Study of a Novel Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 14 Years in Asia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dengue Vaccine Group Participants were to receive CYD dengue vaccine at 0, 6, and 12 months. |
Biological: Live, attenuated, dengue serotype 1, 2, 3, 4 virus
0.5 mL, Subcutaneous
Other Names:
|
| Placebo Comparator: Control Group Participants were to receive a placebo vaccine at 0, 6, and 12 months. |
Biological: Placebo: Sodium chloride (NaCl) 0.9%
0.5 mL, Subcutaneous
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Denpasar | Bali | Indonesia | 80114 | |
| 2 | Bandung | West Java | Indonesia | 40161 | |
| 3 | Jakarta | Indonesia | 10430 | ||
| 4 | Kuala Lumpur | Malaysia | 50586 | ||
| 5 | Pulau Pinang | Malaysia | 10450 | ||
| 6 | Cebu City | Philippines | 6000 | ||
| 7 | San Pablo City | Philippines | 4000 | ||
| 8 | Nai Muang | Kamphaeng Phet Province | Thailand | 6200 | |
| 9 | Ban Pong | Ratchaburi Province | Thailand | 70110 | |
| 10 | Photharam | Ratchaburi Province | Thailand | 70120 | |
| 11 | Long Xuyên | An Giang Province | Vietnam | ||
| 12 | Mỹ Tho | Tien Giang Province | Vietnam |
Sponsors and Collaborators
- Sanofi Pasteur, a Sanofi Company
Investigators
- Study Director: Medical Director, Sanofi Pasteur SA
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CYD14
- UTN: U1111-1116-4957
- 2014-001708-24
Study Results
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 Detail | 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. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | 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). | 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). |
| Period Title: Vaccination Phase (Up to 25 Months) | ||
| STARTED | 6851 | 3424 |
| COMPLETED | 6797 | 3397 |
| NOT COMPLETED | 54 | 27 |
| Period Title: Vaccination Phase (Up to 25 Months) | ||
| STARTED | 6797 | 3397 |
| COMPLETED | 6595 | 3279 |
| NOT COMPLETED | 202 | 118 |
Baseline Characteristics
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group | Total |
|---|---|---|---|
| Arm/Group Description | 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). | 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). | Total of all reporting groups |
| Overall Participants | 6851 | 3424 | 10275 |
| Age (Count of Participants) | |||
| <=18 years |
6851
100%
|
3424
100%
|
10275
100%
|
| Between 18 and 65 years |
0
0%
|
0
0%
|
0
0%
|
| >=65 years |
0
0%
|
0
0%
|
0
0%
|
| Age (Years) [Mean (Standard Deviation) ] | |||
| Age Continuous |
8.8
(3.45)
|
8.8
(3.42)
|
8.8
(3.44)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
3524
51.4%
|
1767
51.6%
|
5291
51.5%
|
| Male |
3327
48.6%
|
1657
48.4%
|
4984
48.5%
|
| Region of Enrollment (Count of Participants) | |||
| Philippines |
2335
34.1%
|
1166
34.1%
|
3501
34.1%
|
| Malaysia |
937
13.7%
|
464
13.6%
|
1401
13.6%
|
| Indonesia |
1246
18.2%
|
624
18.2%
|
1870
18.2%
|
| Thailand |
778
11.4%
|
392
11.4%
|
1170
11.4%
|
| Vietnam |
1555
22.7%
|
778
22.7%
|
2333
22.7%
|
Outcome Measures
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of symptomatic VCD cases were assessed in the Per-Protocol Analysis Set for Efficacy |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. | Participants were to receive 3 doses of placebo vaccine, one each at 0, 6, and 12 months. |
| Measure Participants | 6709 | 3350 |
| Number [Cases] |
117
|
133
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine Group, Placebo Group |
|---|---|---|
| Comments | 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%. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine efficacy |
| Estimated Value | 56.5 | |
| Confidence Interval |
(2-Sided) 95% 43.8 to 66.4 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Subset of participants who received at least one dose of CYD Dengue vaccine. | Subset of participants who received at least one dose of the placebo vaccine. |
| Measure Participants | 1323 | 660 |
| Dengue virus Serotype 1; Pre-Inj. 1 |
38.3
|
42.1
|
| Dengue virus Serotype 1; Post Inj. 2 |
153
|
46.1
|
| Dengue virus Serotype 1; Post Inj. 3 |
166
|
46.6
|
| Dengue virus Serotype 1; Year 1 Post Inj. 3 (V 07) |
105
|
57.2
|
| Dengue virus Serotype 1; Year 5 Post Inj. 3 (V 12) |
81.2
|
77.6
|
| Dengue virus Serotype 2; Pre-Inj. 1 |
55.3
|
62.1
|
| Dengue virus Serotype 2; Post Inj. 2 |
360
|
69.5
|
| Dengue virus Serotype 2; Post Inj. 3 |
355
|
68.5
|
| Dengue virus Serotype 2; Year 1 Post-Inj. 3 (V 07) |
194
|
78.1
|
| Dengue virus Serotype 2; Year 5 Post-Inj. 3 (V 12) |
144
|
102
|
| Dengue virus Serotype 3; Pre-Inj. 1 |
40.1
|
40.7
|
| Dengue virus Serotype 3; Post Inj. 2 |
203
|
40.8
|
| Dengue virus Serotype 3; Post Inj. 3 |
207
|
42.5
|
| Dengue virus Serotype 3; Year 1 Post Inj. 3 (V 07) |
186
|
62.1
|
| Dengue virus Serotype 3; Year 5 Post Inj. 3 (V 12) |
120
|
76.2
|
| Dengue virus Serotype 4; Pre Inj. 1 |
25.3
|
26.2
|
| Dengue virus Serotype 4; Post Inj. 2 |
151
|
24.4
|
| Dengue virus Serotype 4; Post Inj. 3 |
151
|
26.0
|
| Dengue virus Serotype 4; Year 1 Post Inj. 3 (V 07) |
85.5
|
26.0
|
| Dengue virus Serotype 4; Year 5 Post Inj. 3 (V 12) |
65.7
|
40.1
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Subset of participants who received at least one dose of CYD Dengue vaccine | Subset of participants who received at least one dose of placebo vaccine |
| Measure Participants | 1323 | 660 |
| Dengue virus Serotype 1; Pre-Inj. 1 |
52.0
0.8%
|
51.3
1.5%
|
| Dengue virus Serotype 1; Post Inj. 2 |
88.9
1.3%
|
54.4
1.6%
|
| Dengue virus Serotype 1; Post-Inj. 3 |
94.0
1.4%
|
55.4
1.6%
|
| Dengue virus Serotype 1; Year 1 Post-Inj. 3 (V 07) |
79.8
1.2%
|
55.7
1.6%
|
| Dengue virus Serotype 1; Year 5 Post-Inj 3 (V 12) |
76.2
1.1%
|
70.0
2%
|
| Dengue virus Serotype 2; Pre-Inj. 1 |
58.0
0.8%
|
59.3
1.7%
|
| Dengue virus Serotype 2; Post-Inj. 2 |
97.3
1.4%
|
62.4
1.8%
|
| Dengue virus Serotype 2; Post-Inj. 3 |
98.7
1.4%
|
61.8
1.8%
|
| Dengue virus Serotype 2; Year 1 Post-Inj. 3 (V 07) |
92.0
1.3%
|
65.8
1.9%
|
| Dengue virus Serotype 2; Year 5 Post-inj 3 (V 12) |
86
1.3%
|
75.2
2.2%
|
| Dengue virus Serotype 3; Pre-Inj. 1 |
56.8
0.8%
|
59.4
1.7%
|
| Dengue virus Serotype 3; Post-Inj. 2 |
95.7
1.4%
|
60.2
1.8%
|
| Dengue virus Serotype 3; Post-Inj. 3 |
97.0
1.4%
|
61.0
1.8%
|
| Dengue virus Serotype 3; Year 1 Post-Inj. 3 (V 07) |
93.6
1.4%
|
62.6
1.8%
|
| Dengue virus Serotype 3; Year5 Post-Inj. 3 (V 12) |
87.4
1.3%
|
75.6
2.2%
|
| Dengue virus Serotype 4; Pre-Inj. 1 |
51.6
0.8%
|
50.7
1.5%
|
| Dengue virus Serotype 4; Post-Inj. 2 |
95.1
1.4%
|
51.8
1.5%
|
| Dengue virus Serotype 4; Post-Inj. 3 |
97.0
1.4%
|
53.9
1.6%
|
| Dengue virus Serotype 4; Year 1 Post-Inj 3 (V 07) |
89.4
1.3%
|
50.6
1.5%
|
| Dengue virus Serotype 4; Year 5 Post-Inj 3 (V 12) |
83.8
1.2%
|
65.0
1.9%
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. | Participants were to receive 3 doses of placebo vaccine, one each at 0, 6, and 12 months. |
| Measure Participants | 6848 | 3424 |
| Number [Cases] |
276
|
302
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine Group, Placebo Group |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 55.4 | |
| Confidence Interval |
(2-Sided) 95% 47.3 to 62.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Symptomatic VCD Cases Due to Any Serotype 28 Days Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. | Participants were to receive 3 doses of placebo vaccine, one each at 0, 6, and 12 months. |
| Measure Participants | 6793 | 3397 |
| Number [Cases] |
205
|
238
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine Group, Placebo Group |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 57.9 | |
| Confidence Interval |
(2-Sided) 95% 49.0 to 65.2 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase in Either CYD Dengue Vaccine or Placebo Group |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. | Participants were to receive 3 doses of placebo vaccine, one each at 0, 6, and 12 months. |
| Measure Participants | 6848 | 3424 |
| Number [Cases] |
286
|
309
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CYD Dengue Vaccine Group, Placebo Group |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | |
| Comments | ||
| Method | ||
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 54.8 | |
| Confidence Interval |
(2-Sided) 95% 46.8 to 61.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | 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 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. | Participants were to receive 3 doses of placebo vaccine, one each at 0, 6, and 12 months. |
| Measure Participants | 6848 | 3424 |
| Due to Any of the 4 Serotypes: Any Grade |
55
|
41
|
| Due to Any of the 4 Serotypes: Grade I |
14
|
9
|
| Due to Any of the 4 Serotypes: Grade II |
37
|
29
|
| Due to Any of the 4 Serotypes: Grade III |
4
|
3
|
| Due to Any of the 4 Serotypes: Grade IV |
0
|
0
|
| Title | 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 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. | Participant were to receive 3 doses of placebo vaccine, one each at 0, 6, and 12 months. |
| Measure Participants | 6327 | 3138 |
| Due to Any of the 4 Serotypes: Any Grade |
19
|
12
|
| Due to Any of the 4 Serotypes: Grade I |
5
|
3
|
| Due to Any of the 4 Serotypes: Grade II |
11
|
8
|
| Due to Any of the 4 Serotypes: Grade III |
3
|
1
|
| Due to Any of the 4 Serotypes: Grade IV |
0
|
0
|
| Title | Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. | Participant were to receive 3 doses of placebo vaccine, one each at 0, 6, and 12 months. |
| Measure Participants | 6745 | 3369 |
| Number [Cases] |
61
|
41
|
| Title | 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 |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of clinically severe VCD cases were assessed in the Full Analysis Set for SEP. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. | Participant were to receive 3 doses of placebo vaccine, one each at 0, 6, and 12 months. |
| Measure Participants | 6327 | 3138 |
| Number [Cases] |
21
|
12
|
| Title | Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. | Participants were to receive 3 doses of placebo vaccine, one each at 0, 6, and 12 months. |
| Measure Participants | 1334 | 663 |
| Injection-site Pain (Post any injection) |
614
9%
|
275
8%
|
| Injection-site Erythema (Post-any injection) |
107
1.6%
|
52
1.5%
|
| Injection-site Swelling (Post any injection) |
68
1%
|
33
1%
|
| Injection-site Pain (Post-injection 1) |
406
5.9%
|
196
5.7%
|
| Grade 3 Injection-site Pain (Post-injection 1) |
1
0%
|
0
0%
|
| Injection-site Erythema (Post-injection 1) |
63
0.9%
|
35
1%
|
| Grade 3 Injection-site Erythema (Post-injection 1) |
0
0%
|
0
0%
|
| Injection-site Swelling (Post-injection 1) |
40
0.6%
|
19
0.6%
|
| Grade 3 Injection-site Swelling (Post-injection 1) |
0
0%
|
0
0%
|
| Injection-site Pain (Post-injection 2) |
303
4.4%
|
135
3.9%
|
| Grade 3 Injection-site Pain (Post-injection 2) |
0
0%
|
0
0%
|
| Injection-site Erythema (Post-injection 2) |
43
0.6%
|
20
0.6%
|
| Grade 3 Injection-site Erythema (Post-injection 2) |
0
0%
|
0
0%
|
| Injection-site Swelling (Post-injection 2) |
25
0.4%
|
7
0.2%
|
| Grade 3 Injection-site Swelling (Post-injection 2) |
0
0%
|
0
0%
|
| Injection-site Pain (Post-injection 3) |
283
4.1%
|
118
3.4%
|
| Grade 3 Injection-site Pain (Post-injection 3) |
0
0%
|
0
0%
|
| Injection-site Erythema (Post-injection 3) |
36
0.5%
|
16
0.5%
|
| Grade 3 Injection-site Erythema (Post-injection 3) |
0
0%
|
1
0%
|
| Injection-site Swelling (Post-injection 3) |
19
0.3%
|
10
0.3%
|
| Grade 3 Injection-site Swelling (Post-injection 3) |
0
0%
|
0
0%
|
| Title | Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. | Participants were to receive 3 doses of placebo vaccine, one each at 0, 6, and 12 months. |
| Measure Participants | 1334 | 663 |
| Fever (Post any injection) |
248
3.6%
|
118
3.4%
|
| Headache (Post any injection) |
562
8.2%
|
259
7.6%
|
| Malaise (Post any injection) |
476
6.9%
|
239
7%
|
| Myalgia (Post any injection) |
414
6%
|
197
5.8%
|
| Asthenia (Post any injection) |
378
5.5%
|
167
4.9%
|
| Fever (Post-injection 1) |
103
1.5%
|
45
1.3%
|
| Grade 3 Fever (Post-injection 1) |
18
0.3%
|
7
0.2%
|
| Headache (Post-injection 1) |
387
5.6%
|
168
4.9%
|
| Grade 3 Headache (Post-injection 1) |
7
0.1%
|
6
0.2%
|
| Malaise (Post-injection 1) |
312
4.6%
|
148
4.3%
|
| Grade 3 Malaise (Post-injection 1) |
7
0.1%
|
4
0.1%
|
| Myalgia (Post-injection 1) |
255
3.7%
|
124
3.6%
|
| Grade 3 Myalgia (Post-injection 1) |
2
0%
|
2
0.1%
|
| Asthenia (Post-injection 1) |
229
3.3%
|
97
2.8%
|
| Grade 3 Asthenia (Post-injection 1) |
5
0.1%
|
5
0.1%
|
| Fever (Post-injection 2) |
90
1.3%
|
44
1.3%
|
| Grade 3 Fever (Post-injection 2) |
19
0.3%
|
9
0.3%
|
| Headache (Post-injection 2) |
247
3.6%
|
118
3.4%
|
| Grade 3 Headache (Post-injection 2) |
12
0.2%
|
3
0.1%
|
| Malaise (Post-injection 2) |
192
2.8%
|
100
2.9%
|
| Grade 3 Malaise (Post-injection 2) |
6
0.1%
|
4
0.1%
|
| Myalgia (Post-injection 2) |
174
2.5%
|
92
2.7%
|
| Grade 3 Myalgia (Post-injection 2) |
3
0%
|
0
0%
|
| Asthenia (Post-injection 2) |
158
2.3%
|
74
2.2%
|
| Grade 3 Asthenia (Post-injection 2) |
5
0.1%
|
6
0.2%
|
| Fever (Post-injection 3) |
76
1.1%
|
39
1.1%
|
| Grade 3 Fever (Post-injection 3) |
16
0.2%
|
2
0.1%
|
| Headache (Post-injection 3) |
219
3.2%
|
113
3.3%
|
| Grade 3 Headache (Post-injection 3) |
6
0.1%
|
1
0%
|
| Malaise (Post-injection 3) |
183
2.7%
|
104
3%
|
| Grade 3 Malaise (Post-injection 3) |
7
0.1%
|
1
0%
|
| Myalgia (Post-injection 3) |
156
2.3%
|
76
2.2%
|
| Grade 3 Myalgia (Post-injection 3) |
3
0%
|
0
0%
|
| Asthenia (Post-injection 3) |
142
2.1%
|
73
2.1%
|
| Grade 3 Asthenia (Post-injection 3) |
4
0.1%
|
2
0.1%
|
| Title | Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (up to 72 months). | Participants were to receive 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 (up to 72 months). |
| Measure Participants | 6745 | 3369 |
| Number [Cases] |
210
|
154
|
| Title | Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Number of hospitalized dengue hemorrhagic fever cases were assessed in the Safety Analysis Set. |
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group |
|---|---|---|
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (up to 72 months). | Participants were to receive 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 (up to 72 months). |
| Measure Participants | 6848 | 3424 |
| Number [Cases] |
74
|
48
|
Adverse Events
| Time Frame | Adverse event data were collected from Day 0 (post-vaccination) up to 60 months post-injection 3 (up to 72 months). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | All the vaccinated participants were assessed for SAE during the trial. Non-serious adverse events included solicited injection-site (within 7 days after injection) and solicited systemic reactions (within 14 days after injection), as well as unsolicited non-serious adverse events (within 28 days after injection). These events were assessed in a subset of participants from each group, who had received at least 1 dose of study vaccine. | |||
| Arm/Group Title | CYD Dengue Vaccine Group | Placebo Group | ||
| Arm/Group Description | Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months. | Participants were to receive 3 doses of placebo vaccine; one each at 0, 6, and 12 months. | ||
All Cause Mortality |
||||
| CYD Dengue Vaccine Group | Placebo Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 10/6848 (0.1%) | 4/3424 (0.1%) | ||
Serious Adverse Events |
||||
| CYD Dengue Vaccine Group | Placebo Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 947/6848 (13.8%) | 552/3424 (16.1%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Anaemia Of Pregnancy | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Haemorrhagic Anaemia | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Iron Deficiency Anaemia | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Lymphadenitis | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Cardiac disorders | ||||
| Cardiac Failure Congestive | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Cardiogenic Shock | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Rheumatic Heart Disease | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Supraventricular Tachycardia | 1/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Ventricular Tachycardia | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Congenital, familial and genetic disorders | ||||
| Cryptorchism | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Duchenne Muscular Dystrophy | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Familial Periodic Paralysis | 1/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Fibrous Dysplasia Of Bone | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Odontogenic Cyst | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Phimosis | 0/6848 (0%) | 0 | 2/3424 (0.1%) | 2 |
| Ear and labyrinth disorders | ||||
| Middle Ear Effusion | 0/6848 (0%) | 0 | 1/3424 (0%) | 2 |
| Vertigo Positional | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Vestibular Disorder | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Endocrine disorders | ||||
| Goitre | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Eye disorders | ||||
| Chalazion | 3/6848 (0%) | 3 | 0/3424 (0%) | 0 |
| Choroidal Dystrophy | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Corneal Oedema | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal Pain | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Abdominal Pain Lower | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Abdominal Pain Upper | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Anal Fistula | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Caecitis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Colitis | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Dental Caries | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Diarrhoea | 6/6848 (0.1%) | 6 | 6/3424 (0.2%) | 6 |
| Dyspepsia | 8/6848 (0.1%) | 8 | 2/3424 (0.1%) | 2 |
| Enteritis | 5/6848 (0.1%) | 5 | 1/3424 (0%) | 2 |
| Enterocolitis | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Food Poisoning | 9/6848 (0.1%) | 9 | 3/3424 (0.1%) | 3 |
| Gastritis | 31/6848 (0.5%) | 32 | 14/3424 (0.4%) | 16 |
| Gastrointestinal Disorder | 9/6848 (0.1%) | 10 | 5/3424 (0.1%) | 5 |
| Gastrointestinal Haemorrhage | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Gastrointestinal Inflammation | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Gastrooesophageal Reflux Disease | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Haemorrhoids | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Ileus | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Inguinal Hernia | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Mouth Cyst | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Pancreatitis Acute | 1/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Pancreatitis Chronic | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Periodontitis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Peritonitis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Salivary Gland Calculus | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Salivary Gland Mucocoele | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Tooth Development Disorder | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Tooth Impacted | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Toothache | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| General disorders | ||||
| Drowning | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Hernia Obstructive | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Pyrexia | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Hepatobiliary disorders | ||||
| Hepatitis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Immune system disorders | ||||
| Allergy To Arthropod Bite | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Allergy To Arthropod Sting | 4/6848 (0.1%) | 4 | 1/3424 (0%) | 1 |
| Anaphylactic Reaction | 3/6848 (0%) | 3 | 1/3424 (0%) | 1 |
| Anaphylactic Shock | 1/6848 (0%) | 1 | 2/3424 (0.1%) | 2 |
| Drug Hypersensitivity | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Food Allergy | 5/6848 (0.1%) | 5 | 1/3424 (0%) | 1 |
| Hypersensitivity | 2/6848 (0%) | 2 | 2/3424 (0.1%) | 2 |
| Infections and infestations | ||||
| Abscess Limb | 4/6848 (0.1%) | 4 | 0/3424 (0%) | 0 |
| Abscess Neck | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Abscess Of External Auditory Meatus | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Acinetobacter Bacteraemia | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Acute Sinusitis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Acute Tonsillitis | 7/6848 (0.1%) | 7 | 2/3424 (0.1%) | 2 |
| Adenoiditis | 4/6848 (0.1%) | 4 | 1/3424 (0%) | 1 |
| Amoebiasis | 9/6848 (0.1%) | 9 | 4/3424 (0.1%) | 4 |
| Amoebic Dysentery | 3/6848 (0%) | 3 | 2/3424 (0.1%) | 2 |
| Anal Abscess | 0/6848 (0%) | 0 | 2/3424 (0.1%) | 2 |
| Appendiceal Abscess | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Appendicitis | 33/6848 (0.5%) | 33 | 27/3424 (0.8%) | 27 |
| Appendicitis Perforated | 5/6848 (0.1%) | 5 | 4/3424 (0.1%) | 4 |
| Bacterial Diarrhoea | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Bacterial Infection | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Bartholin's Abscess | 2/6848 (0%) | 3 | 0/3424 (0%) | 0 |
| Bronchiolitis | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Bronchitis | 16/6848 (0.2%) | 16 | 6/3424 (0.2%) | 8 |
| Bronchitis Bacterial | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Bronchopneumonia | 8/6848 (0.1%) | 8 | 1/3424 (0%) | 1 |
| Brucellosis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Cellulitis | 7/6848 (0.1%) | 7 | 3/3424 (0.1%) | 3 |
| Chikungunya Virus Infection | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Chronic Tonsillitis | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Conjunctivitis Infective | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Cystitis | 3/6848 (0%) | 3 | 0/3424 (0%) | 0 |
| Dengue Fever | 238/6848 (3.5%) | 241 | 158/3424 (4.6%) | 167 |
| Diarrhoea Infectious | 3/6848 (0%) | 3 | 5/3424 (0.1%) | 5 |
| Disseminated Tuberculosis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Encephalitis Viral | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Endophthalmitis | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Furuncle | 3/6848 (0%) | 3 | 0/3424 (0%) | 0 |
| Gastritis Bacterial | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Gastroenteritis | 53/6848 (0.8%) | 64 | 40/3424 (1.2%) | 43 |
| Gastroenteritis Bacterial | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Gastroenteritis Viral | 3/6848 (0%) | 3 | 1/3424 (0%) | 1 |
| Gastrointestinal Bacterial Infection | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Gastrointestinal Infection | 6/6848 (0.1%) | 6 | 5/3424 (0.1%) | 5 |
| Groin Abscess | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Hiv Infection | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Hand-Foot-And-Mouth Disease | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Hepatitis A | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Hepatitis Viral | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Herpangina | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Herpes Zoster | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Hordeolum | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Infection In An Immunocompromised Host | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Influenza | 9/6848 (0.1%) | 9 | 3/3424 (0.1%) | 4 |
| Leptospirosis | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Lobar Pneumonia | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Lymphadenitis Bacterial | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Malaria | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Measles | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Meningitis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Meningitis Aseptic | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Meningitis Bacterial | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Mumps | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Nasopharyngitis | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Oral Herpes | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Orchitis | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Otitis Externa | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Otitis Media | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Otitis Media Chronic | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Paratyphoid Fever | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Parotitis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Periorbital Cellulitis | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Peritonsillar Abscess | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Pharyngitis | 32/6848 (0.5%) | 35 | 19/3424 (0.6%) | 25 |
| Pharyngitis Bacterial | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Pharyngitis Streptococcal | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Pharyngotonsillitis | 15/6848 (0.2%) | 15 | 4/3424 (0.1%) | 4 |
| Plasmodium Falciparum Infection | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Pneumonia | 33/6848 (0.5%) | 37 | 12/3424 (0.4%) | 12 |
| Pneumonia Bacterial | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Pneumonia Measles | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Pneumonia Primary Atypical | 2/6848 (0%) | 2 | 2/3424 (0.1%) | 2 |
| Pneumonia Viral | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Postoperative Wound Infection | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Pulmonary Tuberculosis | 5/6848 (0.1%) | 5 | 2/3424 (0.1%) | 2 |
| Pyelonephritis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Pyelonephritis Acute | 4/6848 (0.1%) | 4 | 3/3424 (0.1%) | 3 |
| Respiratory Tract Infection | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Scarlet Fever | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Sepsis | 2/6848 (0%) | 2 | 2/3424 (0.1%) | 2 |
| Sinusitis | 4/6848 (0.1%) | 4 | 2/3424 (0.1%) | 2 |
| Staphylococcal Sepsis | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Streptococcal Infection | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Tonsillitis | 12/6848 (0.2%) | 12 | 4/3424 (0.1%) | 4 |
| Tonsillitis Bacterial | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Tooth Abscess | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Tuberculosis | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Tuberculous Pleurisy | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Typhoid Fever | 15/6848 (0.2%) | 18 | 13/3424 (0.4%) | 13 |
| Typhus | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Upper Respiratory Tract Infection | 11/6848 (0.2%) | 11 | 5/3424 (0.1%) | 6 |
| Urethritis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Urinary Tract Infection | 22/6848 (0.3%) | 23 | 14/3424 (0.4%) | 17 |
| Varicella | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Viral Infection | 32/6848 (0.5%) | 35 | 29/3424 (0.8%) | 29 |
| Viral Pharyngitis | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Viral Rash | 0/6848 (0%) | 0 | 3/3424 (0.1%) | 3 |
| Viral Upper Respiratory Tract Infection | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Vulval Abscess | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Wound Infection | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Accident | 4/6848 (0.1%) | 4 | 1/3424 (0%) | 1 |
| Adverse Event Following Immunisation | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Animal Bite | 2/6848 (0%) | 2 | 4/3424 (0.1%) | 4 |
| Arthropod Bite | 3/6848 (0%) | 3 | 0/3424 (0%) | 0 |
| Burns Second Degree | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Chemical Poisoning | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Chest Injury | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Clavicle Fracture | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Concussion | 7/6848 (0.1%) | 7 | 2/3424 (0.1%) | 2 |
| Contusion | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Ear Injury | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Electrical Burn | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Excoriation | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Eye Injury | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Eyeball Rupture | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Facial Bones Fracture | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Fall | 15/6848 (0.2%) | 16 | 6/3424 (0.2%) | 6 |
| Femur Fracture | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Fibula Fracture | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Foot Fracture | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Forearm Fracture | 9/6848 (0.1%) | 9 | 4/3424 (0.1%) | 4 |
| Foreign Body | 5/6848 (0.1%) | 5 | 0/3424 (0%) | 0 |
| Foreign Body In Eye | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Genital Injury | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Gun Shot Wound | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Hand Fracture | 3/6848 (0%) | 3 | 0/3424 (0%) | 0 |
| Head Injury | 5/6848 (0.1%) | 5 | 4/3424 (0.1%) | 4 |
| Humerus Fracture | 9/6848 (0.1%) | 9 | 2/3424 (0.1%) | 2 |
| Impacted Fracture | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Injury | 1/6848 (0%) | 1 | 2/3424 (0.1%) | 2 |
| Intentional Overdose | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Joint Dislocation | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Joint Injury | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Laceration | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Ligament Sprain | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Limb Injury | 1/6848 (0%) | 1 | 3/3424 (0.1%) | 3 |
| Lower Limb Fracture | 1/6848 (0%) | 1 | 2/3424 (0.1%) | 2 |
| Multiple Fractures | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Multiple Injuries | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Muscle Strain | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Near Drowning | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Open Wound | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Overdose | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Poisoning Deliberate | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Postoperative Adhesion | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Postoperative Ileus | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Radius Fracture | 6/6848 (0.1%) | 6 | 5/3424 (0.1%) | 5 |
| Road Traffic Accident | 71/6848 (1%) | 75 | 38/3424 (1.1%) | 39 |
| Scrotal Haematoma | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Snake Bite | 4/6848 (0.1%) | 4 | 0/3424 (0%) | 0 |
| Soft Tissue Injury | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Sports Injury | 5/6848 (0.1%) | 5 | 1/3424 (0%) | 1 |
| Stab Wound | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Tendon Rupture | 3/6848 (0%) | 3 | 0/3424 (0%) | 0 |
| Thermal Burn | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Tibia Fracture | 1/6848 (0%) | 1 | 2/3424 (0.1%) | 2 |
| Toxicity To Various Agents | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Tracheal Injury | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Traumatic Brain Injury | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Traumatic Intracranial Haemorrhage | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Upper Limb Fracture | 3/6848 (0%) | 3 | 2/3424 (0.1%) | 2 |
| Metabolism and nutrition disorders | ||||
| Calcium Deficiency | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Hypocalcaemia | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Hypoglycaemia | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Hypokalaemia | 2/6848 (0%) | 3 | 1/3424 (0%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Bone Cyst | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Exostosis | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Fasciitis | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Fracture Malunion | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Jaw Cyst | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Muscle Spasms | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Myositis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Rheumatic Fever | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Synovial Cyst | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Synovitis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Acute Lymphocytic Leukaemia | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Angiofibroma | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Benign Neoplasm Of Skin | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Benign Soft Tissue Neoplasm | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Bone Giant Cell Tumour Benign | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Bone Sarcoma | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Breast Neoplasm | 3/6848 (0%) | 3 | 0/3424 (0%) | 0 |
| Ear Neoplasm | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Fibroadenoma Of Breast | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Fibrous Histiocytoma | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Haemangioma | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Lip Neoplasm Benign | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Lipoma | 0/6848 (0%) | 0 | 2/3424 (0.1%) | 2 |
| Lymphangioma | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Skin Papilloma | 0/6848 (0%) | 0 | 2/3424 (0.1%) | 2 |
| Soft Tissue Neoplasm | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Teratoma | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Nervous system disorders | ||||
| Acute Disseminated Encephalomyelitis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Autonomic Neuropathy | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Cerebral Venous Thrombosis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Complex Partial Seizures | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Convulsion | 4/6848 (0.1%) | 4 | 2/3424 (0.1%) | 2 |
| Convulsions Local | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Encephalitis | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Epilepsy | 8/6848 (0.1%) | 9 | 4/3424 (0.1%) | 7 |
| Extrapyramidal Disorder | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Febrile Convulsion | 13/6848 (0.2%) | 23 | 7/3424 (0.2%) | 7 |
| Grand Mal Convulsion | 2/6848 (0%) | 3 | 0/3424 (0%) | 0 |
| Guillain-Barre Syndrome | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Intercostal Neuralgia | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Ischaemic Stroke | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Migraine Without Aura | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Partial Seizures | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Presyncope | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Status Epilepticus | 1/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Syncope | 2/6848 (0%) | 3 | 0/3424 (0%) | 0 |
| Tension Headache | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Tonic Convulsion | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Viith Nerve Paralysis | 3/6848 (0%) | 3 | 0/3424 (0%) | 0 |
| Pregnancy, puerperium and perinatal conditions | ||||
| Abortion Complete | 3/6848 (0%) | 4 | 0/3424 (0%) | 0 |
| Abortion Incomplete | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Abortion Spontaneous | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Abortion Spontaneous Incomplete | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Abortion Threatened | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Breech Presentation | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Cephalo-Pelvic Disproportion | 3/6848 (0%) | 3 | 1/3424 (0%) | 1 |
| Eclampsia | 3/6848 (0%) | 3 | 1/3424 (0%) | 1 |
| Ectopic Pregnancy | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| False Labour | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Foetal Distress Syndrome | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Oligohydramnios | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Postpartum Haemorrhage | 0/6848 (0%) | 0 | 2/3424 (0.1%) | 2 |
| Premature Labour | 4/6848 (0.1%) | 4 | 2/3424 (0.1%) | 2 |
| Puerperal Pyrexia | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Stillbirth | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Psychiatric disorders | ||||
| Abnormal Behaviour | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Acute Psychosis | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Bipolar I Disorder | 0/6848 (0%) | 0 | 1/3424 (0%) | 2 |
| Bipolar Disorder | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Mental Disorder | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Psychosomatic Disease | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Psychotic Disorder | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Schizophrenia | 2/6848 (0%) | 2 | 1/3424 (0%) | 2 |
| Somatoform Disorder | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Suicide Attempt | 1/6848 (0%) | 1 | 2/3424 (0.1%) | 2 |
| Renal and urinary disorders | ||||
| Calculus Ureteric | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Glomerulonephritis Acute | 3/6848 (0%) | 3 | 1/3424 (0%) | 1 |
| Nephrotic Syndrome | 2/6848 (0%) | 4 | 0/3424 (0%) | 0 |
| Neurogenic Bladder | 0/6848 (0%) | 0 | 1/3424 (0%) | 3 |
| Post Streptococcal Glomerulonephritis | 9/6848 (0.1%) | 9 | 3/3424 (0.1%) | 3 |
| Renal Failure Acute | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Renal Tubular Acidosis | 1/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Reproductive system and breast disorders | ||||
| Acquired Phimosis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Breast Mass | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Dysfunctional Uterine Bleeding | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Endometriosis | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Haemorrhagic Ovarian Cyst | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Ovarian Cyst | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Ovarian Haemorrhage | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Uterine Cervical Erosion | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Uterine Haemorrhage | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Vaginal Haematoma | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Adenoidal Hypertrophy | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Asphyxia | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Asthma | 12/6848 (0.2%) | 19 | 9/3424 (0.3%) | 9 |
| Bronchial Hyperreactivity | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Nasal Polyps | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Nasal Septum Deviation | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Neonatal Asphyxia | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Pneumothorax | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Respiratory Acidosis | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Sleep Apnoea Syndrome | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Upper Respiratory Tract Inflammation | 2/6848 (0%) | 2 | 0/3424 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||
| Angioedema | 2/6848 (0%) | 2 | 1/3424 (0%) | 1 |
| Dermal Cyst | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Henoch-Schonlein Purpura | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Skin Hypertrophy | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Urticaria | 1/6848 (0%) | 1 | 2/3424 (0.1%) | 2 |
| Social circumstances | ||||
| Child Abuse | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Physical Assault | 4/6848 (0.1%) | 4 | 1/3424 (0%) | 1 |
| Victim Of Child Abuse | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Victim Of Crime | 1/6848 (0%) | 1 | 1/3424 (0%) | 1 |
| Victim Of Sexual Abuse | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Surgical and medical procedures | ||||
| Abortion Induced | 1/6848 (0%) | 1 | 0/3424 (0%) | 0 |
| Vascular disorders | ||||
| Aneurysm Ruptured | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Haematoma | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
| Hypertension | 0/6848 (0%) | 0 | 1/3424 (0%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| CYD Dengue Vaccine Group | Placebo Group | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 942/1334 (70.6%) | 453/663 (68.3%) | ||
| General disorders | ||||
| Asthenia | 378/1334 (28.3%) | 530 | 167/663 (25.2%) | 244 |
| Injection Site Erythema | 107/1334 (8%) | 142 | 52/663 (7.8%) | 71 |
| Injection Site Pain | 616/1334 (46.2%) | 994 | 275/663 (41.5%) | 449 |
| Injection Site Swelling | 68/1334 (5.1%) | 84 | 33/663 (5%) | 36 |
| Malaise | 476/1334 (35.7%) | 689 | 239/663 (36%) | 352 |
| Pyrexia | 267/1334 (20%) | 291 | 125/663 (18.9%) | 137 |
| Infections and infestations | ||||
| Nasopharyngitis | 85/1334 (6.4%) | 113 | 45/663 (6.8%) | 61 |
| Upper Respiratory Tract Infection | 95/1334 (7.1%) | 104 | 54/663 (8.1%) | 62 |
| Musculoskeletal and connective tissue disorders | ||||
| Myalgia | 414/1334 (31%) | 585 | 197/663 (29.7%) | 296 |
| Nervous system disorders | ||||
| Headache | 567/1334 (42.5%) | 866 | 264/663 (39.8%) | 409 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 63/1334 (4.7%) | 69 | 48/663 (7.2%) | 61 |
| Rhinorrhoea | 46/1334 (3.4%) | 48 | 36/663 (5.4%) | 43 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.
Results Point of Contact
| Name/Title | Medical Director |
|---|---|
| Organization | Sanofi Pasteur Inc. |
| Phone | |
| Contact-US@sanofi.com |
- CYD14
- UTN: U1111-1116-4957
- 2014-001708-24