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AzTrials

DenguePhase 3NCT01373281

Study of a Novel Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 14 Years in Asia

A Phase 3 study testing Live, attenuated, dengue serotype 1, 2, 3, 4 virus in people with Dengue and Dengue Fever, run by Sanofi Pasteur, a Sanofi Company at 12 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 2 to 14 yearsHealthy volunteers can take part
Conditions the study is for
Dengue, Dengue Fever, Dengue Hemorrhagic Fever
What is being tested?
Live, attenuated, dengue serotype 1, 2, 3, 4 virus
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
10,275 participants
Where
12 sitesin 5 countries
Study dates
3 Jun 2011to 21 Nov 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 14 years
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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
Show all 12Show fewer
  • 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.

Trial locations and contacts

12 sites in 5 countries.

12 sites in 5 countries

Indonesia3 sites

  • Study site

    Bandung, West Java, 40161

  • Study site

    Denpasar, Bali, 80114

  • Study site

    Jakarta, 10430

Other trials in Indonesia

Thailand3 sites

  • Study site

    Ban Pong, Changwat Ratchaburi, 70110

  • Study site

    Nai Muang, Changwat Kamphaeng Phet, 6200

  • Study site

    Photharam, Changwat Ratchaburi, 70120

Other trials in Thailand

Malaysia2 sites

  • Study site

    Kuala Lumpur, 50586

  • Study site

    Pulau Pinang, 10450

Other trials in Malaysia

Philippines2 sites

  • Study site

    Cebu City, 6000

  • Study site

    San Pablo, 4000

Other trials in Philippines

Vietnam2 sites

  • Study site

    Long Xuyen, An Giang

  • Study site

    Mỹ Tho, Tien Giang Province

Other trials in Vietnam

About this study

Official title: Efficacy and Safety of a Novel Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 14 Years in Asia

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:

Read more

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.
Read the 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.

Being tested
Live, attenuated, dengue serotype 1, 2, 3, 4 virus, Placebo: Sodium chloride (NaCl) 0.9%
Keywords
Dengue, Dengue fever, Dengue Hemorrhagic Fever, CYD dengue vaccine, Flavivirus
Medical subject headings
Dengue, Severe Dengue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Live, attenuated, dengue serotype 1, 2, 3, 4 virusBiological

    Also called CYD Dengue Vaccine

    0.5 mL, Subcutaneous

  • Placebo: Sodium chloride (NaCl) 0.9%Biological

    0.5 mL, Subcutaneous

Study groups in NCT01373281
Study groupRoleWhat they receive
Dengue Vaccine GroupExperimentalParticipants were to receive CYD dengue vaccine at 0, 6, and 12 months.
Receives: Biological: Live, attenuated, dengue serotype 1, 2, 3, 4 virus
Control GroupPlacebo comparatorParticipants were to receive a placebo vaccine at 0, 6, and 12 months.
Receives: Biological: Placebo: Sodium chloride (NaCl) 0.9%

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection (Inj.) With Either CYD Dengue Vaccine or a Placebo

    Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue reverse transcriptase polymerase chain reaction and/or dengue NS protein 1 antigen enzyme-linked immunosorbent assay. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Vaccine Group.

    Measured: 28 days and up to 13 months post-dose 3

Secondary outcomes (13)

  1. Geometric Mean Titers of Antibodies Against Each Serotype With the Parental Dengue Virus Strain Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo

    Geometric mean titers against each of the 4 serotypes of dengue virus strains were assessed using the plaque reduction neutralization test (PRNT) in a pre-defined subset of participants.

    Measured: Pre-injection 1, 28 days post Injections 2 and 3, 13 months (Visit 07) and 60 months (Visit 12) post-injection 3

  2. Percentage of Participants With Antibody Titers >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain Before and Following Inj. With CYD Dengue Vaccine or Placebo

    Percentage of participants with antibody titers >= 10 (1/Dil) against each serotypes of the dengue virus strains were assessed using PRNT in a pre-defined subset of participants.

    Measured: Pre-injection 1, 28 days post Injections 2 and 3, 13 months (V 07) and 60 months (V 12) post-injection 3

  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 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.

    Measured: 28 days post-injection 1 and up to 13 months post-injection 3

  4. Number of Symptomatic VCD Cases Due to Any Serotype 28 Days Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo

    Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue reverse transcriptase polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Vaccine Group.

    Measured: 28 days post-injection 2 and up to 13 months post-injection 3

  5. Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase in Either CYD Dengue Vaccine or Placebo Group

    Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature >=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue reverse transcriptase polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Vaccine Group.

    Measured: Day 0 up to 13 months post-injection 3

  6. Number of Symptomatic VCD Cases Meeting 1997 WHO Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo

    Dengue hemorrhagic fever cases were defined as number of participants with at least one symptomatic VCD episode meeting the 1997 WHO criteria.

    (a) Fever: acute onset, high (>= 38°C) and continuous, lasting 2 to 7 days and (b) any of the pre-listed hemorrhagic manifestations and laboratory findings of thrombocytopenia (platelet <=100 x 109/L) and plasma leakage as shown by hemoconcentation (hematocrit increased by 20% or more) or pleural effusion (seen on CXR) and/or ascites and/or hypoaluminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish a clinical diagnosis of DHF. Dengue hemorrhagic fever was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhage.

    Measured: Day 0 to the end of study (up to 72 months)

  7. Number of Symptomatic VCD Cases Meeting 1997 WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo

    The 1997 WHO criteria are: a) Fever: acute onset, high (>= 38°C) and continuous, for 2 to 7 days and (b) any of the following: thrombocytopenia (platelet <=100 x 109/L) and plasma leakage as shown by hematocrit increased by 20% or more or pleural effusion and/or ascites and/or hypoaluminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish diagnosis of DHF. Dengue hemorrhagic fever was graded as follows:Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test; Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participant,usually in the form of skin and/or other hemorrhages; Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness; and Grade IV: Profound shock with undetectable blood pressure and pulse.

    Measured: From consent to participate int the Surveillance Expansion Period to 60 months post-injection 3 (up to Month 72)

  8. Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo

    The severity of VCD cases was assessed by an IDMC based on a medical review of cases and any of the following criteria:1) Platelet count <=100000 μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure <= 20 mmHg in a child, or hypotension [<= 90 mmHg] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. Unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by GCS score 5) Liver impairment (AST >1000 IU/L or PT INR >1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine >= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.

    Measured: Day 0 to the end of study (up to 72 months)

  9. Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Inj. With Either CYD Dengue Vaccine or a Placebo

    The severity of VCD cases was assessed by an IDMC based on a medical review of cases and any of the following criteria:1) Platelet count <=100000μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure <= 20mmHg in a child, or hypotension [<= 90 mmHg] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. Unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by GCS score 5) Liver impairment (AST >1000 IU/L or PT INR >1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine >= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.

    Measured: From consent to participate in the Surveillance Expansion Period to 60 months post-injection 3 (up to Month 72)

  10. Number of Participants With Solicited Injection Site Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo

    Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 reactions (2-11 years): Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, >= 50 mm. Grade 3 Solicited injection site reactions (12-14 years): Pain, Significant, prevents daily activity; Erythema and Swelling, >100 mm.

    Measured: Within 7 days after injection

  11. Number of Participants With Systemic Reactions Following Any and Each Inj. With Either CYD Dengue Vaccine or a Placebo

    Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Asthenia. Grade 3 reactions: Fever, >= 39°C; Headache, Malaise, Myalgia, and Asthenia, Significant, prevents daily activity.

    Measured: Within 14 days after injection

  12. Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo

    Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS1 ELISA in participants with acute febrile illness (temperature >=38°C on at least 2 consecutive days) requiring hospitalization.

    Measured: Day 0 to the end of study (up to 72 months)

  13. Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo

    Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS1 ELISA in participants with acute febrile illness (temperature >= 38°C on at least 2 consecutive days) requiring hospitalization.

    Measured: From consent to participate in the Surveillance Expansion Period to 60 months post-injection 3 (up to Month 72)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Jun 2011 (estimated)
  2. Study start3 Jun 2011
  3. Primary completion1 Aug 2014
  4. Study completion21 Nov 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
10,275 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01373281
Sponsor's protocol ID
CYD14
Other IDs
UTN: U1111-1116-4957, 2014-001708-24, 2014
Status last verified
Mar 2022
First submitted
8 Jun 2011
Last updated
21 Mar 2022
Data monitoring committee
Yes
Individual data sharing
Yes: 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

Publications

  • Capeding MR, Tran NH, Hadinegoro SR, Ismail HI, Chotpitayasunondh T, Chua MN, Luong CQ, Rusmil K, Wirawan DN, Nallusamy R, Pitisuttithum P, Thisyakorn U, Yoon IK, van der Vliet D, Langevin E, Laot T, Hutagalung Y, Frago C, Boaz M, Wartel TA, Tornieporth NG, Saville M, Bouckenooghe A; CYD14 Study Group. Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial. Lancet. 2014 Oct 11;384(9951):1358-65. doi: 10.1016/S0140-6736(14)61060-6. Epub 2014 Jul 10.

    PubMed 25018116

  • 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.

    PubMed 27007959

  • Coudeville L, Baurin N, Vergu E. Estimation of parameters related to vaccine efficacy and dengue transmission from two large phase III studies. Vaccine. 2016 Dec 7;34(50):6417-6425. doi: 10.1016/j.vaccine.2015.11.023. Epub 2015 Nov 21.

    PubMed 26614588

  • 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.

    PubMed 26214039

  • Guy B, Jackson N. Dengue vaccine: hypotheses to understand CYD-TDV-induced protection. Nat Rev Microbiol. 2016 Jan;14(1):45-54. doi: 10.1038/nrmicro.2015.2. Epub 2015 Dec 7.

    PubMed 26639777

  • Gailhardou S, Skipetrova A, Dayan GH, Jezorwski J, Saville M, Van der Vliet D, Wartel TA. Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials. PLoS Negl Trop Dis. 2016 Jul 14;10(7):e0004821. doi: 10.1371/journal.pntd.0004821. eCollection 2016 Jul.

    PubMed 27414655

  • Vigne C, Dupuy M, Richetin A, Guy B, Jackson N, Bonaparte M, Hu B, Saville M, Chansinghakul D, Noriega F, Plennevaux E. Integrated immunogenicity analysis of a tetravalent dengue vaccine up to 4 y after vaccination. Hum Vaccin Immunother. 2017 Sep 2;13(9):2004-2016. doi: 10.1080/21645515.2017.1333211. Epub 2017 Jun 9.

    PubMed 28598256

  • Guy B, Noriega F, Ochiai RL, L'azou M, Delore V, Skipetrova A, Verdier F, Coudeville L, Savarino S, Jackson N. A recombinant live attenuated tetravalent vaccine for the prevention of dengue. Expert Rev Vaccines. 2017 Jul;16(7):1-13. doi: 10.1080/14760584.2017.1335201. Epub 2017 Jun 7.

    PubMed 28590795

  • Nealon J, Taurel AF, Capeding MR, Tran NH, Hadinegoro SR, Chotpitayasunondh T, Chong CK, Wartel TA, Beucher S, Frago C, Moureau A, Simmerman M, Laot T, L'Azou M, Bouckenooghe A. Symptomatic Dengue Disease in Five Southeast Asian Countries: Epidemiological Evidence from a Dengue Vaccine Trial. PLoS Negl Trop Dis. 2016 Aug 17;10(8):e0004918. doi: 10.1371/journal.pntd.0004918. eCollection 2016 Aug.

    PubMed 27532617

  • 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.

    PubMed 27418050

  • Coudeville L, Baurin N, L'Azou M, Guy B. Potential impact of dengue vaccination: Insights from two large-scale phase III trials with a tetravalent dengue vaccine. Vaccine. 2016 Dec 7;34(50):6426-6435. doi: 10.1016/j.vaccine.2016.08.050. Epub 2016 Sep 3.

    PubMed 27601343

  • 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.

    PubMed 29897841

  • 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.

    PubMed 35659904

  • 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:e65131. doi: 10.7554/eLife.65131.

    PubMed 34219653

  • 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.

    PubMed 34003796

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Live, attenuated, dengue serotype 1, 2, 3, 4 virus in people with Dengue and Dengue Fever, run by Sanofi Pasteur, a Sanofi Company at 12 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Indonesia, Thailand, Malaysia, Philippines, Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Nov 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 28 days and up to 13 months post-dose 3). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01373281, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Mar 2022.

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