Dengue VirusPhase 2NCT00842530
Efficacy and Safety of Dengue Vaccine in Healthy Children
A Phase 2 study testing CYD Dengue Vaccine and Inactivated rabies virus vaccine in people with Dengue Virus and Dengue Fever, run by Sanofi Pasteur, a Sanofi Company at 1 site in Thailand.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 4 to 11 yearsHealthy volunteers can take part
- Conditions the study is for
- Dengue Virus, Dengue Fever, Dengue Hemorrhagic Fever
- What is being tested?
- CYD Dengue Vaccine and Inactivated rabies virus vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4,002 participants
- Where
- 1 siteThailand
- Study dates
- Feb 2009to Feb 2014
- Phase
- Phase 2
- 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 4 to 11 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Aged 4 to 11 years on the day of inclusion.
- Participant in good health, based on medical history and physical examination.
- Provision of assent form signed by the participants (for participants >= 7 years old) and informed consent form signed by the parent or another legally acceptable representative.
- Participant and parent/ legally acceptable representative able to attend all scheduled visits and to comply with all trial procedures.
- Participant attended one of the schools involved in the trial and living in the Ratchaburi Province.
- For a female participant of child-bearing potential (girls post-menarche), avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks prior to first vaccination, until at least 4 weeks after the last vaccination.
Who cannot join
- Febrile illness (temperature >= 37.5°C) or moderate or severe acute illness/infection on the day of vaccination, according to Investigator judgment.
- For a female participant of child-bearing potential (girls post-menarche), known pregnancy or positive urine pregnancy test on the day of the first trial vaccination.
- Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
- Planned participation in another clinical trial during the present trial period.
- Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy, or long-term systemic corticosteroids therapy.
- Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccines or to a vaccine containing any of the same substances.
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- Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.
- Receipt of blood or blood-derived products in the past 3 months.
- Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
- Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.
- Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.
- Planned receipt of any vaccine in the 4 weeks following the first trial vaccination.e
- Participant who plans to attend another school (outside the trial area) or move to another city in the coming 30 months.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Efficacy and Safety of Dengue Vaccine in Healthy Children Aged 4 to 11 Years in Thailand
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:
Read more
- Vaccine efficacy against severe VCD cases
- Vaccine efficacy against VCD cases following at least two injections with CYD dengue vaccine
- Immune response to CYD dengue vaccine
- Safety profile of CYD dengue vaccine. Safety assessments include solicited reactions within 7 or 14 days after each injection, unsolicited adverse events within 28 days after each injection, and serious adverse events during the study period.
Other objectives included:
- Vaccine efficacy against VCD cases following at least one injection with CYD dengue vaccine
- Vaccine efficacy against VCD cases due to each serotype
- Participants with clinical signs and symptoms for VCD
Read the detailed description
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.
- Conditions
- Dengue Virus, Dengue Fever, Dengue Hemorrhagic Fever, Dengue Diseases
- Being tested
- CYD Dengue Vaccine, Inactivated rabies virus vaccine, Placebo
- Keywords
- Dengue virus, Dengue fever, Dengue hemorrhagic fever, Dengue diseases, Dengue vaccine
- 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.
CYD Dengue VaccineBiological
Also called Dengvaxia
0.5 mL, Subcutaneous
Inactivated rabies virus vaccineBiological
Also called Verorab®
0.5 mL, Subcutaneous
PlaceboBiological
Sodium chloride 0.9%
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: CYD Dengue Vaccine |
| 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. Receives: Biological: Inactivated rabies virus vaccine; Biological: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 14 days post-any Inj. and each of the 3 Inj.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2009 (estimated)
- Study startFeb 2009
- Primary completionSep 2013
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Dengue VirusStudies of the same condition, open and under way.
- More trials run by Sanofi Pasteur, a Sanofi CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 4,002 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi Pasteur, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi Pasteur, a Sanofi Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00842530
- Sponsor's protocol ID
- CYD23
- Other IDs
- 2014-001710-25, 2014
- Status last verified
- Mar 2022
- First submitted
- 11 Feb 2009
- Last updated
- 5 Apr 2022
- Results posted
- Yes, on ClinicalTrials.gov
- 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
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.
PubMed 23540847Forrat 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.
PubMed 33822015Sridhar 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 29897841Plennevaux 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.
PubMed 27102820Hadinegoro 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 26214039Sabchareon 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.
PubMed 22975340
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Dengue Vaccine in Healthy Children Aged 4 to 11 Years in Thailand
- ClinicalTrials.gov ID
- NCT00842530
- Acronym / sponsor ID
- CYD23
- Conditions
- Dengue Virus, Dengue Fever, Dengue Hemorrhagic Fever, Dengue Diseases
- Keywords
- Dengue virus, Dengue fever, Dengue hemorrhagic fever, Dengue diseases, Dengue vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4,002 participants (actual)
- Lead sponsor
- Sanofi Pasteur, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- Feb 2009 (actual)
- Primary completion
- Sep 2013 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 12 Feb 2009 (estimated)
- Results
- Posted 26 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Vaccine efficacy against severe VCD cases
- Vaccine efficacy against VCD cases following at least two injections with CYD dengue vaccine
- Immune response to CYD dengue vaccine
- Safety profile of CYD dengue vaccine. Safety assessments include solicited reactions within 7 or 14 days after each injection, unsolicited adverse events within 28 days after each injection, and serious adverse events during the study period.
Other objectives included:
- Vaccine efficacy against VCD cases following at least one injection with CYD dengue vaccine
- Vaccine efficacy against VCD cases due to each serotype
- Participants with clinical signs and symptoms for VCD
Detailed description
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CYD Dengue Vaccine Group | Experimental | Biological: CYD Dengue VaccineParticipants (both Cohort 1 and 2) received 3 injections of the CYD Dengue vaccine, 1 injection each at 0, 6, and 12 months. |
| Control Group | Placebo comparator | Biological: Inactivated rabies virus vaccine, Biological: PlaceboParticipants (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. |
Who may qualify
- Ages
- 4 to 11 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Aged 4 to 11 years on the day of inclusion.
- Participant in good health, based on medical history and physical examination.
- Provision of assent form signed by the participants (for participants >= 7 years old) and informed consent form signed by the parent or another legally acceptable representative.
- Participant and parent/ legally acceptable representative able to attend all scheduled visits and to comply with all trial procedures.
- Participant attended one of the schools involved in the trial and living in the Ratchaburi Province.
Key exclusion criteria (13 listed)
- Febrile illness (temperature >= 37.5°C) or moderate or severe acute illness/infection on the day of vaccination, according to Investigator judgment.
- For a female participant of child-bearing potential (girls post-menarche), known pregnancy or positive urine pregnancy test on the day of the first trial vaccination.
- Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
- Planned participation in another clinical trial during the present trial period.
- Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy, or long-term systemic corticosteroids therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CYD Dengue VaccineAlso: Dengvaxia0.5 mL, Subcutaneous | Biological | CYD Dengue Vaccine Group |
| Inactivated rabies virus vaccineAlso: Verorab®0.5 mL, Subcutaneous | Biological | Control Group |
| PlaceboSodium chloride 0.9% | Biological | Control Group |
Primary outcome
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
Time frame: 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)
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.
7 secondary outcomes
Number of Severe VCD Cases During the Active Phase Post-dose 3 Following Inj. With Either CYD Dengue Vaccine or a Placebo
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 14 days post-any Inj. and each of the 3 Inj.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23540847Sabchareon 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.
- Derived from this study: PubMed 33822015Forrat 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.
- Derived from this study: PubMed 29897841Sridhar 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.
- Derived from this study: PubMed 27102820Plennevaux 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.
- Derived from this study: PubMed 26214039Hadinegoro 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.
- Derived from this study: PubMed 22975340Sabchareon 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.
- Individual participant dataSharing planned: 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Sciences & Operations study director
Sanofi Pasteur, a Sanofi Company
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing CYD Dengue Vaccine and Inactivated rabies virus vaccine in people with Dengue Virus and Dengue Fever, run by Sanofi Pasteur, a Sanofi Company at 1 site in Thailand.
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 6 inclusion and 13 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 5 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Thailand. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 26 Jul 2019). 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 During the Active Phase Post-dose 3 Following Inj. With Either CYD Dengue Vaccine or a Placebo (time frame: 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)). 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 NCT00842530, which also lists 6 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 5 Apr 2022.