Dengue, Dengue Fever, Dengue Hemorrhagic Fever
Conditions
Keywords
Dengue Virus, Dengue fever, Dengue Hemorrhagic Fever, CYD dengue vaccine, Flavivirus, Dengue Disease
Brief summary
The aim of the study was to assess the efficacy of Sanofi Pasteur's CYD dengue vaccine in preventing symptomatic virologically-confirmed dengue cases for dengue-endemic areas of Latin America. Primary Objective: To assess the efficacy of CYD dengue vaccine after 3 vaccinations at 0, 6, and 12 months in preventing symptomatic virologically-confirmed dengue (VCD) cases, regardless of the severity, due to any of the four serotypes in children and adolescents aged 9 to 16 years at the time of inclusion. Secondary Objectives: * To describe the efficacy of CYD dengue vaccine in preventing symptomatic VCD cases after the third dose to the end of the Active Phase, after at least 1 dose, and after 2 doses. * To describe the occurrence of hospitalized VCD cases and the occurrence of severe (clinically severe or as per World Health Organization (WHO) criteria) VCD cases, throughout the Surveillance Expansion Period (SEP) and throughout the trial (from Day 0 until the end of the study). * To describe the antibody response to each dengue serotype after Dose 2, after Dose 3, and 1 and 5 years after Dose 3. * To describe the occurrence of serious adverse events (SAEs), including SAEs of special interest in all participants throughout the trial period.
Detailed description
Participants were randomized to either receive 3 injections of CYD dengue vaccine or a placebo at 0, 6, and 12 months. A subset of participants from each country (N=2000) was also evaluated for reactogenicity and immunogenicity. For each participant, the Active Phase of dengue case detection began after the first injection (Dose 1) and continued until 13 months after the third injection (Dose 3). It was assumed that 12 months of surveillance should result in the detection of a sufficient number of VCD cases to allow for an assessment of efficacy. The Hospital Phase began after the Active Phase. Participants with a febrile illness and requiring hospitalization were screened for dengue until the end of the study. Participants who consented to participate in the SEP were actively followed for dengue case detection (i.e. at least weekly contact and capturing any acute febrile illness, not just hospitalized febrile cases, as in the Active Phase). The SEP was designed to maximize the detection of symptomatic VCD (hospitalized or not) in order to describe CYD dengue vaccine efficacy and safety in preventing symptomatic dengue in the long-term. Participants who declined participating in the SEP continued surveillance as in the Hospital Phase until trial completion. Symptomatic VCD cases occurring more than (\>) 28 days after dose 3 (during the Active Phase) are defined as: * Acute febrile illness (i.e. temperature \>=38 degree Celsius (°C) on at least 2 consecutive days) * Virologically confirmed by dengue Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and/or dengue non-structural (NS)1 enzyme-linked immunosorbent assay (ELISA) Ag test. Severity was assessed using a definition consistent with the 1997 WHO Classification Dengue Hemorrhagic Fever and by an independent Data Monitoring Committee (IDMC) severity criteria.
Interventions
0.5 mL, Subcutaneous
BIOLOGICALPlacebo: (NaCl) 0.9% solution
0.5 mL, Subcutaneous
Sponsors
Sanofi Pasteur, a Sanofi Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
9 Years to 16 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 9 to 16 years on the day of inclusion and resident of the site zone * Participant in good health, based on medical history and physical examination * Assent form or informed consent form has been signed and dated by the participant (based on local regulations), and informed consent form has been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations) * Participant was able to attend all scheduled visits and comply with all trial procedures.
Exclusion criteria
* Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination). * Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination * Planned participation in another clinical trial during the present trial period * Self-reported or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroids therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) * Self-reported seropositivity for Human Immunodeficiency Virus (HIV) infection * Self-reported systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances * Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion * Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response * Planned receipt of any vaccine in the 4 weeks following any trial vaccination * Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily * Current alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures * Identified as a site employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as a family member (i.e., immediate, husband, wife and their children, adopted or natural) of the site employees or the Investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection With Either CYD Dengue Vaccine or a Placebo | 28 days and up to 13 months post-injection 3 | Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue reverse transcriptase polymerase chain reaction (RT-PCR) and/or dengue non-structural (NS) protein 1 antigen enzyme-linked immunosorbent assay (ELISA). Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Symptomatic VCD Cases Due to Any Serotype Occurring 28 Days Post-dose 1 Following Injection With Either CYD Dengue Vaccine or a Placebo | 28 days post-injection 1 and up to 13 months post-injection 3 | Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group. |
| Number of Symptomatic VCD Cases Due to Any Serotype Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo | 28 days post-injection 2 and up to 13 months post-injection 3 | Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group. |
| Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Day 0 to the end of study (up to 72 months) | Dengue hemorrhagic fever (DHF) cases were defined as number of participants with at least one symptomatic VCD episode meeting the 1997 WHO criteria. (a) Fever: acute onset, high (\>= 38°C) and continuous, lasting 2 to 7 days and (b) any of the pre-listed hemorrhagic manifestations and laboratory findings of thrombocytopenia (platelet \<=100 x 109/L) and plasma leakage as shown by hemoconcentration (hematocrit increased by 20% or more) or pleural effusion (seen on CXR) and/or ascites and/ or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish a clinical diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhage. |
| Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months) | The 1997 WHO criteria are: a) Fever: acute onset, high (\>= 38°C) and continuous, for 2 to 7 days and (b) any of the following: thrombocytopenia (platelet \<=100 x 109/L) and plasma leakage as shown by hematocrit increased by 20% or more or pleural effusion and/or ascites and/or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participant, usually in the form of skin and/or other hemorrhages; Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness; and Grade IV: Profound shock with undetectable blood pressure and pulse. |
| Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Day 0 up to the end of study (up to 72 months) | Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature \>=38°C on at least 2 consecutive days) requiring hospitalization. |
| Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | From consent to participate in the Surveillance Expansion Period to end of the study (up to 72 months) | Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature \>=38°C on at least 2 consecutive days) requiring hospitalization. |
| Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase Following Injection With Either CYD Dengue Vaccine or a Placebo | Day 0 up to 13 months post-injection 3 | Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group. |
| Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months) | The severity of VCD cases was assessed by an IDMC based on a medical review of cases and any of the following criteria:-1) Platelet count \<=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure \<= 20 mmHg in a child, or hypotension \[\<= 90 mmHg\] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. Unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by GCS score 5) Liver impairment (AST \>1000 IU/L or PT INR \>1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine \>= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes. |
| Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Pre-injection 1, 28 days post Injections 2 and 3, 13 months (Visit [V] 07) and 60 months (Visit [V] 12) post-injection 3 | Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (parental strains) were measured by the plaque reduction neutralization test in a pre-defined subset of participants. |
| Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Pre-injection 1, 28 days post Injections 2 and 3, 13 months (V 07) and 60 months (V 12) post-injection 3 | Geometric mean titers for each of the 4 dengue virus serotypes (parental strains) were assessed using the plaque reduction neutralization test in a pre-defined subset of participants. |
| Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Within 7 days after each and any injection | Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 reactions (9-11 years): Pain: incapacitating, unable to perform usual activities; Erythema and Swelling, \>= 50 mm. Grade 3 Solicited injection site reactions (12-16 years): Pain: significant, prevents daily activity; Erythema and Swelling, \>100 mm. |
| Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Within 14 days after each and any injection | Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Asthenia. Grade 3 reactions: Fever: \>= 39°C; Headache, Malaise, Myalgia, and Asthenia: significant, prevents daily activity. |
| Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Day 0 to the end of study (up to 72 months) | The severity of VCD cases was assessed by an Independent Data monitoring Committee (IDMC) based on a medical review of cases and any of the following criteria:1) Platelet count \<=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure \<= 20 mmHg in a child, or hypotension \[\<= 90 mmHg\] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by Glasgow Coma Scale (GCS) score 5) Liver impairment (AST \>1000 IU/L or prothrombin time \[PT\] International normalized ratio \[INR\] \>1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine \>= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes. |
Countries
Brazil, Colombia, Honduras, Mexico, Puerto Rico
Participant flow
Recruitment details
Study participants were enrolled from 08 June 2011 to 16 March 2012 at 5 clinical centers in Brazil, 9 in Colombia, 1 in Honduras, 5 in Mexico, and 2 in Puerto Rico.
Pre-assignment details
A total of 20869 participants were enrolled and randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| CYD Dengue Vaccine Group Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months). | 13,920 |
| Placebo Group Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months). | 6,949 |
| Total | 20,869 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Surveillance Expansion Period | Lost to Follow-up | 73 | 45 |
| Surveillance Expansion Period | Protocol Violation | 386 | 217 |
| Surveillance Expansion Period | Serious adverse event | 20 | 5 |
| Surveillance Expansion Period | Withdrawal by Subject | 1,870 | 986 |
| Vaccination Phase (Up to 25 Months) | Adverse Event | 3 | 0 |
| Vaccination Phase (Up to 25 Months) | Lost to Follow-up | 106 | 46 |
| Vaccination Phase (Up to 25 Months) | Protocol Violation | 43 | 14 |
| Vaccination Phase (Up to 25 Months) | Serious adverse event | 7 | 9 |
| Vaccination Phase (Up to 25 Months) | Withdrawal by Subject | 480 | 240 |
Baseline characteristics
| Characteristic | CYD Dengue Vaccine Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 13920 Participants | 6949 Participants | 20869 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous Age Continuous | 12.5 Years STANDARD_DEVIATION 2.14 | 12.5 Years STANDARD_DEVIATION 2.13 | 12.5 Years STANDARD_DEVIATION 2.14 |
| Region of Enrollment Brazil | 2370 Participants | 1178 Participants | 3548 Participants |
| Region of Enrollment Colombia | 6497 Participants | 3246 Participants | 9743 Participants |
| Region of Enrollment Honduras | 1866 Participants | 933 Participants | 2799 Participants |
| Region of Enrollment Mexico | 2312 Participants | 1152 Participants | 3464 Participants |
| Region of Enrollment Puerto Rico | 875 Participants | 440 Participants | 1315 Participants |
| Sex: Female, Male Female | 7048 Participants | 3532 Participants | 10580 Participants |
| Sex: Female, Male Male | 6872 Participants | 3417 Participants | 10289 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 42 / 13,915 | 27 / 6,939 |
| other Total, other adverse events | 1,038 / 1,333 | 515 / 664 |
| serious Total, serious adverse events | 1,765 / 13,915 | 911 / 6,939 |
Outcome results
Primary
Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection With Either CYD Dengue Vaccine or a Placebo
Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue reverse transcriptase polymerase chain reaction (RT-PCR) and/or dengue non-structural (NS) protein 1 antigen enzyme-linked immunosorbent assay (ELISA). Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time frame: 28 days and up to 13 months post-injection 3
Population: Number of symptomatic VCD cases were assessed in the Per-Protocol Analysis Set for Efficacy, defined as participants who had no protocol deviations.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYD Dengue Vaccine Group | Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection With Either CYD Dengue Vaccine or a Placebo | 176 Cases |
| Placebo Group | Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection With Either CYD Dengue Vaccine or a Placebo | 221 Cases |
Comparison: The statistical methodology was based on the use of the two-sided 95% confidence interval (CI) of the vaccine efficacy (expressed in %). The CI was calculated using the exact method conditional on the total number of cases in both groups (exact method by Breslow \& Day). The vaccine efficacy of the CYD dengue vaccine was considered significant if the lower bound of its 95% CI was greater than 25%.95% CI: [52, 68]
Secondary
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo
Geometric mean titers for each of the 4 dengue virus serotypes (parental strains) were assessed using the plaque reduction neutralization test in a pre-defined subset of participants.
Time frame: Pre-injection 1, 28 days post Injections 2 and 3, 13 months (V 07) and 60 months (V 12) post-injection 3
Population: Antibody titers against each dengue virus serotype strain were assessed in FASI, which included a subset of participants who received at least one dose of vaccine and had a blood sample drawn and result available after the dose. Here,'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Pre-Inj. 1 | 128 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Post Inj. 2 | 458 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Post Inj. 3 | 395 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Year 1 Post Inj. 3 (V 07) | 266 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Year 5 Post Inj. 3 (V 12) | 284 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Pre-Inj. 1 | 138 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Post Inj. 2 | 622 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Post Inj. 3 | 574 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Year 1 Post-Inj. 3 (V 07) | 371 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Year 5 Post-Inj. 3 (V 12) | 297 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Pre-Inj. 1 | 121 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Post Inj. 2 | 556 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Post Inj. 3 | 508 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Year 1 Post Inj. 3 (V 07) | 292 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Year 5 Post Inj. 3 (V 12) | 346 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Pre Inj. 1 | 43.6 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Post Inj. 2 | 261 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Post Inj. 3 | 241 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Year 1 Post Inj. 3 (V 07) | 174 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Year 5 Post Inj. 3 (V 12) | 144 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Post Inj. 3 | 44.3 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Pre-Inj. 1 | 119 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Pre-Inj. 1 | 114 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Post Inj. 2 | 128 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Pre Inj. 1 | 39.0 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Post Inj. 3 | 121 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Post Inj. 2 | 117 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Year 1 Post Inj. 3 (V 07) | 146 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Year 5 Post Inj. 3 (V 12) | 73.6 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Year 5 Post Inj. 3 (V 12) | 210 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Post Inj. 3 | 124 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Pre-Inj. 1 | 115 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Post Inj. 2 | 40.9 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Post Inj. 2 | 124 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Year 1 Post Inj. 3 (V 07) | 137 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Post Inj. 3 | 129 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Year 1 Post Inj. 3 (V 07) | 51.5 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Year 1 Post-Inj. 3 (V 07) | 145 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Year 5 Post Inj. 3 (V 12) | 224 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Year 5 Post-Inj. 3 (V 12) | 201 Titers (1/dilution) |
Secondary
Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
The severity of VCD cases was assessed by an IDMC based on a medical review of cases and any of the following criteria:-1) Platelet count \<=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure \<= 20 mmHg in a child, or hypotension \[\<= 90 mmHg\] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. Unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by GCS score 5) Liver impairment (AST \>1000 IU/L or PT INR \>1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine \>= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.
Time frame: From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)
Population: Number of clinically severe VCD cases were assessed in the Full Analysis Set for Surveillance Expansion Period. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYD Dengue Vaccine Group | Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | 42 Cases |
| Placebo Group | Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | 34 Cases |
Secondary
Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
The severity of VCD cases was assessed by an Independent Data monitoring Committee (IDMC) based on a medical review of cases and any of the following criteria:1) Platelet count \<=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure \<= 20 mmHg in a child, or hypotension \[\<= 90 mmHg\] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by Glasgow Coma Scale (GCS) score 5) Liver impairment (AST \>1000 IU/L or prothrombin time \[PT\] International normalized ratio \[INR\] \>1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine \>= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.
Time frame: Day 0 to the end of study (up to 72 months)
Population: Number of clinically severe VCD cases were assessed in the Safety Analysis Set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYD Dengue Vaccine Group | Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | 9 Cases |
| Placebo Group | Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | 16 Cases |
Secondary
Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature \>=38°C on at least 2 consecutive days) requiring hospitalization.
Time frame: From consent to participate in the Surveillance Expansion Period to end of the study (up to 72 months)
Population: Analysis was performed in the Safety Analysis Set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYD Dengue Vaccine Group | Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | 5 Cases |
| Placebo Group | Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | 2 Cases |
Secondary
Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature \>=38°C on at least 2 consecutive days) requiring hospitalization.
Time frame: Day 0 up to the end of study (up to 72 months)
Population: Number of hospitalized dengue hemorrhagic fever cases were assessed in the Safety Analysis Set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYD Dengue Vaccine Group | Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | 46 Cases |
| Placebo Group | Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | 71 Cases |
Secondary
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo
Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 reactions (9-11 years): Pain: incapacitating, unable to perform usual activities; Erythema and Swelling, \>= 50 mm. Grade 3 Solicited injection site reactions (12-16 years): Pain: significant, prevents daily activity; Erythema and Swelling, \>100 mm.
Time frame: Within 7 days after each and any injection
Population: Solicited injection site reactions were assessed in a subset of the Safety Analysis Set, which included all participants who received at least one dose of study vaccine and who were evaluated for reactogenicity. Here, 'number analyzed' = participants with available data for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post any injection) | 650 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-any injection) | 83 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-any injection) | 77 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 1) | 430 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Pain (Post-injection 1) | 11 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 1) | 55 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Erythema (Post-injection 1) | 0 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-injection 1) | 47 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Swelling (Post-injection 1) | 0 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 2) | 332 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Pain (Post-injection 2) | 7 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 2) | 25 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Erythema (Post-injection 2) | 1 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-injection 2) | 25 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Swelling (Post-injection 2) | 0 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 3) | 288 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Pain (Post-injection 3) | 11 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 3) | 19 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Erythema (Post-injection 3) | 0 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-injection 3) | 20 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Swelling (Post-injection 3) | 0 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Pain (Post-injection 2) | 0 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post any injection) | 270 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Erythema (Post-injection 3) | 0 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-any injection) | 44 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 2) | 11 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-any injection) | 27 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Pain (Post-injection 3) | 2 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 1) | 173 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Erythema (Post-injection 2) | 0 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Pain (Post-injection 1) | 6 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Swelling (Post-injection 3) | 0 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 1) | 31 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-injection 2) | 6 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Erythema (Post-injection 1) | 1 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 3) | 10 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-injection 1) | 18 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Swelling (Post-injection 2) | 0 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Swelling (Post-injection 1) | 1 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-injection 3) | 8 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 2) | 105 Participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 3) | 104 Participants |
Secondary
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo
Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Asthenia. Grade 3 reactions: Fever: \>= 39°C; Headache, Malaise, Myalgia, and Asthenia: significant, prevents daily activity.
Time frame: Within 14 days after each and any injection
Population: Solicited systemic reactions were assessed in a subset of the Safety Analysis Set, which included all participants who received at least one dose of study vaccine and who were evaluated for reactogenicity. Here, 'number analyzed' = participants with available data for specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 1) | 324 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 2) | 27 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 1) | 86 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 2) | 270 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 1) | 32 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 2) | 17 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post any injection) | 576 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 2) | 273 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 1) | 386 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 2) | 21 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 1) | 21 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 2) | 231 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 1) | 29 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 2) | 24 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Malaise (Post any injection) | 536 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 3) | 89 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 1) | 326 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 3) | 13 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 1) | 528 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 3) | 378 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 1) | 36 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 3) | 33 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post any injection) | 496 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 3) | 246 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 2) | 72 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 3) | 18 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 1) | 67 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 3) | 255 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 2) | 10 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 3) | 19 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Headache (Post any injection) | 727 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 3) | 208 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 2) | 386 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 3) | 17 Participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Fever (Post any injection) | 220 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 3) | 8 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Fever (Post any injection) | 123 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Headache (Post any injection) | 379 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Malaise (Post any injection) | 261 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post any injection) | 267 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post any injection) | 251 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 1) | 42 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 1) | 7 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 1) | 273 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 1) | 27 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 1) | 170 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 1) | 15 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 1) | 180 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 1) | 10 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 1) | 148 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 1) | 17 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 2) | 42 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 2) | 7 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 2) | 182 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 2) | 15 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 2) | 106 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 2) | 8 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 2) | 101 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 2) | 5 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 2) | 105 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 2) | 7 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 3) | 52 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 3) | 5 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 3) | 158 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 3) | 12 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 3) | 96 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 3) | 7 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 3) | 116 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 3) | 5 Participants |
| Placebo Group | Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 3) | 110 Participants |
Secondary
Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase Following Injection With Either CYD Dengue Vaccine or a Placebo
Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time frame: Day 0 up to 13 months post-injection 3
Population: Number of symptomatic VCD cases were assessed in the Full Analysis Set for Efficacy, which included all participants who received at least 1 injection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase Following Injection With Either CYD Dengue Vaccine or a Placebo | 277 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase Following Injection With Either CYD Dengue Vaccine or a Placebo | 385 Cases |
Comparison: The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy (expressed in %) calculated using the exact method conditional on the total number of cases in both groups.95% CI: [58.7, 69.8]
Secondary
Number of Symptomatic VCD Cases Due to Any Serotype Occurring 28 Days Post-dose 1 Following Injection With Either CYD Dengue Vaccine or a Placebo
Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time frame: 28 days post-injection 1 and up to 13 months post-injection 3
Population: Number of symptomatic VCD cases were assessed in the Full Analysis Set for Efficacy, which included participants who received at least 1 dose of study vaccine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Due to Any Serotype Occurring 28 Days Post-dose 1 Following Injection With Either CYD Dengue Vaccine or a Placebo | 273 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Due to Any Serotype Occurring 28 Days Post-dose 1 Following Injection With Either CYD Dengue Vaccine or a Placebo | 380 Cases |
Comparison: The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy (expressed in %) calculated using the exact method conditional on the total number of cases in both groups.95% CI: [58.7, 69.9]
Secondary
Number of Symptomatic VCD Cases Due to Any Serotype Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo
Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.
Time frame: 28 days post-injection 2 and up to 13 months post-injection 3
Population: Number of symptomatic VCD cases were assessed in the Other Efficacy Analysis Set, which included participants who received at least 2 doses of study vaccine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Due to Any Serotype Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo | 236 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Due to Any Serotype Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo | 306 Cases |
Comparison: The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy (expressed in %) calculated using the exact method conditional on the total number of cases in both groups.95% CI: [54.7, 68]
Secondary
Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
The 1997 WHO criteria are: a) Fever: acute onset, high (\>= 38°C) and continuous, for 2 to 7 days and (b) any of the following: thrombocytopenia (platelet \<=100 x 109/L) and plasma leakage as shown by hematocrit increased by 20% or more or pleural effusion and/or ascites and/or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participant, usually in the form of skin and/or other hemorrhages; Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness; and Grade IV: Profound shock with undetectable blood pressure and pulse.
Time frame: From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)
Population: Number of WHO dengue hemorrhagic fever cases were assessed in the Full Analysis Set for Surveillance Expansion Period, which included all participants who received at least 1 injection and accepted to be included in the Surveillance Expansion Period.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade I | 0 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade III | 0 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade II | 2 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade IV | 0 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Any Grade | 2 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade IV | 0 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Any Grade | 0 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade I | 0 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade II | 0 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade III | 0 Cases |
Secondary
Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Dengue hemorrhagic fever (DHF) cases were defined as number of participants with at least one symptomatic VCD episode meeting the 1997 WHO criteria. (a) Fever: acute onset, high (\>= 38°C) and continuous, lasting 2 to 7 days and (b) any of the pre-listed hemorrhagic manifestations and laboratory findings of thrombocytopenia (platelet \<=100 x 109/L) and plasma leakage as shown by hemoconcentration (hematocrit increased by 20% or more) or pleural effusion (seen on CXR) and/or ascites and/ or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish a clinical diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhage.
Time frame: Day 0 to the end of study (up to 72 months)
Population: Number of WHO dengue hemorrhagic fever cases were assessed in the Safety Analysis Set, which included all participants who received at least one dose of study vaccine. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade I | 0 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade III | 0 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade II | 7 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade IV | 0 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Any Grade | 7 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade IV | 0 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Any Grade | 15 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade I | 2 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade II | 13 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade III | 0 Cases |
Secondary
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo
Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (parental strains) were measured by the plaque reduction neutralization test in a pre-defined subset of participants.
Time frame: Pre-injection 1, 28 days post Injections 2 and 3, 13 months (Visit [V] 07) and 60 months (Visit [V] 12) post-injection 3
Population: Antibody titers against each dengue virus serotype strain were assessed in Full Analysis Set for Immunogenicity(FASI),which included a subset of participants who received at least one dose of vaccine and had a blood sample drawn and result available after the dose.Here, 'number analyzed'=participants with available data for each specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1: Pre-Inj.1 | 72.8 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1: Post-Inj. 2 | 92.7 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1: Post-Inj. 3 | 94.9 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; 1 year Post-Inj. 3 (V 07) | 85.6 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; 5 year Post-Inj. 3 (V 12) | 90.0 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Pre-Inj. 1 | 76.1 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Post-Inj. 2 | 97.5 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Post-Inj. 3 | 98.5 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; 1 year Post-Inj. 3 (V 07) | 94.1 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; 5 year Post-Inj. 3 (V 12) | 93.5 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Pre-Inj. 1 | 76.5 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Post-Inj. 2 | 98.5 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Post-Inj. 3 | 98.4 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; 1 year Post-Inj. 3 (V 07) | 92.7 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; 5 year Post-Inj. 3 (V 12) | 95.4 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Pre-Inj. 1 | 68.2 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Post-Inj. 2 | 96.9 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Post-Inj. 3 | 98.1 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; 1 year Post-Inj. 3 (V 07) | 94.9 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; 5 year Post-Inj. 3 (V 12) | 96.3 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Post-Inj. 3 | 68.9 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1: Pre-Inj.1 | 70.5 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Pre-Inj. 1 | 73.6 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1: Post-Inj. 2 | 71.8 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Pre-Inj. 1 | 65.0 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1: Post-Inj. 3 | 74.2 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Post-Inj. 2 | 75.7 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; 1 year Post-Inj. 3 (V 07) | 73.6 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; 5 year Post-Inj. 3 (V 12) | 78.9 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; 5 year Post-Inj. 3 (V 12) | 81.1 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Post-Inj. 3 | 78.0 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Pre-Inj. 1 | 73.8 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Post-Inj. 2 | 67.0 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Post-Inj. 2 | 75.1 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; 1 year Post-Inj. 3 (V 07) | 76.2 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Post-Inj. 3 | 77.2 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; 1 year Post-Inj. 3 (V 07) | 69.0 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; 1 year Post-Inj. 3 (V 07) | 78.9 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; 5 year Post-Inj. 3 (V 12) | 82.7 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; 5 year Post-Inj. 3 (V 12) | 83.1 Percentage of participants |