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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-001710-25 | EudraCT Number |
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The primary objective of the study was to assess the efficacy of CYD dengue vaccine after three injections in preventing symptomatic virologically-confirmed dengue (VCD) cases, regardless of the severity, due to any of the four serotypes in children aged 4 to 11 years at the time of inclusion.
Secondary objectives included to assess:
Other objectives included:
Participants (both cohort 1 and 2) received 3 injections of CYD dengue vaccine. Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (cohort 2) received placebo at 0, 6, and 12 months.
Dengue cases were collected for assessment of efficacy during the Active Phase from first injection until at least 13 months after the third injection. A subset of participants were also evaluated for reactogenicity and immunogenicity.
Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature >= 37.5°C measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue non-structural protein 1 (NS1) enzyme-linked immunosorbent assay antigen test, and occurring >28 days after the third injection.
Dengue hemorrhagic fever (DHF) Grade I, II, III, and IV according to the 1999 World Health Organization (WHO) definition:
Clinical Manifestations: a) Fever: acute onset, high and continuous, lasting 2 to 7 days. b) Any of the following hemorrhagic manifestations (including at least a positive tourniquet test): petechiae, purpura, ecchymosis, epistaxis, gum bleeding, and hematemesis and/or melena.
Laboratory Findings: c) thrombocytopenia (platelet count = 100 000/mm3 or less) d) Plasma leakage as shown by hemoconcentration (hematocrit increased by 20% or more) or pleural effusion (seen on chest X-ray) and/or hypoalbuminemia.
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. Grade IV: Profound shock with undetectable blood pressure and pulse.
Independent Data Monitoring Committee (IDMC) severity criteria:- 1) Thrombocytopenia: platelet count ≤ 50 000/mm^3 ; 2) Any hemorrhage that needs blood transfusion; 3) Objective evidence of capillary permeability documented by one or several of the following: a) Increase in hematocrit by >= 20 percent (%) compared to normal for age, or [(Maximum hematocrit - minimum hematocrit)/min]*100% >= 20%, b) Pleural or abdominal (ascites) effusion (diagnosed either by clinical signs or radiography or other imaging method), c) Hypoproteinemia; 4) Signs of circulatory failure manifested by: a) Narrow pulse pressure <20mm Hg, or hypotension for age (as defined by systolic pressure <80 mm Hg in children <5 years and systolic pressure < 90 mm Hg in children >= 5 years), and b) Rapid and weak pulse, and c) Signs of poor capillary perfusion (cold and clammy extremities, delayed capillary refill); 5) Visceral Manifestations such as: a) Neurological symptoms (convulsions or change in level of consciousness), b) Hepatic failure or elevation of hepatic enzyme (>5-fold normal level), c) Metabolic (hypoglycemia) or electrolyte (hyponatremia, hypocalcemia) disturbances or volume overload (acute pulmonary edema or congestive heart failure), d) Other visceral manifestations such as cardiomyopathy, acute renal failure, acute respiratory failure, cholecystitis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CYD Dengue Vaccine Group | Experimental | Participants (both Cohort 1 and 2) received 3 injections of the CYD Dengue vaccine, 1 injection each at 0, 6, and 12 months. |
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| Control Group | Placebo Comparator | Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (Cohort 2) received placebo at 0, 6, and 12 months. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CYD Dengue Vaccine | Biological | 0.5 mL, Subcutaneous |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Symptomatic Virologically-Confirmed Dengue (VCD) Cases During the Active Phase Post-dose 3 Following Inj. With Either CYD Dengue Vaccine or a Placebo | Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature >= 37.5 degree Celsius (°C) measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue non-structural protein-1 (NS1) enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk. | 28 days Post-Inj. 3 up to the end of Active Phase (up to 13 months Post-Inj. 3, i.e. up to 25 months) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Severe VCD Cases During the Active Phase Post-dose 3 Following Inj. With Either CYD Dengue Vaccine or a Placebo | The severity of VCD cases was assessed by WHO 1999 severity assessment and IDMC clinical assessment. Dengue Hemorrhagic Fever (DHF) Grade I, II, III, and IV : Clinical Manifestations: a) Fever: acute onset, high and continuous, lasting 2-7 days, b) Any of hemorrhagic manifestations: petechiae, purpura, ecchymosis, epistaxis, gum bleeding, and hematemesis and/or melena, c) thrombocytopenia (platelet count=100 000/mm3 or less) d) Plasma leakage as shown by hemoconcentration (hematocrit increased by 20% or more) or pleural effusion and/or hypoalbuminemia. IDMC severity criteria: 1) Thrombocytopenia: platelet count <= 50 000/mm^3; 2) Hemorrhage that needs blood transfusion; 3) Objective evidence of capillary permeability 4) Signs of circulatory failure; 5) Visceral Manifestations. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Symptomatic VCD Cases During the Active Phase Following at Least One Inj. With Either CYD Dengue Vaccine or a Placebo | Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature >=37.5°C measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk. |
Inclusion Criteria :
Exclusion Criteria :
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Sciences & Operations | Sanofi Pasteur, a Sanofi Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Sanofi Pasteur Investigational Site | Bangkok | 10400 | Thailand |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23540847 | Result | Sabchareon A, Wallace D, Lang J, Bouckenooghe A, Moureau A. Efficacy of tetravalent dengue vaccine in Thai schoolchildren - Authors' reply. Lancet. 2013 Mar 30;381(9872):1094-5. doi: 10.1016/S0140-6736(13)60755-2. No abstract available. | |
| 33822015 | Derived | Forrat R, Dayan GH, DiazGranados CA, Bonaparte M, Laot T, Capeding MR, Sanchez L, Coronel DL, Reynales H, Chansinghakul D, Hadinegoro SRS, Perroud AP, Frago C, Zambrano B, Machabert T, Wu Y, Luedtke A, Price B, Vigne C, Haney O, Savarino SJ, Bouckenooghe A, Noriega F. Analysis of Hospitalized and Severe Dengue Cases Over the 6 years of Follow-up of the Tetravalent Dengue Vaccine (CYD-TDV) Efficacy Trials in Asia and Latin America. Clin Infect Dis. 2021 Sep 15;73(6):1003-1012. doi: 10.1093/cid/ciab288. |
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Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org
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Two-step enrollment approach was followed. Cohort 1 (100 participants [CYD vaccine arm] received CYD vaccine as Injection [Inj.] 1 and 50 [control group arm] received rabies vaccine as Inj. 1) was enrolled first. After 14 days review of Cohort 1 safety data in both arms, cohort 2 was enrolled (2569 participants in CYD group; 1283 in control group).
Study participants were enrolled from 05 February 2009 to 05 February 2010 at 1 clinical site in Thailand. A total of 4002 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized; however, only 3997 participants received the first vaccination.
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| ID | Title | Description |
|---|---|---|
| FG000 | CYD Dengue Vaccine Group | Participants (both Cohort 1 and 2) received 3 injections of the CYD Dengue vaccine, 1 Inj. each at 0, 6 months, and 12 months. |
| FG001 | Control Group | Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (Cohort 2) received placebo at 0, 6, and 12 months. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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Safety analysis set included all participants who have received at least one injection and were analyzed according to the treatment received.
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| ID | Title | Description |
|---|---|---|
| BG000 | CYD Dengue Vaccine Group | Participants (both Cohort 1 and 2) received 3 injections of the CYD Dengue vaccine, 1 Inj. each at 0, 6 months, and 12 months. |
| BG001 | Control Group |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Symptomatic Virologically-Confirmed Dengue (VCD) Cases During the Active Phase Post-dose 3 Following Inj. With Either CYD Dengue Vaccine or a Placebo | Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature >= 37.5 degree Celsius (°C) measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue non-structural protein-1 (NS1) enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk. | Analysis was performed on Per-protocol analysis (PPA) set for efficacy which included participants with no protocol deviations. Participants with following protocol deviations were excluded: inclusion criteria not met or exclusion criteria met, randomization error, Inj. not performed, code breaking and delay between the inj. not respected. | Posted | Number | Cases | 28 days Post-Inj. 3 up to the end of Active Phase (up to 13 months Post-Inj. 3, i.e. up to 25 months) |
Adverse event data were collected from Day 0 (post-vaccination) up to 13 months Post-Inj. 3 (up to 25 months).
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 injection.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CYD Dengue Vaccine Group | Participants (both Cohort 1 and 2) received 3 injections of the CYD Dengue vaccine, 1 Inj. each at 0, 6, and 12 months. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tonsillectomy | Surgical and medical procedures | MedDRA 11.0 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache; Post-Any Injection | Nervous system disorders | MedDRA 11.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Medical Director | Sanofi Pasteur | Contact-US@sanofi.com |
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| ID | Term |
|---|---|
| D003715 | Dengue |
| D019595 | Severe Dengue |
| ID | Term |
|---|---|
| D000096724 | Mosquito-Borne Diseases |
| D000079426 | Vector Borne Diseases |
| D007239 | Infections |
| D001102 | Arbovirus Infections |
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| ID | Term |
|---|---|
| D053059 | Dengue Vaccines |
| ID | Term |
|---|---|
| D014765 | Viral Vaccines |
| D014612 | Vaccines |
| D001688 | Biological Products |
| D045424 | Complex Mixtures |
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The observer-blind design was chosen since the products have different appearances and could be recognized. The person who performed vaccinations knew which product was administered while neither the participant nor the Investigator in charge of safety evaluation knew which product was injected. To maintain the blind and minimize the potential bias, the control group used the same route and schedule as the study vaccine.
| Inactivated rabies virus vaccine | Biological | 0.5 mL, Subcutaneous |
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| Placebo | Biological | Sodium chloride 0.9% |
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| 28 days Post-Inj. 3 up to the end of Active Phase (up to 13 months Post-Inj. 3, i.e. up to 25 months) |
| Number of Symptomatic VCD Cases During the Active Phase Following at Least Two Inj. With Either CYD Dengue Vaccine or a Placebo | Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature >= 37.5°C measured at least twice with an interval of at least 4 hours), confirmed by dengue reverse transcriptase-polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk. | 28 days Post-Inj. 2 up to Inj. 3, 28 days Post-Inj. 2 up to end of Active Phase ( up to 25 months) |
| Geometric Mean Titers (GMTs) of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo | GMT of antibodies against each serotype with the parental dengue virus strain were assessed by the plaque reduction neutralization test (PRNT). | Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3 |
| GMTs of Antibodies Against Each Serotype With the Parental Dengue Virus Strain in Dengue-Immune Participants Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo | GMTs of antibodies against each serotype with the parental dengue virus strain were assessed by the PRNT. Dengue immune participants were defined as those participants with titers >= 10 (1/dilution) against at least one dengue serotype at baseline. | Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3 |
| GMTs of Antibodies Against Each Serotype With the Parental Dengue Virus Strain in Dengue Non-Immune Participants Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo | GMTs of antibodies against each serotype with the parental dengue virus strain were assessed by the PRNT. Dengue non-immune participants were defined as participants with titers < 10 (1/dilution) against all four dengue serotypes at baseline. | Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3 |
| Percentage of Participants With Solicited Inj. Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Solicited Inj. site reactions: Pain, Erythema, and Swelling. Pain: - Grade 1: easily tolerated, Grade 2: sufficiently discomforting to interfere with normal behavior or activities, Grade 3: incapacitating, unable to perform usual activities. Erythema and Swelling: - Grade 1: > 0.0 to < 2.5 cm, Grade 2: >= 2.5 to < 5 cm, Grade 3: >= 5 cm. | 7 days post-any Inj. and each of the 3 Inj. |
| Percentage of Participants With Solicited Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever:- Grade 1: >=37.5°C to <=38.0°C, Grade 2: >38.0°C to <=39.0°C, Grade 3: >39.0°C. Headache, malaise, myalgia and asthenia: - Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities. | 14 days post-any Inj. and each of the 3 Inj. |
| Day 0 (Post-Inj.) up to end of Active phase (up to 25 months); 28 days post-Inj. 1 up to end of Active phase (up to 25 months) |
| Number of Participants With One VCD Episode During the Active Phase Due to Each Serotypes Following Inj. With Either CYD Dengue Vaccine or a Placebo | Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature >= 37.5°C measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. VCD cases confirmed only by NS1 method were classified in the Not Identified category. Cases were defined as the number of participants with at least one symptomatic VCD episode more than 28 days after Inj. 3 (during the Active Phase). | After 28 days Post Inj. 3 up to the end of Active Phase (up to 25 months) |
| Mean Number of Days for Clinical Signs and Symptoms (Fever, Clinical Syndrome and Hospitalization) of VCD During the Active Phase Following Inj. With Either CYD Dengue Vaccine or a Placebo | Clinical signs and symptoms for VCD included the following: fever, clinical syndrome and hospitalization. Duration of each symptom (in days) is reported in this outcome measure. | Day 0 (Post-Inj.) up to end of Active Phase (up to 25 months) |
| Number of Participants Requiring Hospitalization for VCD During the Active Phase Following Inj. With Either CYD Dengue Vaccine or a Placebo | Day 0 (Post-Inj.) up to end of Active Phase (up to 25 months) |
| 29897841 | Derived | Sridhar S, Luedtke A, Langevin E, Zhu M, Bonaparte M, Machabert T, Savarino S, Zambrano B, Moureau A, Khromava A, Moodie Z, Westling T, Mascarenas C, Frago C, Cortes M, Chansinghakul D, Noriega F, Bouckenooghe A, Chen J, Ng SP, Gilbert PB, Gurunathan S, DiazGranados CA. Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy. N Engl J Med. 2018 Jul 26;379(4):327-340. doi: 10.1056/NEJMoa1800820. Epub 2018 Jun 13. |
| 27102820 | Derived | Plennevaux E, Sabchareon A, Limkittikul K, Chanthavanich P, Sirivichayakul C, Moureau A, Boaz M, Wartel TA, Saville M, Bouckenooghe A. Detection of dengue cases by serological testing in a dengue vaccine efficacy trial: Utility for efficacy evaluation and impact of future vaccine introduction. Vaccine. 2016 May 23;34(24):2707-12. doi: 10.1016/j.vaccine.2016.04.028. Epub 2016 Apr 18. |
| 26214039 | Derived | Hadinegoro SR, Arredondo-Garcia JL, Capeding MR, Deseda C, Chotpitayasunondh T, Dietze R, Muhammad Ismail HI, Reynales H, Limkittikul K, Rivera-Medina DM, Tran HN, Bouckenooghe A, Chansinghakul D, Cortes M, Fanouillere K, Forrat R, Frago C, Gailhardou S, Jackson N, Noriega F, Plennevaux E, Wartel TA, Zambrano B, Saville M; CYD-TDV Dengue Vaccine Working Group. Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease. N Engl J Med. 2015 Sep 24;373(13):1195-206. doi: 10.1056/NEJMoa1506223. Epub 2015 Jul 27. |
| 22975340 | Derived | Sabchareon A, Wallace D, Sirivichayakul C, Limkittikul K, Chanthavanich P, Suvannadabba S, Jiwariyavej V, Dulyachai W, Pengsaa K, Wartel TA, Moureau A, Saville M, Bouckenooghe A, Viviani S, Tornieporth NG, Lang J. Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial. Lancet. 2012 Nov 3;380(9853):1559-67. doi: 10.1016/S0140-6736(12)61428-7. Epub 2012 Sep 11. |
| Protocol Violation |
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| Lost to Follow-up |
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| Withdrawal by Subject |
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Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (Cohort 2) received placebo at 0, 6, and 12 months.
| BG002 | Total | Total of all reporting groups |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| ID | Title | Description |
|---|
| OG000 | CYD Dengue Vaccine Group | Participants (both Cohort 1 and 2) received 3 injections of the CYD Dengue vaccine, 1 Inj. each at 0, 6, and 12 months. |
| OG001 | Control Group | Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (Cohort 2) received placebo at 0, 6, and 12 months. |
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| Secondary | Number of Severe VCD Cases During the Active Phase Post-dose 3 Following Inj. With Either CYD Dengue Vaccine or a Placebo | The severity of VCD cases was assessed by WHO 1999 severity assessment and IDMC clinical assessment. Dengue Hemorrhagic Fever (DHF) Grade I, II, III, and IV : Clinical Manifestations: a) Fever: acute onset, high and continuous, lasting 2-7 days, b) Any of hemorrhagic manifestations: petechiae, purpura, ecchymosis, epistaxis, gum bleeding, and hematemesis and/or melena, c) thrombocytopenia (platelet count=100 000/mm3 or less) d) Plasma leakage as shown by hemoconcentration (hematocrit increased by 20% or more) or pleural effusion and/or hypoalbuminemia. IDMC severity criteria: 1) Thrombocytopenia: platelet count <= 50 000/mm^3; 2) Hemorrhage that needs blood transfusion; 3) Objective evidence of capillary permeability 4) Signs of circulatory failure; 5) Visceral Manifestations. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk. | Analysis was performed on PPA set for efficacy. | Posted | Number | Cases | 28 days Post-Inj. 3 up to the end of Active Phase (up to 13 months Post-Inj. 3, i.e. up to 25 months) |
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| Secondary | Number of Symptomatic VCD Cases During the Active Phase Following at Least Two Inj. With Either CYD Dengue Vaccine or a Placebo | Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature >= 37.5°C measured at least twice with an interval of at least 4 hours), confirmed by dengue reverse transcriptase-polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk. | Analysis was performed on Other Efficacy Analysis Set 2 which included all participants who received at least the two first injections. | Posted | Number | Cases | 28 days Post-Inj. 2 up to Inj. 3, 28 days Post-Inj. 2 up to end of Active Phase ( up to 25 months) |
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| Secondary | Geometric Mean Titers (GMTs) of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo | GMT of antibodies against each serotype with the parental dengue virus strain were assessed by the plaque reduction neutralization test (PRNT). | Analysis was performed on Full Analysis Set for Immunogenicity defined as the participants included in the subgroup for Immunogenicity assessment who have received at least one dose and who had a blood sample drawn after vaccination. Here, 'number analyzed' = participants with available data for each specified category. | Posted | Geometric Mean | 95% Confidence Interval | Titers (1/dilution) | Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3 |
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| Secondary | GMTs of Antibodies Against Each Serotype With the Parental Dengue Virus Strain in Dengue-Immune Participants Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo | GMTs of antibodies against each serotype with the parental dengue virus strain were assessed by the PRNT. Dengue immune participants were defined as those participants with titers >= 10 (1/dilution) against at least one dengue serotype at baseline. | Analysis was performed on Full Analysis Set for Immunogenicity. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Geometric Mean | 95% Confidence Interval | Titers (1/dilution) | Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3 |
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| Secondary | GMTs of Antibodies Against Each Serotype With the Parental Dengue Virus Strain in Dengue Non-Immune Participants Before and Following Inj. With Either CYD Dengue Vaccine or a Placebo | GMTs of antibodies against each serotype with the parental dengue virus strain were assessed by the PRNT. Dengue non-immune participants were defined as participants with titers < 10 (1/dilution) against all four dengue serotypes at baseline. | Analysis was performed on Full Analysis Set for Immunogenicity. Here, "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category. | Posted | Geometric Mean | 95% Confidence Interval | Titers (1/dilution) | Pre-Inj. 1, 2, and 3, 28 days Post-Inj. 1, 2 and 3 and 1 year Post-Inj. 3 |
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| Secondary | Percentage of Participants With Solicited Inj. Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Solicited Inj. site reactions: Pain, Erythema, and Swelling. Pain: - Grade 1: easily tolerated, Grade 2: sufficiently discomforting to interfere with normal behavior or activities, Grade 3: incapacitating, unable to perform usual activities. Erythema and Swelling: - Grade 1: > 0.0 to < 2.5 cm, Grade 2: >= 2.5 to < 5 cm, Grade 3: >= 5 cm. | Analysis was performed in the Reactogenicity Analysis Set, which included all participants who received at least one injection and were considered evaluable for reactogenicity. Here, 'number analyzed' = participants with available data for each specified category. | Posted | Number | Percentage of participants | 7 days post-any Inj. and each of the 3 Inj. |
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| Secondary | Percentage of Participants With Solicited Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo | Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever:- Grade 1: >=37.5°C to <=38.0°C, Grade 2: >38.0°C to <=39.0°C, Grade 3: >39.0°C. Headache, malaise, myalgia and asthenia: - Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities. | Analysis was performed on Reactogenicity Analysis Set. Here, 'number analyzed' = participants with available data for each specified category. | Posted | Number | Percentage of participants | 14 days post-any Inj. and each of the 3 Inj. |
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|
|
| Other Pre-specified | Number of Symptomatic VCD Cases During the Active Phase Following at Least One Inj. With Either CYD Dengue Vaccine or a Placebo | Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature >=37.5°C measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk. | Analysis was performed on Other Efficacy Analysis Set 1 which included participants who received at least the first injection. | Posted | Number | Cases | Day 0 (Post-Inj.) up to end of Active phase (up to 25 months); 28 days post-Inj. 1 up to end of Active phase (up to 25 months) |
|
|
|
|
| Other Pre-specified | Number of Participants With One VCD Episode During the Active Phase Due to Each Serotypes Following Inj. With Either CYD Dengue Vaccine or a Placebo | Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature >= 37.5°C measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. VCD cases confirmed only by NS1 method were classified in the Not Identified category. Cases were defined as the number of participants with at least one symptomatic VCD episode more than 28 days after Inj. 3 (during the Active Phase). | Analysis was performed on Other Efficacy Analysis Set 1. | Posted | Count of Participants | Participants | No | After 28 days Post Inj. 3 up to the end of Active Phase (up to 25 months) |
|
|
|
| Other Pre-specified | Mean Number of Days for Clinical Signs and Symptoms (Fever, Clinical Syndrome and Hospitalization) of VCD During the Active Phase Following Inj. With Either CYD Dengue Vaccine or a Placebo | Clinical signs and symptoms for VCD included the following: fever, clinical syndrome and hospitalization. Duration of each symptom (in days) is reported in this outcome measure. | Analysis was performed on Safety Analysis Set. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. | Posted | Mean | Standard Deviation | Days | Day 0 (Post-Inj.) up to end of Active Phase (up to 25 months) |
|
|
|
| Other Pre-specified | Number of Participants Requiring Hospitalization for VCD During the Active Phase Following Inj. With Either CYD Dengue Vaccine or a Placebo | Analysis was performed on Safety Analysis Set. Here, 'overall number of participants analyzed' signifies participants who were evaluable for this outcome measure. | Posted | Number | participants | Day 0 (Post-Inj.) up to end of Active Phase (up to 25 months) |
|
|
|
| 1 |
| 2,666 |
| 315 |
| 2,666 |
| 415 |
| 697 |
| EG001 | Control Group | Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (Cohort 2) received placebo at 0, 6, and 12 months. | 4 | 1,331 | 176 | 1,331 | 207 | 350 |
| Ovarian cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.0 | Non-systematic Assessment |
|
| T-cell lymphoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 11.0 | Non-systematic Assessment |
|
| Allergy to arthropod sting | Immune system disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Perineal laceration | Pregnancy, puerperium and perinatal conditions | MedDRA 11.0 | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Drowning | General disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Influenza like illness | General disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Balanitis | Reproductive system and breast disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Epididymitis | Reproductive system and breast disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Vaginal perforation | Reproductive system and breast disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Accidental exposure | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Animal bite | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Arthropod bite | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Blast injury | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Brain contusion | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Burns second degree | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Clavicle fracture | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Epiphyseal injury | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Eye injury | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Facial bones fracture | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Forearm fracture | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Foreign body trauma | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Hand fracture | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Head injury | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Joint dislocation | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Lower limb fracture | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Meniscus lesion | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Muscle rupture | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Road traffic accident | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Snake bite | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Tendon injury | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Traumatic haemorrhage | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Vulva injury | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Wound | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA 11.0 | Non-systematic Assessment |
|
| Phimosis | Congenital, familial and genetic disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Tonsillar hypertrophy | Respiratory, thoracic and mediastinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Idiopathic thrombocytopenic purpura | Blood and lymphatic system disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Lymphadenitis | Blood and lymphatic system disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Convulsion | Nervous system disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Epilepsy | Nervous system disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Febrile convulsion | Nervous system disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Partial seizures | Nervous system disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Aphthous stomatitis | Gastrointestinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Appendicitis perforated | Gastrointestinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Food poisoning | Gastrointestinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Gastritis | Gastrointestinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Haemorrhoids | Gastrointestinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Mouth cyst | Gastrointestinal disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Cystitis haemorrhagic | Renal and urinary disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Post streptococcal glomerulonephritis | Renal and urinary disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Urethral stenosis | Renal and urinary disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Angioedema | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Leukocytoclastic vasculitis | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Synovitis | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Hypoglycaemic seizure | Metabolism and nutrition disorders | MedDRA 11.0 | Non-systematic Assessment |
|
| Abscess limb | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Abscess of eyelid | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Acute sinusitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Acute tonsillitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Appendicitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Arthritis bacterial | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Bronchitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Bronchitis viral | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Bronchopneumonia | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Cellulitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Cellulitis of male external genital | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Cellulitis staphylococcal | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Croup infectious | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Cystitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Dengue fever | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Diarrhoea infectious | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Dysentery | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Exanthema subitum | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Gastroenteritis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Gastroenteritis viral | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Herpes zoster | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Infection | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Infectious mononucleosis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Influenza | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Lobar pneumonia | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Malaria | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Mumps | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Orchitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Otitis media acute | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Perianal abscess | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Periorbital cellulitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Pharyngotonsillitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Pneumonia bacterial | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Pneumonia influenzal | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Pyelonephritis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Pyoderma | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Rhinitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Septic shock | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Staphylococcal sepsis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Subcutaneous abscess | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Tonsillitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Typhus | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Urinary tract infection | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Varicella | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Respiratory syncytial virus infection | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Viral myositis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Viral pharyngitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Wound infection | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Injection site Pain; Post-Any | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Injection site Erythema; Post-Any Injection | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Injection site Swelling; Post-Any Injection | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Fever; Post-Any Injection | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Malaise; Post-Any Injection | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Asthenia; Post-Any Injection | General disorders | MedDRA 11.0 | Systematic Assessment |
|
| Myalgia; Post-Any Injection | Musculoskeletal and connective tissue disorders | MedDRA 11.0 | Systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Pharyngitis | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA 11.0 | Non-systematic Assessment |
|
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
| D014777 |
| Virus Diseases |
| D018177 | Flavivirus Infections |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006482 | Hemorrhagic Fevers, Viral |
| Vaccine efficacy of against severe VCD (WHO 1999) | Vaccine efficacy (%) | 50.3 | 2-Sided | 95 | -585 | 96.4 | Other | The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy. The CI was calculated using the exact method conditional on the total number of cases in both groups. The vaccine efficacy of the CYD dengue vaccine against severe VCD cases was considered significant if the lower bound of its 95% CI was greater than 0%. |
| Vaccine efficacy: 28 days Post-Inj. 2 up to end of Active Phase | Vaccine efficacy (%) | 35.3 | 2-Sided | 95 | 3.3 | 56.5 | Superiority | The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy. The CI was calculated using the exact method conditional on the total number of cases in both groups. The vaccine efficacy of the CYD dengue vaccine against severe VCD cases was considered significant only if the lower bound of its 95% CI was greater than 0%. |
| Dengue Virus Serotype 1; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 1; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 1; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 1; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 1; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 1; 1 year Post-Inj. 3 |
|
|
| Dengue Virus Serotype 2; Pre-Inj. 1 |
|
|
| Dengue Virus Serotype 2; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 2; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 2; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 2; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 2; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 2; 1 year Post-Inj. 3 |
|
|
| Dengue Virus Serotype 3; Pre-Inj. 1 |
|
|
| Dengue Virus Serotype 3; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 3; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 3; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 3; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 3; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 3; 1 year Post-Inj. 3 |
|
|
| Dengue Virus Serotype 4; Pre-Inj. 1 |
|
|
| Dengue Virus Serotype 4; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 4; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 4; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 4; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 4; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 4; 1 year Post-Inj. 3 |
|
|
| Dengue Virus Serotype 1; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 1; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 1; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 1; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 1; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 1; 1 year Post-Inj. 3 |
|
|
| Dengue Virus Serotype 2; Pre-Inj. 1 |
|
|
| Dengue Virus Serotype 2; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 2; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 2; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 2; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 2; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 2; 1 year Post-Inj. 3 |
|
|
| Dengue Virus Serotype 3; Pre-Inj. 1 |
|
|
| Dengue Virus Serotype 3; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 3; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 3; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 3; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 3; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 3; 1 year Post-Inj. 3 |
|
|
| Dengue Virus Serotype 4; Pre-Inj. 1 |
|
|
| Dengue Virus Serotype 4; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 4; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 4; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 4; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 4; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 4; 1 year Post-Inj. 3 |
|
|
| Dengue Virus Serotype 1; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 1; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 1; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 1; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 1; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 1; 1 year Post-Inj. 3 |
|
|
| Dengue Virus Serotype 2; Pre-Inj. 1 |
|
|
| Dengue Virus Serotype 2; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 2; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 2; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 2; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 2; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 2; 1 year Post-Inj. 3 |
|
|
| Dengue Virus Serotype 3; Pre-Inj. 1 |
|
|
| Dengue Virus Serotype 3; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 3; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 3; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 3; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 3; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 3; 1 year Post-Inj. 3 |
|
|
| Dengue Virus Serotype 4; Pre-Inj. 1 |
|
|
| Dengue Virus Serotype 4; Post-Inj. 1 |
|
|
| Dengue Virus Serotype 4; Pre-Inj. 2 |
|
|
| Dengue Virus Serotype 4; Post-Inj. 2 |
|
|
| Dengue Virus Serotype 4; Pre-Inj. 3 |
|
|
| Dengue Virus Serotype 4; Post-Inj. 3 |
|
|
| Dengue Virus Serotype 4; 1 year Post-Inj. 3 |
|
|
| Grade 3 Inj. site Pain; Post-Any Inj. |
|
|
| Inj. site Erythema; Post-Any Inj. |
|
|
| Grade 3 Inj. site Erythema; Post-Any Inj. |
|
|
| Inj. site Swelling; Post-Any Inj. |
|
|
| Grade 3 Inj. site Swelling; Post-Any Inj. |
|
|
| Inj. site Pain; Post-Inj. 1 |
|
|
| Grade 3 Inj. site Pain; Post-Inj. 1 |
|
|
| Inj. site Erythema; Post-Inj. 1 |
|
|
| Grade 3 Inj. site Erythema; Post-Inj. 1 |
|
|
| Inj. site Swelling; Post-Inj. 1 |
|
|
| Grade 3 Inj. site Swelling; Post-Inj. 1 |
|
|
| Inj. site Pain; Post-Inj. 2 |
|
|
| Grade 3 Inj. site Pain; Post-Inj. 2 |
|
|
| Inj. site Erythema; Post-Inj. 2 |
|
|
| Grade 3 Inj. site Erythema; Post-Inj. 2 |
|
|
| Inj. site Swelling; Post-Inj. 2 |
|
|
| Grade 3 Inj. site Swelling; Post-Inj. 2 |
|
|
| Inj. site Pain; Post-Inj. 3 |
|
|
| Grade 3 Inj. site Pain; Post-Inj. 3 |
|
|
| Inj. site Erythema; Post-Inj. 3 |
|
|
| Grade 3 Inj. site Erythema; Post-Inj. 3 |
|
|
| Inj. site Swelling; Post-Inj. 3 |
|
|
| Grade 3 Inj. site Swelling; Post-Inj. 3 |
|
|
| Grade 3 Fever: Post-Any Inj. |
|
|
| Headache: Post-Any Inj. |
|
|
| Grade 3 Headache: Post-Any Inj. |
|
|
| Malaise: Post-Any Inj. |
|
|
| Grade 3 Malaise: Post-Any Inj. |
|
|
| Myalgia: Post-Any Inj. |
|
|
| Grade 3 Myalgia: Post-Any Inj. |
|
|
| Asthenia: Post-Any Inj. |
|
|
| Grade 3 Asthenia: Post-Any Inj. |
|
|
| Fever: Post-Inj. 1 |
|
|
| Grade 3 Fever: Post-Inj. 1 |
|
|
| Headache: Post-Inj. 1 |
|
|
| Grade 3 Headache: Post-Inj. 1 |
|
|
| Malaise: Post-Inj. 1 |
|
|
| Grade 3 Malaise: Post-Inj. 1 |
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| Myalgia: Post-Inj. 1 |
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| Grade 3 Myalgia: Post-Inj. 1 |
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| Asthenia: Post-Inj. 1 |
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| Grade 3 Asthenia: Post-Inj. 1 |
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| Fever: Post-Inj. 2 |
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| Grade 3 Fever: Post-Inj. 2 |
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| Headache: Post-Inj. 2 |
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| Grade 3 Headache: Post-Inj. 2 |
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| Malaise: Post-Inj. 2 |
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| Grade 3 Malaise: Post-Inj. 2 |
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| Myalgia: Post-Inj. 2 |
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| Grade 3 Myalgia: Post-Inj. 2 |
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| Asthenia: Post-Inj. 2 |
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| Grade 3 Asthenia: Post-Inj. 2 |
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| Fever: Post-Inj. 3 |
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| Grade 3 Fever: Post-Inj. 3 |
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| Headache: Post-Inj. 3 |
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| Grade 3 Headache: Post-Inj. 3 |
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| Malaise: Post-Inj. 3 |
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| Grade 3 Malaise: Post-Inj. 3 |
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| Myalgia: Post-Inj. 3 |
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| Grade 3 Myalgia: Post-Inj. 3 |
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| Asthenia: Post-Inj. 3 |
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| Grade 3 Asthenia: Post-Inj. 3 |
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| Vaccine efficacy: Day 0 up to end of Active Phase | Vaccine efficacy (%) | 34.9 | 2-Sided | 95 | 6.7 | 54.3 | Other | The statistical methodology was based on the use of the two-sided 95% CI of the vaccine efficacy. The CI was calculated using the exact method conditional on the total number of cases in both groups. The vaccine efficacy of the CYD dengue vaccine against severe VCD cases was considered significant if the lower bound of its 95% CI was greater than 0%. |
| Dengue Virus Serotype 3 |
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| Dengue Virus Serotype 4 |
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| Not Identified |
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| Hospitalization |
|