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Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Gardasil®

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ClinicalTrials.gov Identifier: NCT02993757
Recruitment Status : Completed
First Posted : December 15, 2016
Results First Posted : June 11, 2020
Last Update Posted : June 11, 2020
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 Dengue Fever
Dengue Hemorrhagic Fever
Human Papillomavirus Disease
Interventions Biological: CYD Dengue Vaccine
Biological: Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.
Enrollment 528
Recruitment Details Study participants were enrolled from 01 December 2016 to 16 April 2017 at 5 centers in Malaysia. A total of 528 participants were enrolled and randomized in study.
Pre-assignment Details As per protocol amendment 1, only dengue immune participants at baseline completed the dengue vaccination schedule and received 3 doses of CYD dengue vaccine, whereas the dengue non-immune participants received only 2 doses of CYD dengue vaccine. All participants were followed for safety up to 6 months after the last vaccination.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description Dengue immune participants (i.e., titers greater than or equal to (>=)10 (1/dilution [dil]) for at least one serotype with the parental dengue virus strains in the baseline sample) received 3 doses of CYD dengue vaccine 0.5 milliliter (mL) subcutaneously (SC) at Day 0, Month 6, and Month 12; whereas dengue non-immune participants (i.e., titers less than (<)10 (1/dil) for all serotypes with parental dengue virus strains with available and "valid" results in the baseline sample) received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL Intramuscular (IM), concomitantly with the first 2 doses of CYD dengue vaccine. Dengue immune participants (i.e., titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains in the baseline sample) received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants (i.e., titers <10 (1/dil) for all serotypes with parental dengue virus strains with available and "valid" results in the baseline sample) received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Period Title: Overall Study
Started 266 262
Safety Analysis Set (SafAS) [1] 263 260
Completed 102 84
Not Completed 164 178
Reason Not Completed
Non compliance with the protocol             155             170
Lost to Follow-up             1             0
Voluntary withdraw not due adverse event             8             8
[1]
SafAS was defined as participants who had received at least 1 dose of study vaccines.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration) Total
Hide Arm/Group Description Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine. Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine. Total of all reporting groups
Overall Number of Baseline Participants 266 262 528
Hide Baseline Analysis Population Description
Analysis was performed on all randomized participants.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 266 participants 262 participants 528 participants
10.4  (1.20) 10.5  (1.18) 10.4  (1.19)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 266 participants 262 participants 528 participants
Female
175
  65.8%
172
  65.6%
347
  65.7%
Male
91
  34.2%
90
  34.4%
181
  34.3%
Race and Ethnicity Not Collected   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 0 participants 0 participants 0 participants
0
[1]
Measure Analysis Population Description: Race and Ethnicity were not collected from any participant.
Dengue Seropositivity Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Dengue immune Number Analyzed 266 participants 262 participants 528 participants
109
  41.0%
88
  33.6%
197
  37.3%
Dengue non-immune Number Analyzed 266 participants 262 participants 528 participants
157
  59.0%
174
  66.4%
331
  62.7%
[1]
Measure Description:

Dengue immune participants were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains in the baseline sample.

Dengue non-immune participants were defined as participants with titers <10 (1/dil) for all serotypes with parental dengue virus strains with available and "valid" results in the baseline sample.

1.Primary Outcome
Title Geometric Mean Titers (GMTs) Against Each Gardasil Vaccine Human Papillomavirus (HPV) Antigen (HPV-6, HPV-11, HPV-16, HPV-18) 28 Days After Last Gardasil Vaccination in the Previously Dengue Immune Participants
Hide Description GMTs (measured in milli-Merck Units per mL [mMU/mL]) against each Gardasil HPV antigen (HPV-6, HPV-11, HPV-16, HPV-18) were assessed using competitive Luminex immunoassay (cLIA) method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Time Frame 28 days after the last Gardasil vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on full analysis set (FAS) that included subset of participants who received at least one dose of each of study vaccines (CYD and Gardasil), analyzed by baseline dengue status & vaccine group randomized. Here,'overall number of participants analyzed' = participants evaluable and had available data for this outcome measure.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 104 86
Geometric Mean (95% Confidence Interval)
Unit of Measure: mMU/mL
HPV-6
420
(327 to 539)
428
(314 to 583)
HPV-11
1288
(1089 to 1522)
1601
(1323 to 1937)
HPV-16
6221
(5093 to 7598)
7629
(6142 to 9475)
HPV-18
829
(682 to 1007)
1042
(858 to 1266)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine + Gardasil (Concomitant Administration), CYD Dengue Vaccine + Gardasil (Sequential Administration)
Comments Antigen HPV-6
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.982
Confidence Interval (2-Sided) 95%
0.664 to 1.45
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine + Gardasil (Concomitant Administration), CYD Dengue Vaccine + Gardasil (Sequential Administration)
Comments Antigen HPV-11
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.804
Confidence Interval (2-Sided) 95%
0.626 to 1.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine + Gardasil (Concomitant Administration), CYD Dengue Vaccine + Gardasil (Sequential Administration)
Comments Antigen HPV-16
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.815
Confidence Interval (2-Sided) 95%
0.608 to 1.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine + Gardasil (Concomitant Administration), CYD Dengue Vaccine + Gardasil (Sequential Administration)
Comments Antigen HPV-18
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.795
Confidence Interval (2-Sided) 95%
0.603 to 1.05
Estimation Comments [Not Specified]
2.Primary Outcome
Title Geometric Mean Titers Against Each Parental Dengue Virus Serotype 28 Days After Third CYD Dengue Vaccination in the Previously Dengue Immune Participants
Hide Description The GMTs against each of the four parental dengue virus serotypes (1, 2, 3, and 4) of CYD dengue vaccine was assessed using the 50% plaque reduction neutralization test (PRNT50) assay. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Time Frame 28 days after third CYD dengue vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants evaluable and had available data for this outcome measure.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 102 84
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer (1/dilution)
Serotype 1
447
(303 to 659)
453
(313 to 656)
Serotype 2
561
(408 to 771)
717
(526 to 977)
Serotype 3
460
(354 to 596)
549
(411 to 734)
Serotype 4
323
(263 to 398)
303
(255 to 359)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine + Gardasil (Concomitant Administration), CYD Dengue Vaccine + Gardasil (Sequential Administration)
Comments Serotype 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.987
Confidence Interval (2-Sided) 95%
0.574 to 1.70
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine + Gardasil (Concomitant Administration), CYD Dengue Vaccine + Gardasil (Sequential Administration)
Comments Serotype 2
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.783
Confidence Interval (2-Sided) 95%
0.500 to 1.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine + Gardasil (Concomitant Administration), CYD Dengue Vaccine + Gardasil (Sequential Administration)
Comments Serotype 3
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.836
Confidence Interval (2-Sided) 95%
0.568 to 1.23
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection CYD Dengue Vaccine + Gardasil (Concomitant Administration), CYD Dengue Vaccine + Gardasil (Sequential Administration)
Comments Serotype 4
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 1.07
Confidence Interval (2-Sided) 95%
0.813 to 1.40
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Seroconversion Against Each Gardasil HPV Antigen (HPV-6, HPV-11, HPV-16, HPV-18) 28 Days After Last Dose of Gardasil in the Previously Dengue Immune Participants
Hide Description Neutralizing antibodies against each Gardasil HPV antigen (HPV-6, HPV-11, HPV-16, HPV-18) was assessed using cLIA method. Seroconversion was defined as changing serostatus from seronegative at baseline to seropositive (participants with a pre-vaccination titer < lower limit of quantification [LLOQ] (mMU/mL) to a post-vaccination titer >=LLOQ) or >=4-fold rise in antibody titer if seropositive at baseline. The LLOQ for HPV-6 and HPV-16 was 11 mMU/mL, 8 mMU/mL for HPV-11, and 10 mMU/mL for HPV-18. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Time Frame 28 days after the last Gardasil vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants evaluable and had available data for this outcome measure.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 103 81
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
HPV-6
98.1
(93.2 to 99.8)
100.0
(95.5 to 100.0)
HPV-11
100.0
(96.5 to 100.0)
100.0
(95.5 to 100.0)
HPV-16
100.0
(96.5 to 100.0)
100.0
(95.5 to 100.0)
HPV-18
100.0
(96.5 to 100.0)
100.0
(95.5 to 100.0)
4.Secondary Outcome
Title Geometric Mean Titers Against Each Gardasil HPV Antigen (HPV-6, HPV-11, HPV-16, HPV-18) at Day 0 and 28 Days After Each Dose of Gardasil in the Previously Dengue Immune Participants
Hide Description The GMTs (measured in mMU/mL) against each Gardasil HPV antigen (HPV-6, HPV-11, HPV-16, HPV-18) was assessed using cLIA method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Time Frame Day 0 (pre-vaccination) and 28 days after Gardasil vaccination 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants evaluable and had available data for this outcome measure and 'Number analyzed' = participants with available data for each specified categories.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 109 88
Geometric Mean (95% Confidence Interval)
Unit of Measure: mMU/mL
HPV-6: Day 0 Number Analyzed 108 participants 82 participants
5.70
(5.46 to 5.95)
5.61
(5.46 to 5.77)
HPV-6: 28 days post vaccination 1 Number Analyzed 107 participants 88 participants
54.9
(45.0 to 66.9)
61.8
(49.7 to 76.9)
HPV-6: 28 days post vaccination 2 Number Analyzed 104 participants 86 participants
420
(327 to 539)
428
(314 to 583)
HPV-11: Day 0 Number Analyzed 108 participants 82 participants
4.16
(3.92 to 4.41)
4.00 [1] 
(NA to NA)
HPV-11: 28 days post vaccination 1 Number Analyzed 107 participants 88 participants
58.1
(47.6 to 71.0)
78.5
(62.5 to 98.6)
HPV-11: 28 days post vaccination 2 Number Analyzed 104 participants 86 participants
1288
(1089 to 1522)
1601
(1323 to 1937)
HPV-16: Day 0 Number Analyzed 108 participants 82 participants
5.62
(5.38 to 5.87)
5.50 [1] 
(NA to NA)
HPV-16: 28 days post vaccination 1 Number Analyzed 107 participants 88 participants
148
(119 to 185)
150
(116 to 193)
HPV-16: 28 days post vaccination 2 Number Analyzed 104 participants 86 participants
6221
(5093 to 7598)
7629
(6142 to 9475)
HPV-18: Day 0 Number Analyzed 108 participants 82 participants
5.26
(5.03 to 5.50)
5.06
(4.94 to 5.18)
HPV-18: 28 days post vaccination 1 Number Analyzed 107 participants 88 participants
23.5
(18.7 to 29.4)
31.6
(24.9 to 40.0)
HPV-18: 28 days post vaccination 2 Number Analyzed 104 participants 86 participants
829
(682 to 1007)
1042
(858 to 1266)
[1]
The 95% confidence interval was not computable, since all participants had the same value.
5.Secondary Outcome
Title Geometric Mean Titers Against Each Dengue Virus Serotype of CYD Dengue Vaccine at Day 0 and 28 Days After Each Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Hide Description The GMTs against each of the four parental dengue virus serotypes (1, 2, 3, and 4) of CYD dengue vaccine was assessed using the PRNT50 assay. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Time Frame Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants evaluable and had available data for this outcome measure and 'Number analyzed' = participants with available data for each specified categories.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 109 88
Geometric Mean (95% Confidence Interval)
Unit of Measure: titer (1/dilution)
Serotype 1: Day 0 Number Analyzed 109 participants 88 participants
62.3
(40.7 to 95.5)
81.5
(49.4 to 135)
Serotype 1: 28 days post vaccination 1 Number Analyzed 107 participants 88 participants
382
(245 to 597)
449
(268 to 752)
Serotype 1: 28 days post vaccination 2 Number Analyzed 104 participants 87 participants
403
(270 to 602)
529
(342 to 819)
Serotype 1: 28 days post vaccination 3 Number Analyzed 102 participants 84 participants
447
(303 to 659)
453
(313 to 656)
Serotype 2: Day 0 Number Analyzed 109 participants 88 participants
110
(75.5 to 160)
130
(84.0 to 201)
Serotype 2: 28 days post-vaccination 1 Number Analyzed 107 participants 88 participants
750
(500 to 1124)
848
(541 to 1330)
Serotype 2: 28 days post-vaccination 2 Number Analyzed 104 participants 87 participants
728
(519 to 1019)
937
(654 to 1342)
Serotype 2: 28 days post-vaccination 3 Number Analyzed 102 participants 84 participants
561
(408 to 771)
717
(526 to 977)
Serotype 3: Day 0 Number Analyzed 109 participants 87 participants
72.3
(52.7 to 99.2)
96.7
(64.9 to 144)
Serotype 3: 28 days post-vaccination 1 Number Analyzed 106 participants 88 participants
432
(304 to 614)
517
(355 to 755)
Serotype 3: 28 days post-vaccination 2 Number Analyzed 104 participants 87 participants
389
(299 to 506)
543
(403 to 731)
Serotype 3: 28 days post-vaccination 3 Number Analyzed 102 participants 84 participants
460
(354 to 596)
549
(411 to 734)
Serotype 4: Day 0 Number Analyzed 109 participants 88 participants
26.3
(18.8 to 36.7)
23.7
(16.2 to 34.8)
Serotype 4: 28 days post-vaccination 1 Number Analyzed 107 participants 88 participants
330
(234 to 464)
286
(204 to 401)
Serotype 4: 28 days post-vaccination 2 Number Analyzed 104 participants 87 participants
284
(229 to 352)
282
(225 to 353)
Serotype 4: 28 days post-vaccination 3 Number Analyzed 102 participants 84 participants
323
(263 to 398)
303
(255 to 359)
6.Secondary Outcome
Title Percentage of Participants With Neutralizing Antibody Titers Against Each of the 4 Dengue Virus Serotypes of CYD Dengue Vaccine at Day 0 And 28 Days After Each Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Hide Description Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (1, 2, 3, and 4) was measured by PRNT50. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Time Frame Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants evaluable and had available data for this outcome measure and 'Number analyzed' = participants with available data for each specified categories.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 109 88
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Serotype 1: Day 0 Number Analyzed 109 participants 88 participants
66.1
(56.4 to 74.9)
72.7
(62.2 to 81.7)
Serotype 1: 28 days post vaccination 1 Number Analyzed 107 participants 88 participants
91.6
(84.6 to 96.1)
90.9
(82.9 to 96.0)
Serotype 1: 28 days post vaccination 2 Number Analyzed 104 participants 87 participants
96.2
(90.4 to 98.9)
95.4
(88.6 to 98.7)
Serotype 1: 28 days post vaccination 3 Number Analyzed 102 participants 84 participants
95.1
(88.9 to 98.4)
100.0
(95.7 to 100.0)
Serotype 2: Day 0 Number Analyzed 109 participants 88 participants
83.5
(75.2 to 89.9)
81.8
(72.2 to 89.2)
Serotype 2: 28 days post-vaccination 1 Number Analyzed 107 participants 88 participants
93.5
(87.0 to 97.3)
92.0
(84.3 to 96.7)
Serotype 2: 28 days post-vaccination 2 Number Analyzed 104 participants 87 participants
99.0
(94.8 to 100.0)
97.7
(91.9 to 99.7)
Serotype 2: 28 days post-vaccination 3 Number Analyzed 102 participants 84 participants
97.1
(91.6 to 99.4)
98.8
(93.5 to 100.0)
Serotype 3: Day 0 Number Analyzed 109 participants 87 participants
89.0
(81.6 to 94.2)
86.2
(77.1 to 92.7)
Serotype 3: 28 days post-vaccination 1 Number Analyzed 106 participants 88 participants
96.2
(90.6 to 99.0)
97.7
(92.0 to 99.7)
Serotype 3: 28 days post-vaccination 2 Number Analyzed 104 participants 87 participants
100.0
(96.5 to 100.0)
100.0
(95.8 to 100.0)
Serotype 3: 28 days post-vaccination 3 Number Analyzed 102 participants 84 participants
99.0
(94.7 to 100.0)
100.0
(95.7 to 100.0)
Serotype 4: Day 0 Number Analyzed 109 participants 88 participants
59.6
(49.8 to 68.9)
54.5
(43.6 to 65.2)
Serotype 4: 28 days post-vaccination 1 Number Analyzed 107 participants 88 participants
93.5
(87.0 to 97.3)
98.9
(93.8 to 100.0)
Serotype 4: 28 days post-vaccination 2 Number Analyzed 104 participants 87 participants
100.0
(96.5 to 100.0)
100.0
(95.8 to 100.0)
Serotype 4: 28 days post-vaccination 3 Number Analyzed 102 participants 84 participants
100.0
(96.4 to 100.0)
100.0
(95.7 to 100.0)
7.Secondary Outcome
Title Percentage of Participants With Neutralizing Antibody Titers Above Pre-defined Thresholds Against at Least 1,2,3,or4 Serotypes of CYD Dengue Vaccine at Day 0 And 28 Days After Each Dose of CYD Dengue Vaccination in Previously Dengue Immune Participants
Hide Description Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (1, 2, 3, and 4) was measured by PRNT50. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains. Percentage of participants with neutralizing antibody titers above pre-defined thresholds (>=10 and >=100 [1/dil]) against at least 1, 2, 3, or 4 serotypes of CYD dengue vaccine were reported.
Time Frame Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination
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Hide Analysis Population Description
Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants evaluable and had available data for this outcome measure and 'Number analyzed' = participants with available data for each specified categories.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 109 88
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
At least 1 Serotype: Day 0: >=10 (1/dil) Number Analyzed 109 participants 88 participants
100.0
(96.7 to 100.0)
100.0
(95.9 to 100.0)
At least 1 Serotype: Day 0: >=100 (1/dil) Number Analyzed 109 participants 88 participants
90.8
(83.8 to 95.5)
88.6
(80.1 to 94.4)
At least 1 Serotype:post vaccination 1:>=10(1/dil) Number Analyzed 107 participants 88 participants
97.2
(92.0 to 99.4)
100.0
(95.9 to 100.0)
At least 1 Serotype:post vaccination1:>=100(1/dil) Number Analyzed 107 participants 88 participants
95.3
(89.4 to 98.5)
96.6
(90.4 to 99.3)
At least 1 Serotype:post vaccination 2:>=10(1/dil) Number Analyzed 104 participants 87 participants
100.0
(96.5 to 100.0)
100.0
(95.8 to 100.0)
At least 1 Serotype:post vaccination2:>=100(1/dil) Number Analyzed 104 participants 87 participants
96.2
(90.4 to 98.9)
98.9
(93.8 to 100.0)
At least 1 Serotype:post vaccination 3:>=10(1/dil) Number Analyzed 102 participants 84 participants
100.0
(96.4 to 100.0)
100.0
(95.7 to 100.0)
At least 1 Serotype:post vaccination3:>=100(1/dil) Number Analyzed 102 participants 84 participants
98.0
(93.1 to 99.8)
97.6
(91.7 to 99.7)
At least 2 Serotypes: Day 0: >=10 (1/dil) Number Analyzed 109 participants 88 participants
84.4
(76.2 to 90.6)
81.8
(72.2 to 89.2)
At least 2 Serotypes: Day 0: >=100 (1/dil) Number Analyzed 109 participants 88 participants
34.9
(26.0 to 44.6)
39.8
(29.5 to 50.8)
At least 2 Serotypes:post vaccination1:>=10(1/dil) Number Analyzed 107 participants 88 participants
94.4
(88.2 to 97.9)
97.7
(92.0 to 99.7)
At least 2Serotypes:post vaccination1:>=100(1/dil) Number Analyzed 107 participants 88 participants
85.0
(76.9 to 91.2)
80.7
(70.9 to 88.3)
At least 2 Serotypes:post vaccination2:>=10(1/dil) Number Analyzed 104 participants 87 participants
100.0
(96.5 to 100.0)
100.0
(95.8 to 100.0)
At least 2Serotypes:post vaccination2:>=100(1/dil) Number Analyzed 104 participants 87 participants
84.6
(76.2 to 90.9)
92.0
(84.1 to 96.7)
At least 2 Serotypes:post vaccination3:>=10(1/dil) Number Analyzed 102 participants 84 participants
100.0
(96.4 to 100.0)
100.0
(95.7 to 100.0)
At least 2Serotypes:post vaccination3:>=100(1/dil) Number Analyzed 102 participants 84 participants
93.1
(86.4 to 97.2)
94.0
(86.7 to 98.0)
At least 3 Serotypes:Day 0: >=10 (1/dil) Number Analyzed 109 participants 88 participants
71.6
(62.1 to 79.8)
69.3
(58.6 to 78.7)
At least 3 Serotypes:Day 0: >=100 (1/dil) Number Analyzed 109 participants 88 participants
23.9
(16.2 to 33.0)
27.3
(18.3 to 37.8)
At least 3 Serotypes:post vaccination1:>=10(1/dil) Number Analyzed 107 participants 88 participants
92.5
(85.8 to 96.7)
92.0
(84.3 to 96.7)
At least 3Serotypes:post vaccination1:>=100(1/dil) Number Analyzed 107 participants 88 participants
75.7
(66.5 to 83.5)
73.9
(63.4 to 82.7)
At least 3 Serotypes:post vaccination2:>=10(1/dil) Number Analyzed 104 participants 87 participants
99.0
(94.8 to 100.0)
98.9
(93.8 to 100.0)
At least 3Serotypes:post vaccination2:>=100(1/dil) Number Analyzed 104 participants 87 participants
77.9
(68.7 to 85.4)
86.2
(77.1 to 92.7)
At least 3 Serotypes:post vaccination3:>=10(1/dil) Number Analyzed 102 participants 84 participants
97.1
(91.6 to 99.4)
100.0
(95.7 to 100.0)
At least 3Serotypes:post vaccination3:>=100(1/dil) Number Analyzed 102 participants 84 participants
83.3
(74.7 to 90.0)
88.1
(79.2 to 94.1)
At least 4 Serotypes:Day 0: >=10 (1/dil) Number Analyzed 109 participants 87 participants
42.2
(32.8 to 52.0)
43.7
(33.1 to 54.7)
At least 4 Serotypes:Day 0: >=100 (1/dil) Number Analyzed 109 participants 87 participants
6.4
(2.6 to 12.8)
12.6
(6.5 to 21.5)
At least 4 Serotypes:post vaccination1:>=10(1/dil) Number Analyzed 106 participants 88 participants
90.6
(83.3 to 95.4)
89.8
(81.5 to 95.2)
At least 4Serotypes:post vaccination1:>=100(1/dil) Number Analyzed 106 participants 88 participants
60.4
(50.4 to 69.7)
62.5
(51.5 to 72.6)
At least 4 Serotypes:post vaccination2:>=10(1/dil) Number Analyzed 104 participants 87 participants
96.2
(90.4 to 98.9)
94.3
(87.1 to 98.1)
At least 4Serotypes:post vaccination2:>=100(1/dil) Number Analyzed 104 participants 87 participants
67.3
(57.4 to 76.2)
75.9
(65.5 to 84.4)
At least 4 Serotypes:post vaccination3:>=10(1/dil) Number Analyzed 102 participants 84 participants
94.1
(87.6 to 97.8)
98.8
(93.5 to 100.0)
At least 4Serotypes:post vaccination3:>=100(1/dil) Number Analyzed 102 participants 84 participants
72.5
(62.8 to 80.9)
77.4
(67.0 to 85.8)
8.Secondary Outcome
Title Number of Participants Reporting Immediate Adverse Events (AEs) Following Vaccination With Gardasil or CYD Dengue Vaccine
Hide Description Any unsolicited systemic AE occurred during the first 30 minutes post-vaccination was recorded on the case report form (CRF) as immediate AE. At Visit 1 and Visit 4, participants from Group 1 received both Gardasil and CYD vaccination and participants from Group 2 received only Gardasil vaccination. At Visit 2 and Visit 5, only participants from Group 2 received CYD vaccination whereas the participants from Group 1 received no vaccination.
Time Frame Within 30 minutes after any and each vaccination
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Analysis was performed on safety analysis set (SafAS) which included participants who have received at least one dose of the study vaccines. Here, 'Number analyzed' = participants with available data for each specified categories.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 263 260
Measure Type: Count of Participants
Unit of Measure: Participants
Post any vaccination Number Analyzed 263 participants 260 participants
0
   0.0%
3
   1.2%
Post vaccination 1 (Visit 1) Number Analyzed 263 participants 260 participants
0
   0.0%
1
   0.4%
Post CYD vaccination 1 (Visit 2) Number Analyzed 0 participants 256 participants
1
   0.4%
Post vaccination 2 (Visit 4) Number Analyzed 257 participants 256 participants
0
   0.0%
0
   0.0%
Post CYD vaccination 2 (Visit 5) Number Analyzed 0 participants 249 participants
1
   0.4%
Post CYD vaccination 3 (Visit 7) Number Analyzed 103 participants 83 participants
0
   0.0%
0
   0.0%
9.Secondary Outcome
Title Number of Participants Reporting Solicited Injection Site Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine
Hide Description A solicited reaction (SR) was an adverse reaction (AR) observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRF and considered as related to vaccination. Solicited injection site reactions included pain, erythema, and swelling.
Time Frame Up to 7 days after any and each vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on SafAS. Here, 'Number analyzed' = participants with available data for each specified categories.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 263 260
Measure Type: Count of Participants
Unit of Measure: Participants
Pain: Post any CYD/Gardasil vaccine Number Analyzed 260 participants 258 participants
206
  79.2%
193
  74.8%
Pain: Post CYD/Gardasil vaccination 1 Number Analyzed 260 participants 258 participants
163
  62.7%
157
  60.9%
Pain: Post CYD/Gardasil vaccination 2 Number Analyzed 256 participants 254 participants
151
  59.0%
141
  55.5%
Pain: Post CYD vaccination 3 Number Analyzed 103 participants 83 participants
33
  32.0%
24
  28.9%
Erythema: Post any CYD/Gardasil vaccine Number Analyzed 260 participants 258 participants
45
  17.3%
38
  14.7%
Erythema: Post CYD/Gardasil vaccination 1 Number Analyzed 260 participants 258 participants
30
  11.5%
29
  11.2%
Erythema: Post CYD/Gardasil vaccination 2 Number Analyzed 256 participants 254 participants
25
   9.8%
19
   7.5%
Erythema: Post CYD vaccination 3 Number Analyzed 103 participants 83 participants
9
   8.7%
2
   2.4%
Swelling: Post any CYD/Gardasil vaccine Number Analyzed 260 participants 258 participants
43
  16.5%
31
  12.0%
Swelling: Post CYD/Gardasil vaccination 1 Number Analyzed 260 participants 258 participants
22
   8.5%
22
   8.5%
Swelling: Post CYD/Gardasil vaccination 2 Number Analyzed 256 participants 254 participants
30
  11.7%
18
   7.1%
Swelling: Post CYD vaccination 3 Number Analyzed 103 participants 83 participants
9
   8.7%
3
   3.6%
10.Secondary Outcome
Title Number of Participants Reporting Solicited Systemic Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine
Hide Description A SR was an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia. At Visit 1 and Visit 4, participants from Group 1 received both Gardasil and CYD vaccination and participants from Group 2 received only Gardasil vaccination. At Visit 2 and Visit 5, only participants from Group 2 received CYD vaccination whereas the participants from Group 1 received no vaccination.
Time Frame Up to 14 days after any and each vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on SafAS. Here, 'Number analyzed' = participants with available data for each specified categories.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 263 260
Measure Type: Count of Participants
Unit of Measure: Participants
Fever: Post any vaccination Number Analyzed 259 participants 258 participants
36
  13.9%
47
  18.2%
Fever: Post vaccination 1 (Visit 1) Number Analyzed 257 participants 258 participants
21
   8.2%
8
   3.1%
Fever: Post CYD vaccination 1 (Visit 2) Number Analyzed 0 participants 255 participants
15
   5.9%
Fever: Post vaccination 2 (Visit 4) Number Analyzed 252 participants 253 participants
10
   4.0%
11
   4.3%
Fever: Post CYD vaccination 2 (Visit 5) Number Analyzed 0 participants 249 participants
12
   4.8%
Fever: Post CYD vaccination 3 (Visit 7) Number Analyzed 103 participants 83 participants
8
   7.8%
6
   7.2%
Headache: Post any vaccination Number Analyzed 260 participants 258 participants
125
  48.1%
146
  56.6%
Headache: Post vaccination 1 (Visit 1) Number Analyzed 260 participants 258 participants
99
  38.1%
93
  36.0%
Headache: Post CYD vaccination 1 (Visit 2) Number Analyzed 0 participants 255 participants
73
  28.6%
Headache: Post vaccination 2 (Visit 4) Number Analyzed 256 participants 254 participants
61
  23.8%
70
  27.6%
Headache: Post CYD vaccination 2 (Visit 5) Number Analyzed 0 participants 249 participants
51
  20.5%
Headache: Post CYD vaccination 3 (Visit 7) Number Analyzed 103 participants 83 participants
15
  14.6%
17
  20.5%
Malaise: Post any vaccination Number Analyzed 260 participants 258 participants
111
  42.7%
137
  53.1%
Malaise: Post vaccination 1 (Visit 1) Number Analyzed 260 participants 258 participants
82
  31.5%
78
  30.2%
Malaise: Post CYD vaccination 1 (Visit 2) Number Analyzed 0 participants 255 participants
69
  27.1%
Malaise: Post vaccination 2 (Visit 4) Number Analyzed 256 participants 254 participants
57
  22.3%
54
  21.3%
Malaise: Post CYD vaccination 2 (Visit 5) Number Analyzed 0 participants 249 participants
40
  16.1%
Malaise: Post CYD vaccination 3 (Visit 7) Number Analyzed 103 participants 83 participants
20
  19.4%
17
  20.5%
Myalgia: Post any vaccination Number Analyzed 260 participants 258 participants
127
  48.8%
156
  60.5%
Myalgia: Post vaccination 1 (Visit 1) Number Analyzed 260 participants 258 participants
93
  35.8%
94
  36.4%
Myalgia: Post CYD vaccination 1 (Visit 2) Number Analyzed 0 participants 255 participants
63
  24.7%
Myalgia: Post vaccination 2 (Visit 4) Number Analyzed 256 participants 254 participants
72
  28.1%
70
  27.6%
Myalgia: Post CYD vaccination 2 (Visit 5) Number Analyzed 0 participants 249 participants
43
  17.3%
Myalgia: Post CYD vaccination 3 (Visit 7) Number Analyzed 103 participants 83 participants
16
  15.5%
13
  15.7%
Asthenia: Post any vaccination Number Analyzed 260 participants 258 participants
133
  51.2%
132
  51.2%
Asthenia: Post vaccination 1 (Visit 1) Number Analyzed 260 participants 258 participants
101
  38.8%
89
  34.5%
Asthenia: Post CYD vaccination 1 (Visit 2) Number Analyzed 0 participants 255 participants
63
  24.7%
Asthenia: Post vaccination 2 (Visit 4) Number Analyzed 256 participants 254 participants
74
  28.9%
46
  18.1%
Asthenia: Post CYD vaccination 2 (Visit 5) Number Analyzed 0 participants 249 participants
35
  14.1%
Asthenia: Post CYD vaccination 3 (Visit 7) Number Analyzed 103 participants 83 participants
19
  18.4%
16
  19.3%
11.Secondary Outcome
Title Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With Gardasil or CYD Dengue Vaccine
Hide Description An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRF in terms of diagnosis and/or onset post-vaccination. At Visit 1 and Visit 4, participants from Group 1 received both Gardasil and CYD vaccination and participants from Group 2 received only Gardasil vaccination. At Visit 2 and Visit 5, only participants from Group 2 received CYD vaccination whereas the participants from Group 1 received no vaccination.
Time Frame Up to 28 days after any and each vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on SafAS. Here, 'Number analyzed' = participants with available data for each specified categories.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 263 260
Measure Type: Count of Participants
Unit of Measure: Participants
Post any vaccination Number Analyzed 263 participants 260 participants
54
  20.5%
91
  35.0%
Post vaccination 1 (Visit 1) Number Analyzed 263 participants 260 participants
34
  12.9%
38
  14.6%
Post CYD vaccination 1 (Visit 2) Number Analyzed 0 participants 256 participants
38
  14.8%
Post vaccination 2 (Visit 4) Number Analyzed 257 participants 256 participants
24
   9.3%
22
   8.6%
Post CYD vaccination 2 (Visit 5) Number Analyzed 0 participants 249 participants
28
  11.2%
Post CYD vaccination 3 (Visit 7) Number Analyzed 103 participants 83 participants
5
   4.9%
7
   8.4%
12.Secondary Outcome
Title Number of Participants Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Gardasil or CYD Dengue Vaccine
Hide Description AESI were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine. At Visit 1 and Visit 4, participants from Group 1 received both Gardasil and CYD vaccination and participants from Group 2 received only Gardasil vaccination. At Visit 2 and Visit 5, only participants from Group 2 received CYD vaccination whereas the participants from Group 1 received no vaccination.
Time Frame Within 7 days after any and each vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on SafAS. Here, 'Number analyzed' = participants with available data for each specified categories.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 263 260
Measure Type: Count of Participants
Unit of Measure: Participants
Post any vaccination Number Analyzed 263 participants 260 participants
0
   0.0%
0
   0.0%
Post vaccination 1 (Visit 1) Number Analyzed 263 participants 260 participants
0
   0.0%
0
   0.0%
Post CYD vaccination 1 (Visit 2) Number Analyzed 0 participants 256 participants
0
   0.0%
Post vaccination 2 (Visit 4) Number Analyzed 257 participants 256 participants
0
   0.0%
0
   0.0%
Post CYD vaccination 2 (Visit 5) Number Analyzed 0 participants 249 participants
0
   0.0%
Post CYD vaccination 3 (Visit 7) Number Analyzed 103 participants 83 participants
0
   0.0%
0
   0.0%
13.Secondary Outcome
Title Number of Participants Reporting Serious Adverse Events (SAEs) Including Serious Adverse Event of Special Interests Following Vaccination With Gardasil or CYD Dengue Vaccine
Hide Description SAEs were AEs that resulted in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event. An AESIs were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine.
Time Frame From Day 0 up to 6 months after the last Gardasil or CYD vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was performed on SafAS.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description:
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 263 260
Measure Type: Count of Participants
Unit of Measure: Participants
SAE
11
   4.2%
8
   3.1%
Serious AESI
1
   0.4%
2
   0.8%
14.Secondary Outcome
Title Number of Participants Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Gardasil or CYD Dengue Vaccine
Hide Description Hospitalized suspected dengue case was defined as an acute febrile illness with diagnosis of dengue requiring hospitalization (with bed attribution). In such cases, 1 unplanned acute blood sample (within the first 5 days after fever onset) was collected for virological confirmation of hospitalized suspected dengue case. A suspected case was considered VCD if there was a detection of wild type dengue virus by dengue non-structural protein 1 antigen enzyme-linked immunosorbent assay and/or dengue reverse transcriptase-polymerase chain reactions.
Time Frame From Day 0 up to 6 months after the last Gardasil or CYD vaccination
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Hide Analysis Population Description
Analysis was performed on SafAS.
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
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Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine.
Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
Overall Number of Participants Analyzed 263 260
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.4%
1
   0.4%
Time Frame The AE data were collected from Day 0 up to Day 28 post any vaccination. SR were collected from Day 0 up to Day 14 post any vaccination. The SAEs were collected throughout the trial, i.e. 6 months after last Gardasil or CYD vaccination.
Adverse Event Reporting Description The SR was an AE that was prelisted (i.e., solicited) in the electronic CRF and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRF (i.e., solicited) in terms of diagnosis and/or onset post-vaccination. Analysis was performed on SafAS.
 
Arm/Group Title CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Hide Arm/Group Description Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM, concomitantly with the first 2 doses of CYD dengue vaccine. Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine.
All-Cause Mortality
CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Affected / at Risk (%) Affected / at Risk (%)
Total   0/263 (0.00%)      0/260 (0.00%)    
Hide Serious Adverse Events
CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/263 (4.18%)      8/260 (3.08%)    
Infections and infestations     
Appendicitis  1  1/263 (0.38%)  1 1/260 (0.38%)  1
Chikungunya Virus Infection  1  1/263 (0.38%)  1 0/260 (0.00%)  0
Dengue Fever  1  1/263 (0.38%)  1 2/260 (0.77%)  2
Gastroenteritis  1  1/263 (0.38%)  1 0/260 (0.00%)  0
Gingival Abscess  1  0/263 (0.00%)  0 1/260 (0.38%)  1
Influenza  1  1/263 (0.38%)  1 0/260 (0.00%)  0
Pneumonia Mycoplasmal  1  1/263 (0.38%)  1 0/260 (0.00%)  0
Tonsillitis  1  1/263 (0.38%)  1 0/260 (0.00%)  0
Viral Infection  1  1/263 (0.38%)  1 0/260 (0.00%)  0
Injury, poisoning and procedural complications     
Fall  1  0/263 (0.00%)  0 1/260 (0.38%)  1
Sports Injury  1  0/263 (0.00%)  0 2/260 (0.77%)  2
Tendon Rupture  1  1/263 (0.38%)  1 0/260 (0.00%)  0
Renal and urinary disorders     
Glomerulonephritis Acute  1  1/263 (0.38%)  1 0/260 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Asthma  1  2/263 (0.76%)  2 1/260 (0.38%)  1
Tonsillar Hypertrophy  1  0/263 (0.00%)  0 1/260 (0.38%)  1
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
CYD Dengue Vaccine + Gardasil (Concomitant Administration) CYD Dengue Vaccine + Gardasil (Sequential Administration)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   233/263 (88.59%)      235/260 (90.38%)    
General disorders     
Asthenia  1  133/263 (50.57%)  194 132/260 (50.77%)  249
Injection Site Erythema  1  45/263 (17.11%)  99 38/260 (14.62%)  63
Injection Site Pain  1  206/263 (78.33%)  532 193/260 (74.23%)  452
Injection Site Swelling  1  43/263 (16.35%)  89 31/260 (11.92%)  48
Malaise  1  111/263 (42.21%)  159 137/260 (52.69%)  260
Pyrexia  1 [1]  39/263 (14.83%)  43 53/260 (20.38%)  61
Infections and infestations     
Upper Respiratory Tract Infection  1  20/263 (7.60%)  21 30/260 (11.54%)  37
Musculoskeletal and connective tissue disorders     
Myalgia  1  127/263 (48.29%)  181 156/260 (60.00%)  283
Nervous system disorders     
Headache  1 [2]  126/263 (47.91%)  178 147/260 (56.54%)  311
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
[1]
Pyrexia events that occurred after 14 days post-vaccination were considered as unsolicited AE.
[2]
Headache events that occurred after 14 days post-vaccination were considered as unsolicited AE.
Change of population for non-inferiority reduced to dengue immune participants & time window for 3rd vaccination not reached(study hold),hence non-inferiority analysis not performed & immunogenicity was performed on FAS & not on Per Protocol Set.
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 Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable participant 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
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Name/Title: Trial Transparency Team
Organization: Sanofi Pasteur
Phone: 800-633-1610 ext 1#
EMail: Contact-US@sanofi.com
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Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT02993757    
Other Study ID Numbers: CYD67
U1111-1161-3376 ( Other Identifier: WHO )
2019-003135-36 ( EudraCT Number )
First Submitted: December 12, 2016
First Posted: December 15, 2016
Results First Submitted: May 21, 2020
Results First Posted: June 11, 2020
Last Update Posted: June 11, 2020