Dengue, Dengue Fever, Dengue Hemorrhagic Fever
Conditions
Keywords
Dengue, Dengue fever, Dengue Hemorrhagic Fever, CYD dengue vaccine, Flavivirus
Brief summary
The aim of the trial was to assess the efficacy of the CYD dengue vaccine in preventing symptomatic, virologically-confirmed dengue (VCD) cases. Primary Objective: To assess the efficacy of CYD dengue vaccine after 3 vaccinations at 0, 6, and 12 months in preventing symptomatic VCD cases, regardless of the severity, due to any of the four serotypes in children aged 2 to 14 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 serious adverse events (SAEs), including SAEs of special interest in all participants throughout the trial period. * To describe the occurrence of hospitalized virologically-confirmed dengue (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 to 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.
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 were also evaluated for reactogenicity and immunogenicity. 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 confirmed dengue (hospitalized or not) in order to describe CYD dengue vaccine efficacy and safety in preventing symptomatic dengue. 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 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 1997 WHO Classification Dengue hemorrhagic fever (DHF) cases were defined as per the 1997 WHO criteria of clinical manifestations; 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 hemoconcentation (hematocrit increased by 20 percent \[%\] or more) or pleural effusion (seen on chest X-ray \[CXR\]) and/or ascites and/or hypoaluminemia. 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 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. Independent Data Monitoring Committee (IDMC) severity criteria The severity of VCD cases was assessed by an Independent IDMC using pre-defined standardized criteria. Following manifestations of severity were considered in all suspected VCD cases; 1) Platelet count \<= 100000μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage (effusion on CXR OR clinically apparent ascites or hematocrit \>=20% above baseline recovery level) 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 convulsionsfitting not attributable to simple febrile convulsion as defined in the guidelines for definition and collection of febrile convulsions or focal neurological signs. Poor conscious state or unconsciousness must be supported by Glasgow Coma Scale (GCS) score. 5) Liver impairment (aspartate aminotransferase \[AST\] \>1000IU/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, electrocardiogram (ECG) or cardiac enzymes. The designation of such cases as severe or otherwise will be made on a case by case basis by the IDMC.
Interventions
0.5 mL, Subcutaneous
BIOLOGICALPlacebo: Sodium chloride (NaCl) 0.9%
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
2 Years to 14 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 2 to 14 years on the day of inclusion and resident of the site zone * Participant was 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 attended all scheduled visits and to comply with all trial procedures.
Exclusion criteria
* Participant was pregnant, or lactating, or was 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 might interfere with the 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 (Inj.) With Either CYD Dengue Vaccine or a Placebo | 28 days and up to 13 months post-dose 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 and/or dengue NS protein 1 antigen enzyme-linked immunosorbent assay. 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 Vaccine Group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Pre-injection 1, 28 days post Injections 2 and 3, 13 months (V 07) and 60 months (V 12) post-injection 3 | Percentage of participants with antibody titers \>= 10 (1/Dil) against each serotypes of the dengue virus strains were assessed using PRNT in a pre-defined subset of participants. |
| 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 reverse transcriptase polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay. 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 Vaccine Group. |
| Number of Symptomatic VCD Cases Due to Any Serotype 28 Days 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 reverse transcriptase polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay. 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 Vaccine Group. |
| Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase in Either CYD Dengue Vaccine or Placebo Group | 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 reverse transcriptase polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay. 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 Vaccine Group. |
| Number of Symptomatic VCD Cases Meeting 1997 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 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 hemoconcentation (hematocrit increased by 20% or more) or pleural effusion (seen on CXR) and/or ascites and/or hypoaluminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish a clinical diagnosis of DHF. Dengue hemorrhagic fever 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 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | From consent to participate int the Surveillance Expansion Period to 60 months post-injection 3 (up to Month 72) | 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 hypoaluminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish diagnosis of DHF. Dengue hemorrhagic fever 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. |
| Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain 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 (Visit 07) and 60 months (Visit 12) post-injection 3 | Geometric mean titers against each of the 4 serotypes of dengue virus strains were assessed using the plaque reduction neutralization test (PRNT) in a pre-defined subset of participants. |
| Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | From consent to participate in the Surveillance Expansion Period to 60 months post-injection 3 (up to Month 72) | 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 \<=100000μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure \<= 20mmHg 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. |
| Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Within 7 days after injection | Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 reactions (2-11 years): Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, \>= 50 mm. Grade 3 Solicited injection site reactions (12-14 years): Pain, Significant, prevents daily activity; Erythema and Swelling, \>100 mm. |
| Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Within 14 days after 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 Hospitalized 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) | Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS1 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 60 months post-injection 3 (up to Month 72) | Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS1 ELISA in participants with acute febrile illness (temperature \>= 38°C on at least 2 consecutive days) requiring hospitalization. |
| Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Inj. 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 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. |
Countries
Indonesia, Malaysia, Philippines, Thailand, Vietnam
Participant flow
Recruitment details
Study participants were enrolled from 03 June 2011 to 01 December 2011 at 9 sites in Indonesia, 5 in Malaysia, 3 in Thailand, 5 in Philippines, and 2 in Vietnam.
Pre-assignment details
A total of 10275 participants were enrolled; all but one met all of the inclusion criteria and none of the exclusion criteria. Three participants were not vaccinated and were excluded from the Full Analysis Set for Efficacy and the Safety Analysis Set.
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). | 6,851 |
| Placebo Group Participants received 3 doses of placebo 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). | 3,424 |
| Total | 10,275 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Surveillance Expansion Period | Lost to Follow-up | 10 | 8 |
| Surveillance Expansion Period | Protocol Violation | 9 | 1 |
| Surveillance Expansion Period | Serious adverse event | 3 | 4 |
| Surveillance Expansion Period | Withdrawal by Subject | 180 | 105 |
| Vaccination Phase (Up to 25 Months) | Lost to Follow-up | 5 | 1 |
| Vaccination Phase (Up to 25 Months) | Protocol Violation | 5 | 2 |
| Vaccination Phase (Up to 25 Months) | Serious adverse event | 4 | 1 |
| Vaccination Phase (Up to 25 Months) | Withdrawal by Subject | 40 | 23 |
Baseline characteristics
| Characteristic | CYD Dengue Vaccine Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 6851 Participants | 3424 Participants | 10275 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 | 8.8 Years STANDARD_DEVIATION 3.45 | 8.8 Years STANDARD_DEVIATION 3.42 | 8.8 Years STANDARD_DEVIATION 3.44 |
| Region of Enrollment Indonesia | 1246 Participants | 624 Participants | 1870 Participants |
| Region of Enrollment Malaysia | 937 Participants | 464 Participants | 1401 Participants |
| Region of Enrollment Philippines | 2335 Participants | 1166 Participants | 3501 Participants |
| Region of Enrollment Thailand | 778 Participants | 392 Participants | 1170 Participants |
| Region of Enrollment Vietnam | 1555 Participants | 778 Participants | 2333 Participants |
| Sex: Female, Male Female | 3524 Participants | 1767 Participants | 5291 Participants |
| Sex: Female, Male Male | 3327 Participants | 1657 Participants | 4984 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 10 / 6,848 | 4 / 3,424 |
| other Total, other adverse events | 942 / 1,334 | 453 / 663 |
| serious Total, serious adverse events | 947 / 6,848 | 552 / 3,424 |
Outcome results
Primary
Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection (Inj.) 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 and/or dengue NS protein 1 antigen enzyme-linked immunosorbent assay. 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 Vaccine Group.
Time frame: 28 days and up to 13 months post-dose 3
Population: Number of symptomatic VCD cases were assessed in the Per-Protocol Analysis Set for Efficacy
| 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 (Inj.) With Either CYD Dengue Vaccine or a Placebo | 117 Cases |
| Placebo Group | Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection (Inj.) With Either CYD Dengue Vaccine or a Placebo | 133 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: [43.8, 66.4]
Secondary
Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo
Geometric mean titers against each of the 4 serotypes of dengue virus strains were assessed using the plaque reduction neutralization test (PRNT) in a pre-defined subset of participants.
Time frame: Pre-injection 1, 28 days post Injections 2 and 3, 13 months (Visit 07) and 60 months (Visit 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 (GEOMETRIC_MEAN) |
|---|---|---|---|
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Pre-Inj. 1 | 38.3 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Post Inj. 3 | 166 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Year 1 Post Inj. 3 (V 07) | 105 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Year 5 Post Inj. 3 (V 12) | 81.2 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Pre-Inj. 1 | 55.3 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Post Inj. 2 | 360 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Post Inj. 3 | 355 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Year 5 Post-Inj. 3 (V 12) | 144 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Pre-Inj. 1 | 40.1 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Post Inj. 2 | 203 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Post Inj. 3 | 207 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Year 1 Post Inj. 3 (V 07) | 186 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Year 5 Post Inj. 3 (V 12) | 120 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Pre Inj. 1 | 25.3 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Post Inj. 3 | 151 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Year 1 Post Inj. 3 (V 07) | 85.5 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Year 5 Post Inj. 3 (V 12) | 65.7 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Post Inj. 2 | 153 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Year 1 Post-Inj. 3 (V 07) | 194 Titers (1/dilution) |
| CYD Dengue Vaccine Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Post Inj. 2 | 151 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Post Inj. 2 | 40.8 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Post Inj. 2 | 46.1 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Pre-Inj. 1 | 42.1 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Post Inj. 3 | 46.6 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Post Inj. 3 | 42.5 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Year 1 Post Inj. 3 (V 07) | 57.2 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Post Inj. 3 | 26.0 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 1; Year 5 Post Inj. 3 (V 12) | 77.6 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Year 1 Post Inj. 3 (V 07) | 62.1 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Pre-Inj. 1 | 62.1 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Year 5 Post Inj. 3 (V 12) | 40.1 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Post Inj. 2 | 69.5 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Year 5 Post Inj. 3 (V 12) | 76.2 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Post Inj. 3 | 68.5 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Year 1 Post-Inj. 3 (V 07) | 78.1 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Year 1 Post Inj. 3 (V 07) | 26.0 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 2; Year 5 Post-Inj. 3 (V 12) | 102 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Pre Inj. 1 | 26.2 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 3; Pre-Inj. 1 | 40.7 Titers (1/dilution) |
| Placebo Group | Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo | Dengue virus Serotype 4; Post Inj. 2 | 24.4 Titers (1/dilution) |
Secondary
Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Inj. 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 \<=100000μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure \<= 20mmHg 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 60 months post-injection 3 (up to Month 72)
Population: Number of clinically severe VCD cases were assessed in the Full Analysis Set for SEP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYD Dengue Vaccine Group | Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | 21 Cases |
| Placebo Group | Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | 12 Cases |
Secondary
Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Inj. 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: 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, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CYD Dengue Vaccine Group | Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | 61 Cases |
| Placebo Group | Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | 41 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 NS1 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 60 months post-injection 3 (up to Month 72)
Population: Number of hospitalized dengue hemorrhagic fever cases were assessed 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 | 74 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 | 48 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 NS1 ELISA in participants with acute febrile illness (temperature \>=38°C on at least 2 consecutive days) requiring hospitalization.
Time frame: Day 0 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, 'number analyzed' = participants with available data for specified category.
| 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 | 210 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 | 154 Cases |
Secondary
Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo
Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 reactions (2-11 years): Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, \>= 50 mm. Grade 3 Solicited injection site reactions (12-14 years): Pain, Significant, prevents daily activity; Erythema and Swelling, \>100 mm.
Time frame: Within 7 days after 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post any injection) | 614 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-any injection) | 107 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post any injection) | 68 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 1) | 406 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Pain (Post-injection 1) | 1 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 1) | 63 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. 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 Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-injection 1) | 40 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. 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 Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 2) | 303 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Pain (Post-injection 2) | 0 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 2) | 43 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Erythema (Post-injection 2) | 0 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. 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 Inj. 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 Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 3) | 283 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Pain (Post-injection 3) | 0 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 3) | 36 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. 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 Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-injection 3) | 19 participants |
| CYD Dengue Vaccine Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. 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 Inj. 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 Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post any injection) | 275 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Erythema (Post-injection 3) | 1 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-any injection) | 52 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 2) | 20 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post any injection) | 33 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Pain (Post-injection 3) | 0 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 1) | 196 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. 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 Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Pain (Post-injection 1) | 0 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. 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 Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 1) | 35 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-injection 2) | 7 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Erythema (Post-injection 1) | 0 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Erythema (Post-injection 3) | 16 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-injection 1) | 19 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. 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 Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Injection-site Swelling (Post-injection 1) | 0 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Swelling (Post-injection 3) | 10 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 2) | 135 participants |
| Placebo Group | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Injection-site Pain (Post-injection 3) | 118 participants |
Secondary
Number of Participants With Systemic Reactions Following Any and Each Inj. 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 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Fever (Post any injection) | 248 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Headache (Post any injection) | 562 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Malaise (Post any injection) | 476 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post any injection) | 414 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post any injection) | 378 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 1) | 103 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 1) | 18 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 1) | 387 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 1) | 7 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 1) | 312 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 1) | 7 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 1) | 255 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 1) | 2 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 1) | 229 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 1) | 5 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 2) | 90 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 2) | 19 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 2) | 247 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 2) | 12 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 2) | 192 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 2) | 6 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 2) | 174 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 2) | 3 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 2) | 158 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 2) | 5 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 3) | 76 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 3) | 16 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 3) | 219 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 3) | 183 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 3) | 7 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 3) | 156 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 3) | 3 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 3) | 142 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 3) | 4 participants |
| CYD Dengue Vaccine Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 3) | 6 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 3) | 2 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Fever (Post any injection) | 118 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 2) | 3 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Headache (Post any injection) | 259 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 3) | 113 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Malaise (Post any injection) | 239 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 2) | 100 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post any injection) | 197 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 3) | 1 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post any injection) | 167 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 2) | 4 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 3) | 0 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 1) | 7 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 2) | 92 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 1) | 168 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 3) | 104 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Headache (Post-injection 1) | 6 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 2) | 0 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Malaise (Post-injection 1) | 148 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 1) | 45 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 1) | 4 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 2) | 74 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 1) | 124 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Malaise (Post-injection 3) | 1 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Myalgia (Post-injection 1) | 2 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 2) | 6 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 1) | 97 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Asthenia (Post-injection 3) | 73 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Asthenia (Post-injection 1) | 5 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 3) | 39 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Fever (Post-injection 2) | 44 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Myalgia (Post-injection 3) | 76 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 2) | 9 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Grade 3 Fever (Post-injection 3) | 2 participants |
| Placebo Group | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Headache (Post-injection 2) | 118 participants |
Secondary
Number of Symptomatic VCD Cases Due to Any Serotype 28 Days 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 reverse transcriptase polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay. 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 Vaccine 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 28 Days Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo | 205 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Due to Any Serotype 28 Days Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo | 238 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: [49, 65.2]
Secondary
Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase in Either CYD Dengue Vaccine or Placebo Group
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 and/or dengue NS1 enzyme-linked immunosorbent assay. 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 Vaccine 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 in Either CYD Dengue Vaccine or Placebo Group | 286 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase in Either CYD Dengue Vaccine or Placebo Group | 309 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: [46.8, 61.7]
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 reverse transcriptase polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay. 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 Vaccine 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 | 276 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 | 302 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: [47.3, 62.3]
Secondary
Number of Symptomatic VCD Cases Meeting 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. 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 hypoaluminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish diagnosis of DHF. Dengue hemorrhagic fever 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 int the Surveillance Expansion Period to 60 months post-injection 3 (up to Month 72)
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 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade I | 5 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade III | 3 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade II | 11 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. 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 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Any Grade | 19 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. 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 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Any Grade | 12 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade I | 3 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade II | 8 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo | Due to Any of the 4 Serotypes: Grade III | 1 Cases |
Secondary
Number of Symptomatic VCD Cases Meeting 1997 WHO Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo
Dengue hemorrhagic fever 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 hemoconcentation (hematocrit increased by 20% or more) or pleural effusion (seen on CXR) and/or ascites and/or hypoaluminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish a clinical diagnosis of DHF. Dengue hemorrhagic fever 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, 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting 1997 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 | 55 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting 1997 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 | 14 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting 1997 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 | 37 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting 1997 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 | 4 Cases |
| CYD Dengue Vaccine Group | Number of Symptomatic VCD Cases Meeting 1997 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 1997 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 1997 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 | 41 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting 1997 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 | 3 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting 1997 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 | 9 Cases |
| Placebo Group | Number of Symptomatic VCD Cases Meeting 1997 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 | 29 Cases |
Secondary
Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo
Percentage of participants with antibody titers \>= 10 (1/Dil) against each serotypes of the dengue virus strains were assessed using PRNT 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 (NUMBER) |
|---|---|---|---|
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; Pre-Inj. 1 | 52.0 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; Post Inj. 2 | 88.9 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; Post-Inj. 3 | 94.0 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; Year 1 Post-Inj. 3 (V 07) | 79.8 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; Year 5 Post-Inj 3 (V 12) | 76.2 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Pre-Inj. 1 | 58.0 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Post-Inj. 2 | 97.3 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Post-Inj. 3 | 98.7 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Year 1 Post-Inj. 3 (V 07) | 92.0 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Year 5 Post-inj 3 (V 12) | 86 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Pre-Inj. 1 | 56.8 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Post-Inj. 2 | 95.7 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Post-Inj. 3 | 97.0 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Year 1 Post-Inj. 3 (V 07) | 93.6 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Year5 Post-Inj. 3 (V 12) | 87.4 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Pre-Inj. 1 | 51.6 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Post-Inj. 2 | 95.1 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Post-Inj. 3 | 97.0 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Year 1 Post-Inj 3 (V 07) | 89.4 Percentage of participants |
| CYD Dengue Vaccine Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Year 5 Post-Inj 3 (V 12) | 83.8 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Post-Inj. 3 | 53.9 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; Pre-Inj. 1 | 51.3 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Pre-Inj. 1 | 59.4 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; Post Inj. 2 | 54.4 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Pre-Inj. 1 | 50.7 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; Post-Inj. 3 | 55.4 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Post-Inj. 2 | 60.2 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; Year 1 Post-Inj. 3 (V 07) | 55.7 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Year 5 Post-Inj 3 (V 12) | 65.0 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 1; Year 5 Post-Inj 3 (V 12) | 70.0 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Post-Inj. 3 | 61.0 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Pre-Inj. 1 | 59.3 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Post-Inj. 2 | 51.8 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Post-Inj. 2 | 62.4 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Year 1 Post-Inj. 3 (V 07) | 62.6 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Post-Inj. 3 | 61.8 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 4; Year 1 Post-Inj 3 (V 07) | 50.6 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Year 1 Post-Inj. 3 (V 07) | 65.8 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 3; Year5 Post-Inj. 3 (V 12) | 75.6 Percentage of participants |
| Placebo Group | Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo | Dengue virus Serotype 2; Year 5 Post-inj 3 (V 12) | 75.2 Percentage of participants |