Immunogenicity and Safety of a Tetravalent Dengue Vaccine... | NCT02993757

NCT02993757

ID	Type	Description	Link
U1111-1161-3376	Other Identifier	WHO
2019-003135-36	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
CYD Dengue Vaccine + Gardasil (Concomitant Administration)	Experimental	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 Biological: Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.
CYD Dengue Vaccine + Gardasil (Sequential Administration)	Experimental	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 Biological: Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
CYD Dengue Vaccine	Biological	0.5 mL, SC injection at Day 0, Month 6 and 12, respectively.	CYD Dengue Vaccine + Gardasil (Concomitant Administration)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	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.	28 days after the last Gardasil vaccination
Geometric Mean Titers Against Each Parental Dengue Virus Serotype 28 Days After Third CYD Dengue Vaccination in the Previously Dengue Immune Participants	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.	28 days after third CYD dengue vaccination

Secondary Outcomes

Measure	Description	Time Frame
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	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.

Eligibility Module

Eligibility 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/Locations Module

Name	Affiliation	Role
Medical Director	Sanofi Pasteur SA	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Sanofi Pasteur Investigational Site 004		Klang		42000	Malaysia
Sanofi Pasteur Investigational Site 005

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
34250977	Derived	Hassan J, Toh TH, Sivapunniam SK, Hasim R, Ghazali NF, Sulaiman S, Koh MT, Meyer S, Toh ML, Zocchetti C, Vigne C, Mascarenas C. Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Quadrivalent Human Papillomavirus Vaccine in Boys and Girls 9-13 Years of Age in Malaysia: A Phase IIIb, Randomized, Open-label Study. Pediatr Infect Dis J. 2021 Aug 1;40(8):774-781. doi: 10.1097/INF.0000000000003164.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jan 5, 2018	May 20, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Analysis was performed on all randomized participants.

Arm/Group Information

ID	Title	Description
BG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
BG001	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.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000266 BG001262 BG002528

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

HPV-6

Title	Measurements
	OG000420(327 to 539) OG001428(314 to 583)

HPV-11

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Antigen HPV-6					GMT ratio	0.982			2-Sided	95	0.664	1.45					Other
OG000 OG001	Antigen HPV-11

Primary

Geometric Mean Titers Against Each Parental Dengue Virus Serotype 28 Days After Third CYD Dengue Vaccination in the Previously Dengue Immune Participants

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.

Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants evaluable and had available data for this outcome measure.

Posted

Geometric Mean

95% Confidence Interval

titer (1/dilution)

28 days after third CYD dengue vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	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.

Secondary

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

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.

Analysis was performed on FAS. Here, 'overall number of participants analyzed' = participants evaluable and had available data for this outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

28 days after the last Gardasil vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001

Secondary

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

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.

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.

Posted

Geometric Mean

95% Confidence Interval

mMU/mL

Day 0 (pre-vaccination) and 28 days after Gardasil vaccination 1 and 2

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	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.

Secondary

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

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.

Posted

Geometric Mean

95% Confidence Interval

titer (1/dilution)

Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	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.

Secondary

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

Posted

Number

95% Confidence Interval

percentage of participants

Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	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.

Secondary

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

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.

Posted

Number

95% Confidence Interval

percentage of participants

Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	CYD Dengue Vaccine + Gardasil (Sequential Administration)

Secondary

Number of Participants Reporting Immediate Adverse Events (AEs) Following Vaccination With Gardasil or CYD Dengue Vaccine

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.

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.

Posted

Count of Participants

Participants

Within 30 minutes after any and each vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	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.

Secondary

Number of Participants Reporting Solicited Injection Site Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine

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.

Analysis was performed on SafAS. Here, 'Number analyzed' = participants with available data for each specified categories.

Posted

Count of Participants

Participants

Up to 7 days after any and each vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	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.

Secondary

Number of Participants Reporting Solicited Systemic Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine

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.

Analysis was performed on SafAS. Here, 'Number analyzed' = participants with available data for each specified categories.

Posted

Count of Participants

Participants

Up to 14 days after any and each vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	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.

Secondary

Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With Gardasil or CYD Dengue Vaccine

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.

Analysis was performed on SafAS. Here, 'Number analyzed' = participants with available data for each specified categories.

Posted

Count of Participants

Participants

Up to 28 days after any and each vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	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.

Secondary

Number of Participants Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Gardasil or CYD Dengue Vaccine

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.

Analysis was performed on SafAS. Here, 'Number analyzed' = participants with available data for each specified categories.

Posted

Count of Participants

Participants

Within 7 days after any and each vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	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.

Secondary

Number of Participants Reporting Serious Adverse Events (SAEs) Including Serious Adverse Event of Special Interests Following Vaccination With Gardasil or CYD Dengue Vaccine

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.

Analysis was performed on SafAS.

Posted

Count of Participants

Participants

From Day 0 up to 6 months after the last Gardasil or CYD vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	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.

Secondary

Number of Participants Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Gardasil or CYD Dengue Vaccine

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.

Analysis was performed on SafAS.

Posted

Count of Participants

Participants

From Day 0 up to 6 months after the last Gardasil or CYD vaccination

ID	Title	Description
OG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.
OG001	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	CYD Dengue Vaccine + Gardasil (Concomitant Administration)	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.	0	263	11	263	233	263
EG001	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.	0	260	8	260	235	260

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Appendicitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected263 at risk EG0011 events1 affected260 at risk
Chikungunya Virus Infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected263 at risk EG0010 events0 affected260 at risk
Dengue Fever	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected263 at risk EG0012 events2 affected260 at risk
Gastroenteritis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected263 at risk EG0010 events0 affected260 at risk
Gingival Abscess	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected263 at risk EG0011 events1 affected260 at risk
Influenza	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected263 at risk EG0010 events0 affected260 at risk
Pneumonia Mycoplasmal	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected263 at risk EG0010 events0 affected260 at risk
Tonsillitis	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected263 at risk EG0010 events0 affected260 at risk
Viral Infection	Infections and infestations	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected263 at risk EG0010 events0 affected260 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected263 at risk EG0011 events1 affected260 at risk
Sports Injury	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected263 at risk EG0012 events2 affected260 at risk
Tendon Rupture	Injury, poisoning and procedural complications	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected263 at risk EG0010 events0 affected260 at risk
Glomerulonephritis Acute	Renal and urinary disorders	MedDRA 19.0	Systematic Assessment	EG0001 events1 affected263 at risk EG0010 events0 affected260 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0002 events2 affected263 at risk EG0011 events1 affected260 at risk
Tonsillar Hypertrophy	Respiratory, thoracic and mediastinal disorders	MedDRA 19.0	Systematic Assessment	EG0000 events0 affected263 at risk EG0011 events1 affected260 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Asthenia	General disorders	MedDRA 19.0	Systematic Assessment		EG000194 events133 affected263 at risk EG001249 events132 affected260 at risk
Injection Site Erythema	General disorders	MedDRA 19.0	Systematic Assessment		EG00099 events45 affected263 at risk EG00163 events38 affected260 at risk
Injection Site Pain	General disorders	MedDRA 19.0	Systematic Assessment		EG000532 events206 affected263 at risk EG001452 events193 affected260 at risk
Injection Site Swelling	General disorders	MedDRA 19.0	Systematic Assessment		EG00089 events43 affected263 at risk EG00148 events31 affected260 at risk
Malaise	General disorders	MedDRA 19.0	Systematic Assessment		EG000159 events111 affected263 at risk EG001260 events137 affected260 at risk
Pyrexia	General disorders	MedDRA 19.0	Systematic Assessment	Pyrexia events that occurred after 14 days post-vaccination were considered as unsolicited AE.	EG00043 events39 affected263 at risk EG00161 events53 affected260 at risk
Upper Respiratory Tract Infection	Infections and infestations	MedDRA 19.0	Systematic Assessment		EG00021 events20 affected263 at risk EG00137 events30 affected260 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 19.0	Systematic Assessment		EG000181 events127 affected263 at risk EG001283 events156 affected260 at risk
Headache	Nervous system disorders	MedDRA 19.0	Systematic Assessment	Headache events that occurred after 14 days post-vaccination were considered as unsolicited AE.	EG000178 events126 affected263 at risk EG001311 events147 affected260 at risk

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

ID	Term
D003715	Dengue
D019595	Severe Dengue

Ancestor Terms

ID	Term
D000096724	Mosquito-Borne Diseases
D000079426	Vector Borne Diseases
D007239	Infections
D001102	Arbovirus Infections
D014777	Virus Diseases
D018177	Flavivirus Infections
D018178	Flaviviridae Infections
D012327	RNA Virus Infections
D006482	Hemorrhagic Fevers, Viral

ID	Term
D053059	Dengue Vaccines
D000068857	Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 16, 18

OG0011601(1323 to 1937)

The 95% confidence interval was not computable, since all participants had the same value.

ID	Term
D014765	Viral Vaccines
D014612	Vaccines
D001688	Biological Products
D045424	Complex Mixtures
D017778	Vaccines, Combined
D053918	Papillomavirus Vaccines