Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Gardasil®
Study Details
Study Description
Brief Summary
The aim of the study was to assess the safety and immunogenicity of the CYD dengue vaccine and Gardasil (Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant) when administered concomitantly or sequentially.
Primary objectives:
-
To demonstrate that the humoral immune response (in terms of geometric mean titers [GMTs]) to Gardasil after concomitant administration was non-inferior to sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Gardasil.
-
To demonstrate that the humoral immune response to the CYD dengue vaccine after concomitant administration was non-inferior to sequential administration with Gardasil measured 28 days after the last dose of the CYD dengue vaccine.
Secondary Objectives:
-
To demonstrate that the humoral immune response (in terms of seroconversion) to Gardasil vaccine after concomitant administration was non-inferior to sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Gardasil.
-
To describe the humoral immune response to Gardasil at baseline and after each dose of Gardasil in each and any group.
-
To describe the humoral immune response to the CYD dengue vaccine at baseline and after each dose of the CYD dengue vaccine in each and any group.
-
To describe the safety of Gardasil and the CYD dengue vaccine after each and any dose in each group.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Detailed Description
Participants received 3 doses of CYD dengue vaccine and 2 doses of Gardasil administered either concomitantly or sequentially.
The study activities were put on hold for several months (up to 6 months for some participants) to obtain the approval of Protocol Amendment 1 by the competent authorities and completed the associated logistic tasks. Due to this protocol amendment as per Independent Data Monitoring Committee recommendation, only previously dengue immune participants (seropositive for dengue before vaccination) were eligible to complete the vaccination schedule. Dengue non-immune participants (seronegative for dengue before vaccination) did not receive any additional CYD dengue vaccine injections, but were followed for safety up to 6 months after the last injection.
Due to the change in amendment 1, the number of evaluable dengue immune participants at baseline did not meet the predefined number of participants that would have allowed for a global power of at least 80% for non-inferiority testing of Gardasil vaccine and CYD dengue vaccine (121 per group for the co-primary objectives and 194 per group for the secondary objectives).
All participants were assessed for immunogenicity and safety. Safety assessments included solicited reactions within 7 or 14 days after each injection, unsolicited adverse events (AEs) within 28 days after each injection, non-serious AEs of Special Interests (AESIs) within 7 days after each injection, and serious adverse events including AESI and hospitalized virologically-confirmed dengue cases during the study period.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CYD Dengue Vaccine + Gardasil (Concomitant Administration) Dengue immune participants 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 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. |
Biological: CYD Dengue Vaccine
0.5 mL, SC injection at Day 0, Month 6 and 12, respectively.
Other Names:
Biological: Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.
0.5 mL, IM injection at Day 0 and Month 6, respectively.
Other Names:
|
| Experimental: CYD Dengue Vaccine + Gardasil (Sequential Administration) 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. |
Biological: CYD Dengue Vaccine
0.5 mL, SC injection at Month 1, 7 and 13, respectively.
Other Names:
Biological: Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.
0.5 mL, IM injection at Day 0 and Month 6, respectively.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 [28 days after the last Gardasil vaccination]
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.
- Geometric Mean Titers Against Each Parental Dengue Virus Serotype 28 Days After Third CYD Dengue Vaccination in the Previously Dengue Immune Participants [28 days after third CYD dengue vaccination]
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.
Secondary Outcome Measures
- 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 [28 days after the last Gardasil vaccination]
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.
- 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 [Day 0 (pre-vaccination) and 28 days after Gardasil vaccination 1 and 2]
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.
- 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 [Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination]
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.
- 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 [Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination]
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 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 [Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination]
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.
- Number of Participants Reporting Immediate Adverse Events (AEs) Following Vaccination With Gardasil or CYD Dengue Vaccine [Within 30 minutes after any and each vaccination]
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.
- Number of Participants Reporting Solicited Injection Site Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine [Up to 7 days after any and each vaccination]
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.
- Number of Participants Reporting Solicited Systemic Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine [Up to 14 days after any and each vaccination]
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.
- Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With Gardasil or CYD Dengue Vaccine [Up to 28 days after any and each vaccination]
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.
- Number of Participants Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Gardasil or CYD Dengue Vaccine [Within 7 days after any and each vaccination]
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.
- Number of Participants Reporting Serious Adverse Events (SAEs) Including Serious Adverse Event of Special Interests Following Vaccination With Gardasil or CYD Dengue Vaccine [From Day 0 up to 6 months after the last Gardasil or CYD vaccination]
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.
- Number of Participants Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Gardasil or CYD Dengue Vaccine [From Day 0 up to 6 months after the last Gardasil or CYD vaccination]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Participants aged 9 to 13 years (i.e., from the day of the 9th birthday to the day prior to the 14th birthday) on the day of inclusion.
-
Informed consent form (ICF) or Assent form (AF) had been signed and dated by the participant (based on local regulations), and/or ICF had been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations).
-
Participant (or participant and parent[s] or another legally acceptable representative) was (were) able to attend all scheduled visits and complied with all trial procedures.
-
Participant in good health, based on medical history, and physical examination.
Exclusion Criteria:
-
Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female had to be pre-menarche, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination).
-
Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
-
Planned receipt of any vaccine in the 4 weeks following any trial vaccination.
-
Previous vaccination against dengue disease with the trial vaccine.
-
Previous vaccination against human papillomavirus (HPV) disease with either the trial vaccine or another vaccine.
-
Receipt of immune globulins, blood or blood-derived products in the past 3 months.
-
Known or suspected congenital or acquired immunodeficiency (including human immunodeficiency virus infection with impaired immune function); or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
-
History of HPV infection, confirmed either clinically, serologically, or microbiologically as reported by participant or parent(s) or another legally acceptable representative.
-
Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances.
-
Thrombocytopenia, contraindicating IM vaccination.
-
Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination.
-
Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
-
Current alcohol abuse or drug addiction that, based on investigator's judgment, might interfered with the participant's ability to comply with trial procedures.
-
Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfered with trial conduct or completion.
-
Identified as an Investigator or employee of the Investigator with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
-
Self-reported Hepatitis B, Hepatitis C infection.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Sanofi Pasteur Investigational Site 004 | Klang | Malaysia | 42000 | |
| 2 | Sanofi Pasteur Investigational Site 005 | Kuala Lumpur | Malaysia | 50590 | |
| 3 | Sanofi Pasteur Investigational Site 001 | Kuala Lumpur | Malaysia | 59100 | |
| 4 | Sanofi Pasteur Investigational Site 003 | Kuantan | Malaysia | 25100 | |
| 5 | Sanofi Pasteur Investigational Site 002 | Sibu | Malaysia | 96000 |
Sponsors and Collaborators
- Sanofi Pasteur, a Sanofi Company
Investigators
- Study Director: Medical Director, Sanofi Pasteur SA
Study Documents (Full-Text)
More Information
Publications
None provided.- CYD67
- U1111-1161-3376
- 2019-003135-36
Study Results
Participant Flow
| 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 Detail | 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) |
|---|---|---|
| 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) | 263 | 260 |
| COMPLETED | 102 | 84 |
| NOT COMPLETED | 164 | 178 |
Baseline Characteristics
| Arm/Group Title | CYD Dengue Vaccine + Gardasil (Concomitant Administration) | CYD Dengue Vaccine + Gardasil (Sequential Administration) | Total |
|---|---|---|---|
| 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 Participants | 266 | 262 | 528 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
10.4
(1.20)
|
10.5
(1.18)
|
10.4
(1.19)
|
| Sex: Female, Male (Count of 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 (Count of Participants) | |||
| Count of Participants [Participants] |
0
0%
|
||
| Dengue Seropositivity Status (Count of Participants) | |||
| Dengue immune |
109
41%
|
88
33.6%
|
197
37.3%
|
| Dengue non-immune |
157
59%
|
174
66.4%
|
331
62.7%
|
Outcome Measures
| 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 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 104 | 86 |
| HPV-6 |
420
|
428
|
| HPV-11 |
1288
|
1601
|
| HPV-16 |
6221
|
7629
|
| HPV-18 |
829
|
1042
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMT ratio |
| Estimated Value | 0.982 | |
| Confidence Interval |
(2-Sided) 95% 0.664 to 1.45 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMT ratio |
| Estimated Value | 0.804 | |
| Confidence Interval |
(2-Sided) 95% 0.626 to 1.03 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMT ratio |
| Estimated Value | 0.815 | |
| Confidence Interval |
(2-Sided) 95% 0.608 to 1.09 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMT ratio |
| Estimated Value | 0.795 | |
| Confidence Interval |
(2-Sided) 95% 0.603 to 1.05 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Geometric Mean Titers Against Each Parental Dengue Virus Serotype 28 Days After Third CYD Dengue Vaccination in the Previously Dengue Immune Participants |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 102 | 84 |
| Serotype 1 |
447
|
453
|
| Serotype 2 |
561
|
717
|
| Serotype 3 |
460
|
549
|
| Serotype 4 |
323
|
303
|
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMT ratio |
| Estimated Value | 0.987 | |
| Confidence Interval |
(2-Sided) 95% 0.574 to 1.70 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMT ratio |
| Estimated Value | 0.783 | |
| Confidence Interval |
(2-Sided) 95% 0.500 to 1.22 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMT ratio |
| Estimated Value | 0.836 | |
| Confidence Interval |
(2-Sided) 95% 0.568 to 1.23 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
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 | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | GMT ratio |
| Estimated Value | 1.07 | |
| Confidence Interval |
(2-Sided) 95% 0.813 to 1.40 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 103 | 81 |
| HPV-6 |
98.1
36.9%
|
100.0
38.2%
|
| HPV-11 |
100.0
37.6%
|
100.0
38.2%
|
| HPV-16 |
100.0
37.6%
|
100.0
38.2%
|
| HPV-18 |
100.0
37.6%
|
100.0
38.2%
|
| 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 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 109 | 88 |
| HPV-6: Day 0 |
5.70
|
5.61
|
| HPV-6: 28 days post vaccination 1 |
54.9
|
61.8
|
| HPV-6: 28 days post vaccination 2 |
420
|
428
|
| HPV-11: Day 0 |
4.16
|
4.00
|
| HPV-11: 28 days post vaccination 1 |
58.1
|
78.5
|
| HPV-11: 28 days post vaccination 2 |
1288
|
1601
|
| HPV-16: Day 0 |
5.62
|
5.50
|
| HPV-16: 28 days post vaccination 1 |
148
|
150
|
| HPV-16: 28 days post vaccination 2 |
6221
|
7629
|
| HPV-18: Day 0 |
5.26
|
5.06
|
| HPV-18: 28 days post vaccination 1 |
23.5
|
31.6
|
| HPV-18: 28 days post vaccination 2 |
829
|
1042
|
| 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 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 109 | 88 |
| Serotype 1: Day 0 |
62.3
|
81.5
|
| Serotype 1: 28 days post vaccination 1 |
382
|
449
|
| Serotype 1: 28 days post vaccination 2 |
403
|
529
|
| Serotype 1: 28 days post vaccination 3 |
447
|
453
|
| Serotype 2: Day 0 |
110
|
130
|
| Serotype 2: 28 days post-vaccination 1 |
750
|
848
|
| Serotype 2: 28 days post-vaccination 2 |
728
|
937
|
| Serotype 2: 28 days post-vaccination 3 |
561
|
717
|
| Serotype 3: Day 0 |
72.3
|
96.7
|
| Serotype 3: 28 days post-vaccination 1 |
432
|
517
|
| Serotype 3: 28 days post-vaccination 2 |
389
|
543
|
| Serotype 3: 28 days post-vaccination 3 |
460
|
549
|
| Serotype 4: Day 0 |
26.3
|
23.7
|
| Serotype 4: 28 days post-vaccination 1 |
330
|
286
|
| Serotype 4: 28 days post-vaccination 2 |
284
|
282
|
| Serotype 4: 28 days post-vaccination 3 |
323
|
303
|
| 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 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 109 | 88 |
| Serotype 1: Day 0 |
66.1
24.8%
|
72.7
27.7%
|
| Serotype 1: 28 days post vaccination 1 |
91.6
34.4%
|
90.9
34.7%
|
| Serotype 1: 28 days post vaccination 2 |
96.2
36.2%
|
95.4
36.4%
|
| Serotype 1: 28 days post vaccination 3 |
95.1
35.8%
|
100.0
38.2%
|
| Serotype 2: Day 0 |
83.5
31.4%
|
81.8
31.2%
|
| Serotype 2: 28 days post-vaccination 1 |
93.5
35.2%
|
92.0
35.1%
|
| Serotype 2: 28 days post-vaccination 2 |
99.0
37.2%
|
97.7
37.3%
|
| Serotype 2: 28 days post-vaccination 3 |
97.1
36.5%
|
98.8
37.7%
|
| Serotype 3: Day 0 |
89.0
33.5%
|
86.2
32.9%
|
| Serotype 3: 28 days post-vaccination 1 |
96.2
36.2%
|
97.7
37.3%
|
| Serotype 3: 28 days post-vaccination 2 |
100.0
37.6%
|
100.0
38.2%
|
| Serotype 3: 28 days post-vaccination 3 |
99.0
37.2%
|
100.0
38.2%
|
| Serotype 4: Day 0 |
59.6
22.4%
|
54.5
20.8%
|
| Serotype 4: 28 days post-vaccination 1 |
93.5
35.2%
|
98.9
37.7%
|
| Serotype 4: 28 days post-vaccination 2 |
100.0
37.6%
|
100.0
38.2%
|
| Serotype 4: 28 days post-vaccination 3 |
100.0
37.6%
|
100.0
38.2%
|
| 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 |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 109 | 88 |
| At least 1 Serotype: Day 0: >=10 (1/dil) |
100.0
37.6%
|
100.0
38.2%
|
| At least 1 Serotype: Day 0: >=100 (1/dil) |
90.8
34.1%
|
88.6
33.8%
|
| At least 1 Serotype:post vaccination 1:>=10(1/dil) |
97.2
36.5%
|
100.0
38.2%
|
| At least 1 Serotype:post vaccination1:>=100(1/dil) |
95.3
35.8%
|
96.6
36.9%
|
| At least 1 Serotype:post vaccination 2:>=10(1/dil) |
100.0
37.6%
|
100.0
38.2%
|
| At least 1 Serotype:post vaccination2:>=100(1/dil) |
96.2
36.2%
|
98.9
37.7%
|
| At least 1 Serotype:post vaccination 3:>=10(1/dil) |
100.0
37.6%
|
100.0
38.2%
|
| At least 1 Serotype:post vaccination3:>=100(1/dil) |
98.0
36.8%
|
97.6
37.3%
|
| At least 2 Serotypes: Day 0: >=10 (1/dil) |
84.4
31.7%
|
81.8
31.2%
|
| At least 2 Serotypes: Day 0: >=100 (1/dil) |
34.9
13.1%
|
39.8
15.2%
|
| At least 2 Serotypes:post vaccination1:>=10(1/dil) |
94.4
35.5%
|
97.7
37.3%
|
| At least 2Serotypes:post vaccination1:>=100(1/dil) |
85.0
32%
|
80.7
30.8%
|
| At least 2 Serotypes:post vaccination2:>=10(1/dil) |
100.0
37.6%
|
100.0
38.2%
|
| At least 2Serotypes:post vaccination2:>=100(1/dil) |
84.6
31.8%
|
92.0
35.1%
|
| At least 2 Serotypes:post vaccination3:>=10(1/dil) |
100.0
37.6%
|
100.0
38.2%
|
| At least 2Serotypes:post vaccination3:>=100(1/dil) |
93.1
35%
|
94.0
35.9%
|
| At least 3 Serotypes:Day 0: >=10 (1/dil) |
71.6
26.9%
|
69.3
26.5%
|
| At least 3 Serotypes:Day 0: >=100 (1/dil) |
23.9
9%
|
27.3
10.4%
|
| At least 3 Serotypes:post vaccination1:>=10(1/dil) |
92.5
34.8%
|
92.0
35.1%
|
| At least 3Serotypes:post vaccination1:>=100(1/dil) |
75.7
28.5%
|
73.9
28.2%
|
| At least 3 Serotypes:post vaccination2:>=10(1/dil) |
99.0
37.2%
|
98.9
37.7%
|
| At least 3Serotypes:post vaccination2:>=100(1/dil) |
77.9
29.3%
|
86.2
32.9%
|
| At least 3 Serotypes:post vaccination3:>=10(1/dil) |
97.1
36.5%
|
100.0
38.2%
|
| At least 3Serotypes:post vaccination3:>=100(1/dil) |
83.3
31.3%
|
88.1
33.6%
|
| At least 4 Serotypes:Day 0: >=10 (1/dil) |
42.2
15.9%
|
43.7
16.7%
|
| At least 4 Serotypes:Day 0: >=100 (1/dil) |
6.4
2.4%
|
12.6
4.8%
|
| At least 4 Serotypes:post vaccination1:>=10(1/dil) |
90.6
34.1%
|
89.8
34.3%
|
| At least 4Serotypes:post vaccination1:>=100(1/dil) |
60.4
22.7%
|
62.5
23.9%
|
| At least 4 Serotypes:post vaccination2:>=10(1/dil) |
96.2
36.2%
|
94.3
36%
|
| At least 4Serotypes:post vaccination2:>=100(1/dil) |
67.3
25.3%
|
75.9
29%
|
| At least 4 Serotypes:post vaccination3:>=10(1/dil) |
94.1
35.4%
|
98.8
37.7%
|
| At least 4Serotypes:post vaccination3:>=100(1/dil) |
72.5
27.3%
|
77.4
29.5%
|
| Title | Number of Participants Reporting Immediate Adverse Events (AEs) Following Vaccination With Gardasil or CYD Dengue Vaccine |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 263 | 260 |
| Post any vaccination |
0
0%
|
3
1.1%
|
| Post vaccination 1 (Visit 1) |
0
0%
|
1
0.4%
|
| Post CYD vaccination 1 (Visit 2) |
1
0.4%
|
|
| Post vaccination 2 (Visit 4) |
0
0%
|
0
0%
|
| Post CYD vaccination 2 (Visit 5) |
1
0.4%
|
|
| Post CYD vaccination 3 (Visit 7) |
0
0%
|
0
0%
|
| Title | Number of Participants Reporting Solicited Injection Site Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 263 | 260 |
| Pain: Post any CYD/Gardasil vaccine |
206
77.4%
|
193
73.7%
|
| Pain: Post CYD/Gardasil vaccination 1 |
163
61.3%
|
157
59.9%
|
| Pain: Post CYD/Gardasil vaccination 2 |
151
56.8%
|
141
53.8%
|
| Pain: Post CYD vaccination 3 |
33
12.4%
|
24
9.2%
|
| Erythema: Post any CYD/Gardasil vaccine |
45
16.9%
|
38
14.5%
|
| Erythema: Post CYD/Gardasil vaccination 1 |
30
11.3%
|
29
11.1%
|
| Erythema: Post CYD/Gardasil vaccination 2 |
25
9.4%
|
19
7.3%
|
| Erythema: Post CYD vaccination 3 |
9
3.4%
|
2
0.8%
|
| Swelling: Post any CYD/Gardasil vaccine |
43
16.2%
|
31
11.8%
|
| Swelling: Post CYD/Gardasil vaccination 1 |
22
8.3%
|
22
8.4%
|
| Swelling: Post CYD/Gardasil vaccination 2 |
30
11.3%
|
18
6.9%
|
| Swelling: Post CYD vaccination 3 |
9
3.4%
|
3
1.1%
|
| Title | Number of Participants Reporting Solicited Systemic Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 263 | 260 |
| Fever: Post any vaccination |
36
13.5%
|
47
17.9%
|
| Fever: Post vaccination 1 (Visit 1) |
21
7.9%
|
8
3.1%
|
| Fever: Post CYD vaccination 1 (Visit 2) |
15
5.6%
|
|
| Fever: Post vaccination 2 (Visit 4) |
10
3.8%
|
11
4.2%
|
| Fever: Post CYD vaccination 2 (Visit 5) |
12
4.5%
|
|
| Fever: Post CYD vaccination 3 (Visit 7) |
8
3%
|
6
2.3%
|
| Headache: Post any vaccination |
125
47%
|
146
55.7%
|
| Headache: Post vaccination 1 (Visit 1) |
99
37.2%
|
93
35.5%
|
| Headache: Post CYD vaccination 1 (Visit 2) |
73
27.4%
|
|
| Headache: Post vaccination 2 (Visit 4) |
61
22.9%
|
70
26.7%
|
| Headache: Post CYD vaccination 2 (Visit 5) |
51
19.2%
|
|
| Headache: Post CYD vaccination 3 (Visit 7) |
15
5.6%
|
17
6.5%
|
| Malaise: Post any vaccination |
111
41.7%
|
137
52.3%
|
| Malaise: Post vaccination 1 (Visit 1) |
82
30.8%
|
78
29.8%
|
| Malaise: Post CYD vaccination 1 (Visit 2) |
69
25.9%
|
|
| Malaise: Post vaccination 2 (Visit 4) |
57
21.4%
|
54
20.6%
|
| Malaise: Post CYD vaccination 2 (Visit 5) |
40
15%
|
|
| Malaise: Post CYD vaccination 3 (Visit 7) |
20
7.5%
|
17
6.5%
|
| Myalgia: Post any vaccination |
127
47.7%
|
156
59.5%
|
| Myalgia: Post vaccination 1 (Visit 1) |
93
35%
|
94
35.9%
|
| Myalgia: Post CYD vaccination 1 (Visit 2) |
63
23.7%
|
|
| Myalgia: Post vaccination 2 (Visit 4) |
72
27.1%
|
70
26.7%
|
| Myalgia: Post CYD vaccination 2 (Visit 5) |
43
16.2%
|
|
| Myalgia: Post CYD vaccination 3 (Visit 7) |
16
6%
|
13
5%
|
| Asthenia: Post any vaccination |
133
50%
|
132
50.4%
|
| Asthenia: Post vaccination 1 (Visit 1) |
101
38%
|
89
34%
|
| Asthenia: Post CYD vaccination 1 (Visit 2) |
63
23.7%
|
|
| Asthenia: Post vaccination 2 (Visit 4) |
74
27.8%
|
46
17.6%
|
| Asthenia: Post CYD vaccination 2 (Visit 5) |
35
13.2%
|
|
| Asthenia: Post CYD vaccination 3 (Visit 7) |
19
7.1%
|
16
6.1%
|
| Title | Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With Gardasil or CYD Dengue Vaccine |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 263 | 260 |
| Post any vaccination |
54
20.3%
|
91
34.7%
|
| Post vaccination 1 (Visit 1) |
34
12.8%
|
38
14.5%
|
| Post CYD vaccination 1 (Visit 2) |
38
14.3%
|
|
| Post vaccination 2 (Visit 4) |
24
9%
|
22
8.4%
|
| Post CYD vaccination 2 (Visit 5) |
28
10.5%
|
|
| Post CYD vaccination 3 (Visit 7) |
5
1.9%
|
7
2.7%
|
| Title | Number of Participants Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Gardasil or CYD Dengue Vaccine |
|---|---|
| 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 |
Outcome Measure Data
| 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) |
|---|---|---|
| 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. |
| Measure Participants | 263 | 260 |
| Post any vaccination |
0
0%
|
0
0%
|
| Post vaccination 1 (Visit 1) |
0
0%
|
0
0%
|
| Post CYD vaccination 1 (Visit 2) |
0
0%
|
|
| Post vaccination 2 (Visit 4) |
0
0%
|
0
0%
|
| Post CYD vaccination 2 (Visit 5) |
0
0%
|
|
| Post CYD vaccination 3 (Visit 7) |
0
0%
|
0
0%
|
| Title | Number of Participants Reporting Serious Adverse Events (SAEs) Including Serious Adverse Event of Special Interests Following Vaccination With Gardasil or CYD Dengue Vaccine |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on SafAS. |
| Arm/Group Title | CYD Dengue Vaccine + Gardasil (Concomitant Administration) | CYD Dengue Vaccine + Gardasil (Sequential Administration) |
|---|---|---|
| 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. |
| Measure Participants | 263 | 260 |
| SAE |
11
4.1%
|
8
3.1%
|
| Serious AESI |
1
0.4%
|
2
0.8%
|
| Title | Number of Participants Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Gardasil or CYD Dengue Vaccine |
|---|---|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was performed on SafAS. |
| Arm/Group Title | CYD Dengue Vaccine + Gardasil (Concomitant Administration) | CYD Dengue Vaccine + Gardasil (Sequential Administration) |
|---|---|---|
| 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. |
| Measure Participants | 263 | 260 |
| Count of Participants [Participants] |
1
0.4%
|
1
0.4%
|
Adverse Events
| 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) | ||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/263 (0%) | 0/260 (0%) | ||
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 (4.2%) | 8/260 (3.1%) | ||
| Infections and infestations | ||||
| Appendicitis | 1/263 (0.4%) | 1 | 1/260 (0.4%) | 1 |
| Chikungunya Virus Infection | 1/263 (0.4%) | 1 | 0/260 (0%) | 0 |
| Dengue Fever | 1/263 (0.4%) | 1 | 2/260 (0.8%) | 2 |
| Gastroenteritis | 1/263 (0.4%) | 1 | 0/260 (0%) | 0 |
| Gingival Abscess | 0/263 (0%) | 0 | 1/260 (0.4%) | 1 |
| Influenza | 1/263 (0.4%) | 1 | 0/260 (0%) | 0 |
| Pneumonia Mycoplasmal | 1/263 (0.4%) | 1 | 0/260 (0%) | 0 |
| Tonsillitis | 1/263 (0.4%) | 1 | 0/260 (0%) | 0 |
| Viral Infection | 1/263 (0.4%) | 1 | 0/260 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||
| Fall | 0/263 (0%) | 0 | 1/260 (0.4%) | 1 |
| Sports Injury | 0/263 (0%) | 0 | 2/260 (0.8%) | 2 |
| Tendon Rupture | 1/263 (0.4%) | 1 | 0/260 (0%) | 0 |
| Renal and urinary disorders | ||||
| Glomerulonephritis Acute | 1/263 (0.4%) | 1 | 0/260 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Asthma | 2/263 (0.8%) | 2 | 1/260 (0.4%) | 1 |
| Tonsillar Hypertrophy | 0/263 (0%) | 0 | 1/260 (0.4%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| CYD Dengue Vaccine + Gardasil (Concomitant Administration) | CYD Dengue Vaccine + Gardasil (Sequential Administration) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 233/263 (88.6%) | 235/260 (90.4%) | ||
| General disorders | ||||
| Asthenia | 133/263 (50.6%) | 194 | 132/260 (50.8%) | 249 |
| Injection Site Erythema | 45/263 (17.1%) | 99 | 38/260 (14.6%) | 63 |
| Injection Site Pain | 206/263 (78.3%) | 532 | 193/260 (74.2%) | 452 |
| Injection Site Swelling | 43/263 (16.3%) | 89 | 31/260 (11.9%) | 48 |
| Malaise | 111/263 (42.2%) | 159 | 137/260 (52.7%) | 260 |
| Pyrexia | 39/263 (14.8%) | 43 | 53/260 (20.4%) | 61 |
| Infections and infestations | ||||
| Upper Respiratory Tract Infection | 20/263 (7.6%) | 21 | 30/260 (11.5%) | 37 |
| Musculoskeletal and connective tissue disorders | ||||
| Myalgia | 127/263 (48.3%) | 181 | 156/260 (60%) | 283 |
| Nervous system disorders | ||||
| Headache | 126/263 (47.9%) | 178 | 147/260 (56.5%) | 311 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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
| Name/Title | Trial Transparency Team |
|---|---|
| Organization | Sanofi Pasteur |
| Phone | 800-633-1610 ext 1# |
| Contact-US@sanofi.com |
- CYD67
- U1111-1161-3376
- 2019-003135-36