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Study of Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) in Children Previously Immunized With JE-CV

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ClinicalTrials.gov Identifier: NCT01190228
Recruitment Status : Completed
First Posted : August 27, 2010
Results First Posted : November 8, 2017
Last Update Posted : November 8, 2017
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Japanese Encephalitis
Varicella
Interventions Biological: JE-CV Vaccine
Biological: Varicella Vaccine
Enrollment 454
Recruitment Details Study participants were enrolled from 25 August 2010 to 12 October 2015 at 3 clinic sites in the Philippines.
Pre-assignment Details A total of 454 participants who met all inclusion criteria and no exclusion criteria were enrolled in Group 1 or randomized to Group 2 or Group 3 on Day 0. All except 4 participants in Group 1 were vaccinated as planned (345 participants in Group 1, 46 participants in Group 2, and 59 participants in Group 3).
Arm/Group Title JE-CV Vaccine Booster JE-CV Vaccine First Dose Varicella Vaccine Group
Hide Arm/Group Description Participants previously received a single dose of JE-CV in the JEC02 trial and also received a booster dose of JE-CV in the current trial. JE vaccine naïve control participants received a single dose of JE-CV on Day 0 (Immunogenicity Control group). JE vaccine naïve control participants received a varicella vaccination (Okavax®) on Day 0 (Safety Control group).
Period Title: Overall Study
Started 349 46 59
Completed 344 46 59
Not Completed 5 0 0
Reason Not Completed
Protocol Violation             4             0             0
Withdrawal by Subject             1             0             0
Arm/Group Title JE-CV Vaccine Booster JE-CV Vaccine First Dose Varicella Vaccine Group Total
Hide Arm/Group Description Participants previously received a single dose of JE-CV in the JEC02 trial and also received a booster dose of JE-CV in the current trial. JE vaccine naïve control participants received a single dose of JE-CV on Day 0 (Immunogenicity Control group). JE vaccine naïve control participants received a varicella vaccination (Okavax®) on Day 0 (Safety Control group). Total of all reporting groups
Overall Number of Baseline Participants 345 46 59 450
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 46 participants 59 participants 450 participants
<=18 years
345
 100.0%
46
 100.0%
59
 100.0%
450
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 345 participants 46 participants 59 participants 450 participants
39.6  (1.71) 39.3  (1.99) 39.3  (2.09) 39.5  (1.79)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 345 participants 46 participants 59 participants 450 participants
Female
172
  49.9%
25
  54.3%
29
  49.2%
226
  50.2%
Male
173
  50.1%
21
  45.7%
30
  50.8%
224
  49.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Philippines Number Analyzed 345 participants 46 participants 59 participants 450 participants
345 46 59 450
1.Primary Outcome
Title Percentage of Participants With JE Seroprotection Before and Following a Dose of Live Attenuated JE-CV
Hide Description The presence of JE virus neutralizing antibodies was measured using a 50% plaque reduction neutralization test (PRNT50). Seroprotection status for antibody levels against JE virus before (on Day 0) and after JE-CV vaccination (Day 7 and Day 28) was defined as neutralizing antibody titer ≥ 10 (1/dilution).
Time Frame Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Seroprotection against JE-CV vaccine was assessed in the Per Protocol Analysis Set. Data for Varicella Vaccine Group were not analyzed for this outcome measure as pre-specified in the study protocol.
Arm/Group Title JE-CV Booster JE-CV First Dose
Hide Arm/Group Description:
Participants previously received a single dose of JE-CV in the JEC02 trial and also received a booster dose of JE-CV in the current trial.
JE naïve control participants received a single dose of JE-CV on Day 0 (Immunogenicity Control group).
Overall Number of Participants Analyzed 340 39
Measure Type: Number
Unit of Measure: Percentage of participants
Day 0 (pre-vaccination) 80.3 0
Day 7 post-vaccination 96.2 15.4
Day 28 post-vaccination 100.0 89.7
2.Primary Outcome
Title Percentage of Participants With JE Seroconversion Following a Dose of Live Attenuated JE-CV Vaccine
Hide Description The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay. Seroconversion was defined as participants with a pre-vaccination titer <10 (1/dilution) and post-vaccination titer ≥10 (1/dilution, or participants with pre vaccination titer ≥10 (1/dilution) and a ≥4-fold increase from pre- to post-vaccination.
Time Frame Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Seroconversion was assessed in the Per Protocol Analysis Set. Data for Varicella Vaccine Group were not analyzed for this outcome measure as pre-specified in the study protocol.
Arm/Group Title JE-CV Booster JE-CV First Dose
Hide Arm/Group Description:
Participants previously received a single dose of JE-CV in the JEC02 trial and also received a booster dose of JE-CV in the current trial.
JE naïve control participants received a single dose of JE-CV on Day 0 (Immunogenicity Control group).
Overall Number of Participants Analyzed 340 39
Measure Type: Number
Unit of Measure: Percentage of participants
Day 7 post-vaccination 66.8 15.4
Day 28 post-vaccination 95.3 89.7
3.Primary Outcome
Title Summary of Geometric Mean Titers of JE Virus Antibodies Following a Dose of Live Attenuated JE-CV
Hide Description The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Time Frame Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Geometric mean titers of JE virus antibodies were assessed in the Per Protocol Analysis Set. Data for Varicella Vaccine Group were not analyzed for this outcome measure as pre-specified in the study protocol.
Arm/Group Title JE-CV Booster JE-CV First Dose
Hide Arm/Group Description:
Participants previously received a single dose of JE-CV in the JEC02 trial and also received a booster dose of JE-CV in the current trial.
JE naïve control participants received a single dose of JE-CV on Day 0 (Immunogenicity Control group).
Overall Number of Participants Analyzed 340 39
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers (1/dilution)
Day 0 (pre-vaccination)
39.4
(33.7 to 46.0)
5.00
(5.00 to 5.00)
Day 7 post-vaccination
231
(191 to 279)
6.41
(5.11 to 8.05)
Day 28 post-vaccination
2242
(1913 to 2628)
178
(99.7 to 318)
4.Primary Outcome
Title Summary of Geometric Mean Titer Ratios of JE Virus Antibodies Following a Dose of Live Attenuated JE-CV
Hide Description The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Time Frame Day 0 (pre-vaccination) and Day 7 and Day 28 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Geometric mean titer ratios of JE virus antibodies were assessed in the Per Protocol Analysis Set. Data for Varicella Vaccine Group were not analyzed for this outcome measure as pre-specified in the study protocol.
Arm/Group Title JE-CV Booster JE-CV First Dose
Hide Arm/Group Description:
Participants previously received a single dose of JE-CV Vaccine in the JEC02 trial and also received a booster dose of JE-CV in the current trial.
JE naïve control participants received a single dose of JE-CV on Day 0 (Immunogenicity Control group).
Overall Number of Participants Analyzed 340 39
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titer ratios (1/dilution)
Day 7 post-vaccination
5.87
(5.06 to 6.80)
1.28
(1.02 to 1.61)
Day 28 post-vaccination
57.0
(47.8 to 67.9)
35.6
(19.9 to 63.6)
5.Primary Outcome
Title Summary of Serological Flavivirus Status at Baseline of Participants Vaccinated With a Dose of Live Attenuated JE-CV
Hide Description The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay. Flavivirus positive was defined as titers against JE virus ≥10 (1/dilution) or titers against at least 1 dengue serotype ≥10 (1/dilution). Flavivirus negative was defined as titers against JE virus <10 (1/dilution) and titers against the 4 dengue serotypes <10 (1/dilution).
Time Frame Day 0 (pre-vaccination)
Hide Outcome Measure Data
Hide Analysis Population Description
Serological flavivirus status at baseline was assessed in the Full Analysis Set. Data for Varicella Vaccine Group were not analyzed for this outcome measure as pre-specified in the study protocol.
Arm/Group Title JE-CV Booster JE-CV First Dose
Hide Arm/Group Description:
Participants previously received a single dose of JE-CV in the JEC02 trial and also received a booster dose of JE-CV in the current trial.
JE naïve control participants received a single dose of JE-CV on Day 0 (Immunogenicity Control group).
Overall Number of Participants Analyzed 345 46
Measure Type: Number
Unit of Measure: Number of participants
Any JE-CV and/or dengue virus; Flavivirus positive 289 14
Any JE-CV and/or dengue virus; Flavivirus negative 56 32
JE-CV virus strain 277 7
Any dengue serotype 121 11
Dengue serotype 1 116 11
Dengue serotype 2 102 11
Dengue serotype 3 96 9
Dengue serotype 4 108 9
6.Primary Outcome
Title Percentage of Participants With JE Seroprotection Before and Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV
Hide Description The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay. Seroprotection status for antibody levels against JE virus before (on Day 0) and after JE-CV vaccination (Days 7 and 28 and Years 1, 2, 3, 4, and 5) was defined as neutralizing antibody titer ≥ 10 (1/dilution).
Time Frame Day 0 (pre-vaccination) and Days 7 and 28, and Year 1, 2, 3, 4, and 5 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Seroprotection was assessed in the Full Analysis Set. Data for JE-CV Vaccine First Dose and Varicella Vaccine Groups were not analyzed for this outcome measure as pre-specified in the study protocol.
Arm/Group Title JE-CV Booster
Hide Arm/Group Description:
Participants previously received a single dose of JE-CV in the JEC02 trial and also received a booster dose of JE-CV in the current trial.
Overall Number of Participants Analyzed 345
Measure Type: Number
Unit of Measure: Percentage of participants
Day 0 (pre-vaccination) Number Analyzed 345 participants
80.3
Day 7 post-vaccination Number Analyzed 345 participants
96.2
Day 28 post-vaccination Number Analyzed 344 participants
100.0
Year 1 post-vaccination Number Analyzed 339 participants
99.4
Year 2 post-vaccination Number Analyzed 340 participants
98.8
Year 3 post-vaccination Number Analyzed 338 participants
99.1
Year 4 post-vaccination Number Analyzed 335 participants
98.2
Year 5 post-vaccination Number Analyzed 336 participants
98.2
7.Primary Outcome
Title Summary of Geometric Mean Titer of JE Virus Antibodies Before and Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV
Hide Description The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Time Frame Day 0 (pre-vaccination) and Days 7 and 28 and Year 1, 2, 3, 4, and 5 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Geometric mean titers of JE virus antibodies were assessed in the Full Analysis Set. Data for JE-CV Vaccine First Dose and Varicella Vaccine Groups were not analyzed for this outcome measure as pre-specified in the study protocol.
Arm/Group Title JE-CV Booster
Hide Arm/Group Description:
Participants previously received a single dose of JE-CV in the JEC02 trial and also received a booster dose of JE-CV in the current trial.
Overall Number of Participants Analyzed 345
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers (1/dilution)
Day 0 (pre-vaccination) Number Analyzed 345 participants
39.3
(33.7 to 45.8)
Day 7 post-vaccination Number Analyzed 345 participants
233
(193 to 281)
Day 28 post-vaccination Number Analyzed 344 participants
2259
(1930 to 2645)
Year 1 post-vaccination Number Analyzed 339 participants
596
(502 to 708)
Year 2 post-vaccination Number Analyzed 340 participants
368
(313 to 432)
Year 3 post-vaccination Number Analyzed 338 participants
301
(257 to 352)
Year 4 post-vaccination Number Analyzed 335 participants
249
(215 to 289)
Year 5 post-vaccination Number Analyzed 336 participants
161
(141 to 184)
8.Primary Outcome
Title Summary of Geometric Mean Titer Ratios of JE Virus Antibodies Up to 5 Years Following a Booster Dose of Live Attenuated JE-CV
Hide Description The presence of JE virus neutralizing antibodies was measured using a PRNT50 assay.
Time Frame Year 1, 2, 3, 4, and 5 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Geometric mean titer ratios of JE virus antibodies were assessed in the Full Analysis Set. Data for JE-CV Vaccine First Dose and Varicella Vaccine Groups were not analyzed for this outcome measure as pre-specified in the study protocol.
Arm/Group Title JE-CV Booster
Hide Arm/Group Description:
Participants previously received a single dose of JE-CV in the JEC02 trial and also received a booster dose of JE-CV in the current trial
Overall Number of Participants Analyzed 345
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titer ratios (1/dilution)
Year 2/Year 1 Number Analyzed 339 participants
0.615
(0.539 to 0.701)
Year 3/Year 2 Number Analyzed 338 participants
0.821
(0.734 to 0.919)
Year 4/Year 3 Number Analyzed 335 participants
0.827
(0.746 to 0.916)
Year 5/Year 4 Number Analyzed 335 participants
0.646
(0.584 to 0.715)
9.Primary Outcome
Title Number of Participants With Solicited Injection-Site Reactions and Systemic Reactions Following a Dose of Live Attenuated JE-CV or Varicella Vaccine
Hide Description Injection-site reactions: Pain, Erythema, and Swelling. Systemic reactions: Fever (Temperature), Headache, Malaise, and Myalgia. Grade 3 Injection-site reactions: Pain, Incapacitating, unable to perform usual activities. Erythema and Swelling, ≥5 cm. Grade 3 Systemic reactions: Fever, 39.0°C; Headache, Malaise, and Myalgia, Significant; prevents daily activities.
Time Frame Day 0 up to Day 14 post-vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Solicited injection-site and systemic reactions were assessed in the Safety Analysis Set.
Arm/Group Title JE-CV Booster JE-CV First Dose Varicella Vaccine Group
Hide Arm/Group Description:
Participants previously received a single dose of JE-CV in the JEC02 trial and also received a booster dose of JE-CV in the current trial.
JE naïve control participants received a single dose of JE-CV on Day 0 (Immunogenicity Control group).
JE naïve control participants received a varicella vaccination (Okavax®) on Day 0 (Safety Control group).
Overall Number of Participants Analyzed 345 46 59
Measure Type: Number
Unit of Measure: Participants
Injection-site Pain Number Analyzed 344 participants 46 participants 59 participants
73 13 12
Grade 3 Injection-site Pain Number Analyzed 344 participants 46 participants 59 participants
0 0 0
Injection-site Erythema Number Analyzed 344 participants 46 participants 59 participants
29 1 4
Grade 3 Injection-site Erythema Number Analyzed 344 participants 46 participants 59 participants
0 0 0
Injection-site Swelling Number Analyzed 344 participants 46 participants 59 participants
19 0 1
Grade 3 Injection-site Swelling Number Analyzed 344 participants 46 participants 59 participants
0 0 0
Fever Number Analyzed 344 participants 46 participants 59 participants
49 1 9
Grade 3 Fever Number Analyzed 344 participants 46 participants 59 participants
6 1 0
Headache Number Analyzed 344 participants 46 participants 59 participants
41 5 8
Grade 3 Headache Number Analyzed 344 participants 46 participants 59 participants
2 0 0
Malaise Number Analyzed 344 participants 46 participants 59 participants
49 6 6
Grade 3 Malaise Number Analyzed 344 participants 46 participants 59 participants
2 0 0
Myalgia Number Analyzed 344 participants 46 participants 59 participants
19 2 2
Grade 3 Myalgia Number Analyzed 344 participants 46 participants 59 participants
1 0 0
Time Frame Adverse event data were collected from Day 0 up Day 14 post-vaccination for solicited AEs, up to Day 28 post-vaccination for unsolicited AEs, and up to 5 years post-vaccination for SAEs.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title JE-CV Vaccine Booster JE-CV Vaccine First Dose Varicella Vaccine Group
Hide Arm/Group Description Participants previously received a single dose of JE-CV Vaccine in the JEC02 trial and also received a booster dose of JE-CV in the current trial. JE vaccine naïve control participants received a single dose of JE-CV on Day 0 (Immunogenicity Control group). JE vaccine naïve control participants received a varicella vaccination (Okavax®) on Day 0 (Safety Control group).
All-Cause Mortality
JE-CV Vaccine Booster JE-CV Vaccine First Dose Varicella Vaccine Group
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/345 (0.00%)      0/46 (0.00%)      0/59 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
JE-CV Vaccine Booster JE-CV Vaccine First Dose Varicella Vaccine Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/345 (0.87%)      0/46 (0.00%)      0/59 (0.00%)    
Infections and infestations       
Dengue fever * 1  2/345 (0.58%)  2 0/46 (0.00%)  0 0/59 (0.00%)  0
Nervous system disorders       
Febrile convulsion * 1  1/345 (0.29%)  1 0/46 (0.00%)  0 0/59 (0.00%)  0
1
Term from vocabulary, MedDRA 12
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.00%
JE-CV Vaccine Booster JE-CV Vaccine First Dose Varicella Vaccine Group
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   73/345 (21.16%)      13/46 (28.26%)      12/59 (20.34%)    
General disorders       
Injection site Pain * 1  73/345 (21.16%)  73 13/46 (28.26%)  13 12/59 (20.34%)  12
Injection site Erythema * 1  29/345 (8.41%)  29 1/46 (2.17%)  1 4/59 (6.78%)  4
Injection site Swelling * 1  19/345 (5.51%)  19 0/46 (0.00%)  0 1/59 (1.69%)  1
Fever * 1  49/345 (14.20%)  49 1/46 (2.17%)  1 9/59 (15.25%)  9
Malaise * 1  49/345 (14.20%)  49 6/46 (13.04%)  6 6/59 (10.17%)  6
Infections and infestations       
Rhinitis * 1  12/345 (3.48%)  12 1/46 (2.17%)  1 3/59 (5.08%)  3
Upper respiratory tract infection * 1  37/345 (10.72%)  41 3/46 (6.52%)  4 6/59 (10.17%)  6
Musculoskeletal and connective tissue disorders       
Myalgia * 1  19/345 (5.51%)  19 2/46 (4.35%)  2 2/59 (3.39%)  2
Nervous system disorders       
Headache * 1  41/345 (11.88%)  41 5/46 (10.87%)  5 8/59 (13.56%)  8
1
Term from vocabulary, MedDRA 12
*
Indicates events were collected by non-systematic assessment
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.
Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications
Results Point of Contact
Name/Title: Medical Director
Organization: Sanofi Pasteur Inc.
Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01190228     History of Changes
Other Study ID Numbers: JEC15
UTN: U1111-1113-3629 ( Other Identifier: WHO )
First Submitted: August 25, 2010
First Posted: August 27, 2010
Results First Submitted: August 31, 2017
Results First Posted: November 8, 2017
Last Update Posted: November 8, 2017