Hide Arm/Group Description Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide and yellow fever vaccine. Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide, yellow fever and meningococcal ACWY conjugate vaccine. Subjects ≥18 years to ≤60 years of age who received two doses of Japanese encephalitis and three doses of Rabies vaccine. Subjects ≥18 years to ≤60 years of age who received two doses of Japanese encephalitis and three doses of Rabies and one dose of meningococcal ACWY conjugate vaccine. Subjects ≥18 years to ≤60 years of age who received three doses of Rabies vaccine. Subjects ≥18 years to ≤60 years of age who received one dose of meningococcal ACWY conjugate vaccine.
Period Title: Overall Study
Started 101 100 99 101 51 100
Completed 100 100 98 99 51 99
Not Completed 1 0 1 2 0 1
Reason Not Completed
Adverse Event             0             0             1             1             0             0
Lost to Follow-up             0             0             0             0             0             1
Protocol Violation             1             0             0             1             0             0
Arm/Group Title TF+YF TF+YF+MenACWY-CRM197 JE+Rabies JE+Rabies+MenACWY-CRM197 Rabies MenACWY-CRM197 (Combined) Total
Hide Arm/Group Description Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide and yellow fever vaccine. Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide, yellow fever and meningococcal ACWY conjugate vaccine. Subjects ≥18 years to ≤60 years of age who received two doses of Japanese encephalitis and three doses of Rabies vaccine. Subjects ≥18 years to ≤60 years of age who received two doses of Japanese encephalitis and three doses of Rabies and one dose of meningococcal ACWY conjugate vaccine. Subjects ≥18 years to ≤60 years of age who received three doses of Rabies vaccine. Subjects ≥18 years to ≤60 years of age who received one dose of meningococcal ACWY conjugate vaccine. Total of all reporting groups
Overall Number of Baseline Participants 101 100 99 101 51 100 552
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 101 participants 100 participants 99 participants 101 participants 51 participants 100 participants 552 participants
36.5  (10.8) 35.1  (11.0) 35.0  (11.5) 35.0  (11.1) 35.8  (11.6) 36.9  (11.2) 35.7  (11.2)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 100 participants 99 participants 101 participants 51 participants 100 participants 552 participants
Female
49
  48.5%
44
  44.0%
53
  53.5%
50
  49.5%
21
  41.2%
50
  50.0%
267
  48.4%
Male
52
  51.5%
56
  56.0%
46
  46.5%
51
  50.5%
30
  58.8%
50
  50.0%
285
  51.6%
1.Primary Outcome
Title Geometric Mean Anti-typhoid Vi Antibody Concentrations
Hide Description Assessment was made to demonstrate the non-inferiority of the geometric mean anti-typhoid Vi antibody concentrations, 28 days after the vaccination of typhoid Vi polysaccharide (TF) and yellow fever (YF) vaccines given concomitantly with MenACWY-CRM197 to typhoid Vi polysaccharide and yellow fever vaccines given alone in healthy adults aged ≥18 years to ≤60 years.
Time Frame Baseline and 1 month postvaccination (day 29).
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the per-protocol (PP) set, ie, the subjects who received the vaccine correctly; provided evaluable serum samples at the relevant time points; and had no major protocol violations as defined prior to analysis.
Arm/Group Title TF+YF TF+YF+MenACWY-CRM197
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide and yellow fever vaccine.
Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide, yellow fever and meningococcal ACWY conjugate vaccine.
Overall Number of Participants Analyzed 100 99
Geometric Mean (95% Confidence Interval)
Unit of Measure: El.U/mL
Day 1 (Typhoid Fever)
6.37
(5.3 to 7.65)
5.6
(4.66 to 6.73)
Day 29 (Typhoid Fever)
134
(104 to 174)
153
(118 to 197)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TF+YF, TF+YF+MenACWY-CRM197
Comments The primary criterion for immunogenicity (postvaccination, day 29) was that the lower limit of the two-sided 95% confidence interval around the observed ratio of geometric mean concentrations between one dose of typhoid Vi polysaccharide and yellow fever vaccines given concomitantly with MenACWY-CRM197 to typhoid Vi polysaccharide and yellow fever vaccines given alone was greater than 0.5.
Type of Statistical Test Non-Inferiority or Equivalence
Comments GMC TF+YF+MenACWY-CRM/GMC TF+YF.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments The testing was done by assessing the confidence interval of the ratio.
Method ANCOVA
Comments The ANCOVA model included vaccine group and center as factors, age as covariate and was adjusted for baseline.
Method of Estimation Estimation Parameter Ratio of GMC
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
0.81 to 1.6
Estimation Comments [Not Specified]
2.Primary Outcome
Title Geometric Mean Anti-Yellow Fever Antibody Titer
Hide Description Assessment was made to demonstrate the non-inferiority of the geometric mean anti-yellow fever antibody titers, 28 days after the vaccination of typhoid Vi polysaccharide (TF) and yellow fever (YF) vaccines given concomitantly with MenACWY-CRM197 to typhoid Vi polysaccharide and yellow fever vaccines given alone in healthy adults aged ≥18 years to ≤60 years.
Time Frame Baseline and 1 month postvaccination (day 29).
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the per-protocol (PP) set, ie, the subjects who received the vaccine correctly; provided evaluable serum samples at the relevant time points; and had no major protocol violations as defined prior to analysis.
Arm/Group Title TF+YF TF+YF+MenACWY-CRM197
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide and yellow fever vaccine.
Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide, yellow fever and meningococcal ACWY conjugate vaccine.
Overall Number of Participants Analyzed 100 99
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Day 1 (Yellow Fever)
9.05
(6.82 to 12)
12
(8.68 to 15)
Day 29 (Yellow Fever)
5244
(3929 to 7000)
5022
(3754 to 6717)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection TF+YF, TF+YF+MenACWY-CRM197
Comments The primary criterion for immunogenicity (postvaccination, day 29) was that the lower limit of the two sided 95% CI around the observed ratio of geometric mean titers between one dose of typhoid Vi polysaccharide and yellow fever vaccines given concomitantly with MenACWY-CRM197 to typhoid Vi polysaccharide and yellow fever vaccines given alone was greater than 0.5.
Type of Statistical Test Non-Inferiority or Equivalence
Comments GMT TF+YF+MenACWY/GMT TF+YF.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments The testing was done by assessing the confidence interval of the ratio.
Method ANCOVA
Comments The ANCOVA model included vaccine group and center as factors, age as covariate and was adjusted for baseline.
Method of Estimation Estimation Parameter Ratio of GMT.
Estimated Value 0.96
Confidence Interval (2-Sided) 95%
0.65 to 1.41
Estimation Comments [Not Specified]
3.Primary Outcome
Title Geometric Mean Anti-Japanese Encephalitis Neutralizing Antibody Titers
Hide Description Assessment was made to demonstrate the non-inferiority of the geometric mean anti-Japanese encephalitis neutralizing antibody titers, 28 days after the vaccination of the second dose of Japanese Encephalitis vaccine and third dose of the rabies virus vaccine given concomitantly with MenACWY-CRM197 or alone in healthy adults aged ≥18 years to ≤60 years.
Time Frame Baseline and 1 month post last vaccination (day 57).
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the PP set, i.e. the subjects who received the vaccine correctly; provided evaluable serum samples at the relevant time points; and had no major protocol violations as defined prior to analysis.
Arm/Group Title JE+Rabies JE+Rab+MenACWY-CRM197
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies vaccine.
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies vaccine and one dose of Meningococcal conjugate vaccine.
Overall Number of Participants Analyzed 96 97
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Day 1 (Japanese Encephalitis)
5.61
(5.11 to 6.15)
5.58
(5.09 to 6.12)
Day 57 (Japanese Encephalitis)
183
(151 to 221)
165
(136 to 199)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection JE+Rabies, JE+Rab+MenACWY-CRM197
Comments The primary criterion for immunogenicity (postvaccination, day 57) was that the lower limit of the two sided 95% CI around the observed ratio of geometric mean titers between the second dose of Japanese Encephalitis and third dose of rabies virus vaccines given concomitantly with MenACWY-CRM197 to Japanese Encephalitis and rabies virus vaccines given alone was greater than 0.5.
Type of Statistical Test Non-Inferiority or Equivalence
Comments GMT JE + Rab + MenACWY-CRM/GMT JE + Rab.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments The testing was done by assessing the confidence interval of the ratio.
Method ANCOVA
Comments The ANCOVA model included vaccine group and centers as factors, age as covariate and was adjusted for baseline.
Method of Estimation Estimation Parameter Ratio of GMT
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
0.7 to 1.16
Estimation Comments [Not Specified]
4.Primary Outcome
Title Geometric Mean Anti-Rabies Virus Neutralizing Antibody Concentration
Hide Description Assessment was made to demonstrate the non-inferiority of the geometric mean anti-rabies virus neutralizing antibody concentrations, 28 days after the vaccination of the second dose of Japanese encephalitis vaccine and third dose of rabies virus vaccine given concomitantly with MenACWY-CRM197 or alone in healthy adults aged ≥18 years to ≤60 years.
Time Frame Baseline and 1 month post last vaccination (day 57).
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the per-protocol (PP) set, i.e. the subjects who received the vaccine correctly; provided evaluable serum samples at the relevant time points; and had no major protocol violations as defined prior to analysis.
Arm/Group Title JE+Rabies JE+Rab+MenACWY-CRM197
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies vaccine.
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies vaccine and one dose of Meningococcal conjugate vaccine.
Overall Number of Participants Analyzed 96 97
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/mL
Day 1 (Rabies)
0.056
(0.05 to 0.062)
0.049
(0.044 to 0.054)
Day 57 (Rabies)
12
(9.68 to 14)
11
(8.84 to 13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection JE+Rabies, JE+Rab+MenACWY-CRM197
Comments The primary criterion for immunogenicity (postvaccination, day 57) was that the lower limit of the two sided 95% CI around the observed ratio of geometric mean concentrations between the second dose of Japanese encephalitis and third dose of rabies virus vaccines given concomitantly with MenACWY-CRM197 to Japanese encephalitis and rabies virus vaccines given alone was greater than 0.5.
Type of Statistical Test Non-Inferiority or Equivalence
Comments GMC JE + Rab + MenACWY-CRM/GMC JE + Rab.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments The testing was done by assessing the confidence interval of the ratio.
Method ANCOVA
Comments The ANCOVA model included vaccine group and center as factors, age as covariate and was adjusted for baseline.
Method of Estimation Estimation Parameter Ratio of GMC
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.71 to 1.17
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percentages Of Subjects With Anti-YF Neutralizing Antibody Titers ≥ 1/10, 28 Days After The Vaccination Of Typhoid Vi Polysaccharide And Yellow Fever, Concomitantly With MenACWY-CRM197 Or Given Alone
Hide Description

Immunogenicity was assessed as the percentages of subjects who achieved seroprotection as measured by neutralization test for anti-YF neutralizing antibody titers after the vaccination of typhoid Vi polysaccharide and yellow fever, given alone or concomitantly with MenACWY-CRM197 on day 29.

Seroprotection is defined as percentages of subjects who achieved anti-YF neutralizing antibody titers ≥ 1/10 on day 29.

Time Frame Baseline and 1 month postvaccination (day 29).
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the Modified-Intention to Treat (MITT) set, i.e. the subjects who provided evaluable serum samples whose assay results are available for at least one antigen on baseline and on at least one post-baseline visit.
Arm/Group Title TF+YF TF+YF+MenACWY-CRM197
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide and yellow fever vaccine.
Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide, yellow fever and meningococcal ACWY conjugate vaccine.
Overall Number of Participants Analyzed 100 100
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 1 (Yellow Fever)
34
(25 to 44)
36
(27 to 46)
Day 29 (Yellow Fever)
100
(96 to 100)
97
(91 to 99)
6.Secondary Outcome
Title Percentages Of Subjects With Anti-JE Neutralizing Antibody Titers ≥ 1/10, 28 Days After The Vaccination Of The Last Doses Of Japanese Encephalitis And Rabies, Given Concomitantly With MenACWY-CRM197 Or Alone
Hide Description

Immunogenicity was measured as the percentages of subjects who achieved seroprotection as measured by neutralization test for anti-Japanese encephalitis neutralizing antibody titers, 28 days after administration of the second dose of Japanese encephalitis virus vaccine and 28 days after the vaccination of third dose of rabies virus vaccine, given alone or concomitantly with MenACWY-CRM197.

Seroprotection is defined as percentages of subjects who achieved anti-JE neutralizing titers ≥ 1/10 on Day 57.

Time Frame Baseline and 1 month post last vaccination (day 57).
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the MITT data set.
Arm/Group Title JE+Rabies JE+Rabies+MenACWY-CRM197
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies vaccine.
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies and one dose of meningococcal ACWY conjugate vaccine.
Overall Number of Participants Analyzed 98 99
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subects
Day 1 (Japanese Encephalitis)
3
(1 to 9)
4
(1 to 10)
Day 57 (Japanese Encephalitis)
99
(94 to 100)
98
(93 to 100)
7.Secondary Outcome
Title Percentages Of Subjects With Anti-Rabies Virus Antibody Concentrations ≥ 0.5 IU/mL 28 Days After the Vaccination Of The Last Doses Of Japanese Encephalitis And Rabies Virus, Given Concomitantly With MenACWY-CRM197 Or Alone
Hide Description

Immunogenicity was assessed as the percentages of subjects who achieved seroprotection as measured by neutralization test for anti-rabies neutralizing antibody titers, 28 days after administration of the second dose of Japanese encephalitis virus vaccine and 28 days after the vaccination of third dose of rabies virus vaccine, given alone or concomitantly with MenACWY-CRM197.

Seroprotection is defined as a subject with a baseline hSBA titer < 1:4, seroresponse was defined as a post-vaccination hSBA titer ≥ 1:8; for a subject with a baseline hSBA titer ≥ 1:4, seroresponse was defined as a post-vaccination hSBA titer of at least 4 times the baseline.

Time Frame Baseline and 1 month post last vaccination (day 57).
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the MITT data set.
Arm/Group Title JE+Rabies JE+Rabies+MenACWY-CRM197
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies vaccine.
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies vaccine and one dose of Meningococcal conjugate vaccine.
Overall Number of Participants Analyzed 98 99
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 1 (Rabies)
3
(1 to 9)
1
(0.026 to 5)
Day 57 (Rabies)
100
(96 to 100)
100
(96 to 100)
8.Secondary Outcome
Title Geometric Mean hSBA Titers For Meningococcal Serogroups A,C,W,Y 28 Days After The Vaccination Of MenACWY-CRM197 Given Concomitantly With Typhoid Vi Polysaccharide And Yellow Fever Vaccines Alone
Hide Description Immunogenicity was assessed by Serum Bactericidal Assay using human complement (hSBA) geometric mean titers (GMTs) for meningococcal serogroups A,C,W,Y 28 days after administration of MenACWY-CRM197 given concomitantly with typhoid Vi polysaccharide and yellow fever vaccines or alone.
Time Frame Baseline and 1 month postvaccination (day 29).
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the MITT data set.
Arm/Group Title MenACWY-CRM197 (Combined) TF+YF+MenACWY-CRM197
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received one dose of meningococcal ACWY conjugate vaccine.
Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide, yellow fever and meningococcal ACWY conjugate vaccine.
Overall Number of Participants Analyzed 99 100
Geometric Mean (95% Confidence Interval)
Unit of Measure: titers
Serogroup A (Day 1)
2.94
(2.43 to 3.56)
2.78
(2.3 to 3.36)
Serogroup A (Day 29)
65
(44 to 95)
62
(42 to 90)
Serogroup C (Day 1)
7.94
(5.94 to 11)
7.03
(5.27 to 9.38)
Serogroup C (Day 29)
49
(35 to 70)
54
(38 to 76)
Serogroup W (Day 1)
50
(35 to 71)
32
(22 to 45)
Serogroup W (Day 29)
129
(94 to 177)
211
(154 to 290)
Serogroup Y (Day 1)
7.61
(5.71 to 10)
7.76
(5.83 to 10)
Serogroup Y (Day 29)
89
(62 to 129)
78
(54 to 113)
9.Secondary Outcome
Title Seroresponse Rate For Meningococcal Serogroups A,C,W,Y 28 Days After Vaccination of MenACWY-CRM197 Given Concomitantly With Typhoid Vi Polysaccharide and Yellow Fever Vaccines or Alone
Hide Description

Immunogenicity was assessed by seroresponse rates as measured by human serum bactericidal activity (hSBA) titers for meningococcal serogroups A,C,W,Y 28 days after administration of MenACWY-CRM197 given concomitantly with typhoid Vi polysaccharide and yellow fever vaccines or alone.

Seroresponse is defined as a postvaccination hSBA titer ≥1:8; for a subject with a baseline hSBA titer ≥1:4, seroresponse is defined as a postvaccination hSBA titer of at least four times the baseline.

Time Frame 1 month postvaccination (day 29)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the MITT data set.
Arm/Group Title TF + YF + MenACWY-CRM197 MenACWY-CRM197 (Combined)
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide, yellow fever and meningococcal ACWY conjugate vaccine.
Subjects ≥18 years to ≤60 years of age who received one dose of meningococcal ACWY conjugate vaccine.
Overall Number of Participants Analyzed 100 99
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Serogroup A (Overall Seroresponse)
72
(62 to 81)
71
(61 to 79)
Serogroup C (Overall Seroresponse)
48
(38 to 58)
47
(37 to 58)
Serogroup W (Overall Seroresponse)
51
(40 to 61)
30
(21 to 40)
Serogroup Y (Overall Seroresponse)
63
(53 to 72)
66
(55 to 75)
10.Secondary Outcome
Title Geometric Mean hSBA Titers for Meningococcal Serogroups A,C,W,Y 28 Days After the Vaccination of MenACWY-CRM197 Given Concomitantly With Japanese Encephalitis and Rabies Virus Vaccines or Alone
Hide Description Immunogenicity was measured by human serum bactericidal activity (hSBA) geometric mean titers (GMTs) for meningococcal serogroups A,C,W,Y 28 days after administration of MenACWY-CRM197 given concomitantly with Japanese encephalitis and rabies virus vaccines or alone.
Time Frame Baseline and 1 month post last vaccination (day 29 or day 57).
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the MITT data set.
Arm/Group Title JE + Rab + MenACWY-CRM197 MenACWY-CRM197 (Combined)
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies and one dose of meningococcal ACWY conjugate vaccine.
Subjects ≥18 years to ≤60 years of age who received one dose of meningococcal ACWY conjugate vaccine.
Overall Number of Participants Analyzed 99 99
Geometric Mean (95% Confidence Interval)
Unit of Measure: titers
Serogroup A (Day 1)
3.21
(2.65 to 3.88)
2.94
(2.43 to 3.56)
Serogroup A (Day 29 or Day 57)
32
(22 to 47)
65
(44 to 95)
Serogroup C (Day 1)
8.81
(6.59 to 12)
7.94
(5.94 to 11)
Serogroup C (Day 29 or Day 57)
44
(31 to 62)
49
(35 to 70)
Serogroup W (Day 1)
54
(38 to 77)
50
(35 to 71)
Serogroup W (Day 29 or Day 57)
119
(87 to 164)
129
(94 to 177)
Serogroup Y (Day 1)
8.11
(6.08 to 11)
7.61
(5.71 to 10)
Serogroup Y (Day 29 or Day 57)
55
(38 to 80)
89
(62 to 129)
11.Secondary Outcome
Title Seroresponse Rate for Meningococcal Serogroups A,C,W,Y 28 Days After Vaccination of MenACWY-CRM197 Given Concomitantly With Japanese Encephalitis and Rabies Virus Vaccines or Alone
Hide Description

Immunogenicity was assessed by seroresponse rates as measured by human serum bactericidal activity (hSBA) titers for meningococcal serogroups A,C,W,Y 28 days after administration of MenACWY-CRM197 given concomitantly with Japanese encephalitis and rabies virus vaccines or alone.

Seroresponse is defined as a subject with a baseline hSBA titer < 1:4, seroresponse was defined as a post-vaccination hSBA titer ≥ 1:8; for a subject with a baseline hSBA titer ≥ 1:4, seroresponse was defined as a postvaccination hSBA titer of at least 4 times the baseline.

Time Frame 1 month post last vaccination (day 29 or day 57)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the MITT data set.
Arm/Group Title JE + Rab + MenACWY-CRM197 MenACWY-CRM197 (Combined)
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies and one dose of meningococcal ACWY conjugate vaccine.
Subjects ≥18 years to ≤60 years of age who received one dose of meningococcal ACWY conjugate vaccine.
Overall Number of Participants Analyzed 99 99
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Serogroup A (Overall Seroresponse)
60
(49 to 69)
71
(61 to 79)
Serogroup C (Overall Seroresponse)
43
(33 to 54)
47
(37 to 58)
Serogroup W (Overall Seroresponse)
32
(23 to 42)
30
(21 to 40)
Serogroup Y (Overall Seroresponse)
56
(45 to 66)
66
(55 to 75)
12.Secondary Outcome
Title Geometric Mean Rabies Virus Neutralizing Antibody Concentration 28 Days After the Last Vaccination Of Rabies Virus Vaccine Concomitantly Either With Japanese Encephalitis or With Japanese Encephalitis And MenACWY-CRM197
Hide Description The immunogenicity was assessed in rabies virus vaccine as measured by geometric mean rabies virus neutralizing antibody concentration, 28 days after vaccination of the third dose, when administered alone or concomitantly either with Japanese encephalitis vaccine or with Japanese Encephalitis and MenACWY-CRM197 vaccines.
Time Frame Baseline and 1 month post last vaccination (day 57).
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the MITT data set.
Arm/Group Title JE + Rabies + MenACWY-CRM197 JE + Rabies Rabies
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies and one dose of meningococcal ACWY conjugate vaccine.
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of rabies vaccine.
Subjects ≥18 years to ≤60 years of age who received three doses of Rabies vaccine
Overall Number of Participants Analyzed 99 98 51
Geometric Mean (95% Confidence Interval)
Unit of Measure: IU/mL
Day 1 (Rabies)
0.051
(0.044 to 0.059)
0.057
(0.049 to 0.065)
0.068
(0.056 to 0.082)
Day 57 (Rabies)
11
(8.84 to 13)
11
(9.49 to 14)
8.97
(6.98 to 12)
13.Secondary Outcome
Title Percentages of Subjects With Anti-rabies Virus Concentrations ≥ 0.5 IU/mL, 28 Days After the Last Vaccination of Rabies Virus Vaccine Concomitantly Either With Japanese Encephalitis or With Japanese Encephalitis and MenACWY-CRM197
Hide Description

Immunogenicity was measured as the percentages of subjects who achieved seroprotection of anti-rabies virus antibody concentrations 28 days after vaccination of the third dose of rabies virus vaccine, when administered alone or concomitantly either with Japanese encephalitis or with Japanese encephalitis and MenACWY-CRM197 vaccines.

Seroprotection is defined as percentages of subjects who achieved anti-rabies virus antibody concentrations ≥ 0.5 IU/mL on day 57.

Time Frame Baseline and 1 month post last vaccination (day 57).
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was done on the MITT data set.
Arm/Group Title JE + Rabies + MenACWY-CRM197 JE + Rabies Rabies
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies and one dose of meningococcal ACWY conjugate vaccine.
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies vaccine.
Subjects ≥18 years to ≤60 yars of age who received three doses of Rabies vaccine.
Overall Number of Participants Analyzed 99 98 51
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
Day 1 (Rabies)
1
(0.026 to 5)
3
(1 to 9)
8
(2 to 19)
Day 57 (Rabies)
100
(96 to 100)
100
(96 to 100)
100
(93 to 100)
14.Secondary Outcome
Title Number of Subjects With Adverse Events of Special Interest After Any Vaccination of Japanese Encephalitis and Rabies Virus Vaccines Given Concomitantly With MenACWY-CRM197 or Alone
Hide Description In addition to the AEs and SAEs. Additional AESI were collected from day 1 to day 57 postvaccination in subjects after the vaccination of Japanese encephalitis and rabies virus vaccines given concomitantly with MenACWY-CRM197 or alone.
Time Frame day 1 to day 57 post last vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on the safety data set, i.e. the subjects in the exposed population who provided postvaccination safety data.
Arm/Group Title JE + Rabies + MenACWY-CRM197 JE + Rabies
Hide Arm/Group Description:
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies and one dose of meningococcal ACWY conjugate vaccine.
Subjects ≥18 years to ≤60 years of age who received two doses of Japanese Encephalitis and three doses of Rabies vaccine.
Overall Number of Participants Analyzed 101 99
Measure Type: Number
Unit of Measure: subjects
Injection site erythema 0 1
Hypersensitivity 1 0
Paresthesia 0 1
Erythema 1 0
Pruritus 1 1
Hot flush 1 0
Time Frame day 1 to day 29 (one month postvaccination); day 1 to day 57 (one month post last vaccination)
Adverse Event Reporting Description AEs and SAEs were collected from day 1-29 for subjects vaccinated with typhoid Vi polysaccharide+YF +MenACWY-CRM197 or alone, from day 1-57 vaccinated with JE+rabies virus+MenACWY-CRM197 or alone and who received rabies vaccine alone.
 
Arm/Group Title TF+YF TF+YF+MenACWY-CRM197 JE+Rabies JE+Rabies+MenACWY-CRM197 Rabies MenACWY-CRM197 (Combined)
Hide Arm/Group Description Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide and yellow fever vaccine. Subjects ≥18 years to ≤60 years of age who received one dose of typhoid Vi polysaccharide, yellow fever and meningococcal ACWY conjugate vaccine. Subjects ≥18 years to ≤60 years of age who received two doses of Japanese encephalitis and three doses of Rabies vaccine. Subjects ≥18 years to ≤60 years of age who received two doses of Japanese encephalitis and three doses of Rabies and one dose of meningococcal ACWY conjugate vaccine. Subjects ≥18 years to ≤60 years of age who received three doses of Rabies vaccine. Subjects ≥18 years to ≤60 years of age who received one dose of meningococcal ACWY conjugate vaccine.
All-Cause Mortality
TF+YF TF+YF+MenACWY-CRM197 JE+Rabies JE+Rabies+MenACWY-CRM197 Rabies MenACWY-CRM197 (Combined)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
TF+YF TF+YF+MenACWY-CRM197 JE+Rabies JE+Rabies+MenACWY-CRM197 Rabies MenACWY-CRM197 (Combined)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/101 (0.00%)   0/100 (0.00%)   1/99 (1.01%)   1/101 (0.99%)   0/51 (0.00%)   0/100 (0.00%) 
Injury, poisoning and procedural complications             
Injury * 1  0/101 (0.00%)  0/100 (0.00%)  1/99 (1.01%)  0/101 (0.00%)  0/51 (0.00%)  0/100 (0.00%) 
Musculoskeletal and connective tissue disorders             
Intervertebral disc protrusion * 1  0/101 (0.00%)  0/100 (0.00%)  0/99 (0.00%)  1/101 (0.99%)  0/51 (0.00%)  0/100 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TF+YF TF+YF+MenACWY-CRM197 JE+Rabies JE+Rabies+MenACWY-CRM197 Rabies MenACWY-CRM197 (Combined)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   27/101 (26.73%)   30/100 (30.00%)   23/99 (23.23%)   22/101 (21.78%)   9/51 (17.65%)   9/100 (9.00%) 
General disorders             
Injection site pain * 1  12/101 (11.88%)  8/100 (8.00%)  6/99 (6.06%)  4/101 (3.96%)  2/51 (3.92%)  2/100 (2.00%) 
Headache * 1  7/101 (6.93%)  10/100 (10.00%)  9/99 (9.09%)  5/101 (4.95%)  5/51 (9.80%)  4/100 (4.00%) 
Influenza like illness * 1  5/101 (4.95%)  9/100 (9.00%)  5/99 (5.05%)  6/101 (5.94%)  0/51 (0.00%)  2/100 (2.00%) 
Infections and infestations             
Nasopharyngitis * 1  3/101 (2.97%)  3/100 (3.00%)  3/99 (3.03%)  7/101 (6.93%)  2/51 (3.92%)  1/100 (1.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT 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.
Results Point of Contact
Name/Title: Posting Director
Organization: Novartis Vaccines and Diagnostics
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT01466387     History of Changes
Other Study ID Numbers: V59_38
2011-000475-14 ( EudraCT Number )
First Submitted: November 3, 2011
First Posted: November 8, 2011
Results First Submitted: August 21, 2013
Results First Posted: March 11, 2014
Last Update Posted: March 11, 2014