Study of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America

Efficacy and Safety of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America

The aim of the study was to assess the efficacy of Sanofi Pasteur's CYD dengue vaccine in preventing symptomatic virologically-confirmed dengue cases for dengue-endemic areas of Latin America.

Primary Objective:

To assess the efficacy of CYD dengue vaccine after 3 vaccinations at 0, 6, and 12 months in preventing symptomatic virologically-confirmed dengue (VCD) cases, regardless of the severity, due to any of the four serotypes in children and adolescents aged 9 to 16 years at the time of inclusion.

Secondary Objectives:

• To describe the efficacy of CYD dengue vaccine in preventing symptomatic VCD cases after the third dose to the end of the Active Phase, after at least 1 dose, and after 2 doses.
• To describe the occurrence of hospitalized VCD cases and the occurrence of severe (clinically severe or as per World Health Organization (WHO) criteria) VCD cases, throughout the Surveillance Expansion Period (SEP) and throughout the trial (from Day 0 until the end of the study).
• To describe the antibody response to each dengue serotype after Dose 2, after Dose 3, and 1 and 5 years after Dose 3.
• To describe the occurrence of serious adverse events (SAEs), including SAEs of special interest in all participants throughout the trial period.

Study Overview

• Status: Completed
• Conditions: Dengue; Dengue Fever; Dengue Hemorrhagic Fever
• Intervention / Treatment: Biological: Live, attenuated, dengue serotype 1, 2, 3, 4 virus; Biological: Placebo: (NaCl) 0.9% solution

Detailed Description

Participants were randomized to either receive 3 injections of CYD dengue vaccine or a placebo at 0, 6, and 12 months.

A subset of participants from each country (N=2000) was also evaluated for reactogenicity and immunogenicity.

For each participant, the Active Phase of dengue case detection began after the first injection (Dose 1) and continued until 13 months after the third injection (Dose 3). It was assumed that 12 months of surveillance should result in the detection of a sufficient number of VCD cases to allow for an assessment of efficacy.

The Hospital Phase began after the Active Phase. Participants with a febrile illness and requiring hospitalization were screened for dengue until the end of the study.

Participants who consented to participate in the SEP were actively followed for dengue case detection (i.e. at least weekly contact and capturing any acute febrile illness, not just hospitalized febrile cases, as in the Active Phase). The SEP was designed to maximize the detection of symptomatic VCD (hospitalized or not) in order to describe CYD dengue vaccine efficacy and safety in preventing symptomatic dengue in the long-term. Participants who declined participating in the SEP continued surveillance as in the Hospital Phase until trial completion.

Symptomatic VCD cases occurring more than (>) 28 days after dose 3 (during the Active Phase) are defined as:

• Acute febrile illness (i.e. temperature >=38 degree Celsius (°C) on at least 2 consecutive days)
• Virologically confirmed by dengue Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) and/or dengue non-structural (NS)1 enzyme-linked immunosorbent assay (ELISA) Ag test.

Severity was assessed using a definition consistent with the 1997 WHO Classification Dengue Hemorrhagic Fever and by an independent Data Monitoring Committee (IDMC) severity criteria.

• Study Type: Interventional
• Enrollment (Actual): 20869
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • CE
    • Fortaleza, CE, Brazil, 60430 270
  • ES
    • Vitória, ES, Brazil, 29040 09
  • GO
    • Goiania, GO, Brazil, 74675 020
  • MS
    • Campo Grande, MS, Brazil, 79074 460
  • RN
    • Natal, RN, Brazil, 59025 600
• Colombia
  • Casanare
    • Aguazul, Casanare, Colombia
    • Yopal, Casanare, Colombia
  • Cundinamarca
    • Girardot, Cundinamarca, Colombia
  • Meta
    • Acacias, Meta, Colombia
  • Quindío
    • Armenia, Quindío, Colombia
    • Calarcá, Quindío, Colombia
    • La Tebaida, Quindío, Colombia
    • Montenegro, Quindío, Colombia
  • Santander
    • Bucaramanga, Santander, Colombia
• Honduras
  • Municipalidad Del Distrito Central
    • Tegucigalpa, Municipalidad Del Distrito Central, Honduras
• Mexico
  • Morelos
    • Temixco, Morelos, Mexico
  • Tamaulipas
    • Municipio De Cd. Mante, Tamaulipas, Mexico
  • Veracruz
    • Veracruz Puerto, Veracruz, Mexico
  • Yucatán
    • Tizimin, Yucatán, Mexico
    • Valladolid, Yucatán, Mexico
• Puerto Rico
  • Guayama, Puerto Rico, 00784
  • San Juan, Puerto Rico, 00918

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 12 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 9 to 16 years on the day of inclusion and resident of the site zone
• Participant in good health, based on medical history and physical examination
• Assent form or informed consent form has been signed and dated by the participant (based on local regulations), and informed consent form has been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations)
• Participant was able to attend all scheduled visits and comply with all trial procedures.

Exclusion Criteria:

• Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination).
• Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination
• Planned participation in another clinical trial during the present trial period
• Self-reported or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroids therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Self-reported seropositivity for Human Immunodeficiency Virus (HIV) infection
• Self-reported systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances
• Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion
• Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response
• Planned receipt of any vaccine in the 4 weeks following any trial vaccination
• Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily
• Current alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures
• Identified as a site employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as a family member (i.e., immediate, husband, wife and their children, adopted or natural) of the site employees or the Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CYD Dengue Vaccine Group; Participants were to receive 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Biological: Live, attenuated, dengue serotype 1, 2, 3, 4 virus; 0.5 mL, Subcutaneous; Other Names: CYD Dengue Vaccine
Placebo Comparator: Placebo Group; Participants were to receive a placebo vaccine at 0, 6, and 12 months.	Biological: Placebo: (NaCl) 0.9% solution; 0.5 mL, Subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection With Either CYD Dengue Vaccine or a Placebo	Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue reverse transcriptase polymerase chain reaction (RT-PCR) and/or dengue non-structural (NS) protein 1 antigen enzyme-linked immunosorbent assay (ELISA). Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.	28 days and up to 13 months post-injection 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase Following Injection With Either CYD Dengue Vaccine or a Placebo	Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.	Day 0 up to 13 months post-injection 3
Number of Symptomatic VCD Cases Due to Any Serotype Occurring 28 Days Post-dose 1 Following Injection With Either CYD Dengue Vaccine or a Placebo	Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.	28 days post-injection 1 and up to 13 months post-injection 3
Number of Symptomatic VCD Cases Due to Any Serotype Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo	Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.	28 days post-injection 2 and up to 13 months post-injection 3
Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo	Dengue hemorrhagic fever (DHF) cases were defined as number of participants with at least one symptomatic VCD episode meeting the 1997 WHO criteria. (a) Fever: acute onset, high (>= 38°C) and continuous, lasting 2 to 7 days and (b) any of the pre-listed hemorrhagic manifestations and laboratory findings of thrombocytopenia (platelet <=100 x 109/L) and plasma leakage as shown by hemoconcentration (hematocrit increased by 20% or more) or pleural effusion (seen on CXR) and/or ascites and/ or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish a clinical diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhage.	Day 0 to the end of study (up to 72 months)
Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo	The 1997 WHO criteria are: a) Fever: acute onset, high (>= 38°C) and continuous, for 2 to 7 days and (b) any of the following: thrombocytopenia (platelet <=100 x 109/L) and plasma leakage as shown by hematocrit increased by 20% or more or pleural effusion and/or ascites and/or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish diagnosis of DHF. DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participant, usually in the form of skin and/or other hemorrhages; Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness; and Grade IV: Profound shock with undetectable blood pressure and pulse.	From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)
Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo	Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature >=38°C on at least 2 consecutive days) requiring hospitalization.	Day 0 up to the end of study (up to 72 months)
Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo	Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature >=38°C on at least 2 consecutive days) requiring hospitalization.	From consent to participate in the Surveillance Expansion Period to end of the study (up to 72 months)
Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo	The severity of VCD cases was assessed by an Independent Data monitoring Committee (IDMC) based on a medical review of cases and any of the following criteria:1) Platelet count <=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure <= 20 mmHg in a child, or hypotension [<= 90 mmHg] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by Glasgow Coma Scale (GCS) score 5) Liver impairment (AST >1000 IU/L or prothrombin time [PT] International normalized ratio [INR] >1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine >= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.	Day 0 to the end of study (up to 72 months)
Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo	The severity of VCD cases was assessed by an IDMC based on a medical review of cases and any of the following criteria:-1) Platelet count <=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure <= 20 mmHg in a child, or hypotension [<= 90 mmHg] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. Unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by GCS score 5) Liver impairment (AST >1000 IU/L or PT INR >1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine >= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.	From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo	Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (parental strains) were measured by the plaque reduction neutralization test in a pre-defined subset of participants.	Pre-injection 1, 28 days post Injections 2 and 3, 13 months (Visit [V] 07) and 60 months (Visit [V] 12) post-injection 3
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo	Geometric mean titers for each of the 4 dengue virus serotypes (parental strains) were assessed using the plaque reduction neutralization test in a pre-defined subset of participants.	Pre-injection 1, 28 days post Injections 2 and 3, 13 months (V 07) and 60 months (V 12) post-injection 3
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo	Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 reactions (9-11 years): Pain: incapacitating, unable to perform usual activities; Erythema and Swelling, >= 50 mm. Grade 3 Solicited injection site reactions (12-16 years): Pain: significant, prevents daily activity; Erythema and Swelling, >100 mm.	Within 7 days after each and any injection
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo	Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Asthenia. Grade 3 reactions: Fever: >= 39°C; Headache, Malaise, Myalgia, and Asthenia: significant, prevents daily activity.	Within 14 days after each and any injection

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Villar L, Dayan GH, Arredondo-Garcia JL, Rivera DM, Cunha R, Deseda C, Reynales H, Costa MS, Morales-Ramirez JO, Carrasquilla G, Rey LC, Dietze R, Luz K, Rivas E, Miranda Montoya MC, Cortes Supelano M, Zambrano B, Langevin E, Boaz M, Tornieporth N, Saville M, Noriega F; CYD15 Study Group. Efficacy of a tetravalent dengue vaccine in children in Latin America. N Engl J Med. 2015 Jan 8;372(2):113-23. doi: 10.1056/NEJMoa1411037. Epub 2014 Nov 3.
• 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.
• Arredondo-Garcia JL, Hadinegoro SR, Reynales H, Chua MN, Rivera Medina DM, Chotpitayasunondh T, Tran NH, Deseda CC, Wirawan DN, Cortes Supelano M, Frago C, Langevin E, Coronel D, Laot T, Perroud AP, Sanchez L, Bonaparte M, Limkittikul K, Chansinghakul D, Gailhardou S, Noriega F, Wartel TA, Bouckenooghe A, Zambrano B; CYD-TDV Dengue Vaccine Study Group. Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America. Clin Microbiol Infect. 2018 Jul;24(7):755-763. doi: 10.1016/j.cmi.2018.01.018. Epub 2018 Feb 8.
• L'Azou M, Moureau A, Sarti E, Nealon J, Zambrano B, Wartel TA, Villar L, Capeding MR, Ochiai RL; CYD14 Primary Study Group; CYD15 Primary Study Group. Symptomatic Dengue in Children in 10 Asian and Latin American Countries. N Engl J Med. 2016 Mar 24;374(12):1155-66. doi: 10.1056/NEJMoa1503877.
• 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.
• Savarino SJ, Bonaparte M, Wang H, Dayan GH, Forrat R, Zhu M, Hodge S, Ataman-Onal Y, DiazGranados CA. Accuracy and efficacy of pre-dengue vaccination screening for previous dengue infection with a new dengue rapid diagnostic test: a retrospective analysis of phase 3 efficacy trials. Lancet Microbe. 2022 Jun;3(6):e427-e434. doi: 10.1016/S2666-5247(22)00033-7. Epub 2022 May 4.
• Laydon DJ, Dorigatti I, Hinsley WR, Nedjati-Gilani G, Coudeville L, Ferguson NM. Efficacy profile of the CYD-TDV dengue vaccine revealed by Bayesian survival analysis of individual-level phase III data. Elife. 2021 Jul 2;10. pii: e65131. doi: 10.7554/eLife.65131.
• Henein S, Adams C, Bonaparte M, Moser JM, Munteanu A, Baric R, de Silva AM. Dengue vaccine breakthrough infections reveal properties of neutralizing antibodies linked to protection. J Clin Invest. 2021 Jul 1;131(13):e147066. doi: 10.1172/JCI147066.
• 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.
• DiazGranados CA, Bonaparte M, Wang H, Zhu M, Lustig Y, Schwartz E, Forrat R, Dayan GH, Hodge S, Ataman-Onal Y, Savarino SJ. Accuracy and efficacy of pre-dengue vaccination screening for previous dengue infection with five commercially available immunoassays: a retrospective analysis of phase 3 efficacy trials. Lancet Infect Dis. 2021 Apr;21(4):529-536. doi: 10.1016/S1473-3099(20)30695-2. Epub 2020 Nov 16.
• Reynales H, Carrasquilla G, Zambrano B, Cortes S M, Machabert T, Jing J, Pallardy S, Haney O, Faccini M, Quintero J, Noriega F. Secondary Analysis of the Efficacy and Safety Trial Data of the Tetravalent Dengue Vaccine in Children and Adolescents in Colombia. Pediatr Infect Dis J. 2020 Apr;39(4):e30-e36. doi: 10.1097/INF.0000000000002580.
• Plennevaux E, Moureau A, Arredondo-Garcia JL, Villar L, Pitisuttithum P, Tran NH, Bonaparte M, Chansinghakul D, Coronel DL, L'Azou M, Ochiai RL, Toh ML, Noriega F, Bouckenooghe A. Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials. Clin Infect Dis. 2018 Apr 3;66(8):1164-1172. doi: 10.1093/cid/cix966.
• Rabaa MA, Girerd-Chambaz Y, Duong Thi Hue K, Vu Tuan T, Wills B, Bonaparte M, van der Vliet D, Langevin E, Cortes M, Zambrano B, Dunod C, Wartel-Tram A, Jackson N, Simmons CP. Genetic epidemiology of dengue viruses in phase III trials of the CYD tetravalent dengue vaccine and implications for efficacy. Elife. 2017 Sep 5;6:e24196. doi: 10.7554/eLife.24196.
• Harenberg A, de Montfort A, Jantet-Blaudez F, Bonaparte M, Boudet F, Saville M, Jackson N, Guy B. Cytokine Profile of Children Hospitalized with Virologically-Confirmed Dengue during Two Phase III Vaccine Efficacy Trials. PLoS Negl Trop Dis. 2016 Jul 26;10(7):e0004830. doi: 10.1371/journal.pntd.0004830. eCollection 2016 Jul.
• Olivera-Botello G, Coudeville L, Fanouillere K, Guy B, Chambonneau L, Noriega F, Jackson N; CYD-TDV Vaccine Trial Group. Tetravalent Dengue Vaccine Reduces Symptomatic and Asymptomatic Dengue Virus Infections in Healthy Children and Adolescents Aged 2-16 Years in Asia and Latin America. J Infect Dis. 2016 Oct 1;214(7):994-1000. doi: 10.1093/infdis/jiw297. Epub 2016 Jul 14.

Helpful Links

• Related Info
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Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2011
• Primary Completion (Actual): November 1, 2014
• Study Completion (Actual): March 5, 2018

Study Registration Dates

• First Submitted: June 14, 2011
• First Submitted That Met QC Criteria: June 15, 2011
• First Posted (Estimate): June 16, 2011

Study Record Updates

• Last Update Posted (Actual): March 21, 2022
• Last Update Submitted That Met QC Criteria: March 10, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Dengue Hemorrhagic Fever; Dengue Virus; Flavivirus; Dengue fever; CYD dengue vaccine; Dengue Disease
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Wounds and Injuries; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever; Hemorrhagic Fevers, Viral; Dengue; Severe Dengue; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: CYD15; UTN: U1111-1116-4986 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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