Dengue FeverPhase 2NCT00880893

Study of Sanofi Pasteur's CYD Dengue Vaccine in Healthy Subjects in Singapore

A Phase 2 study testing CYD Dengue vaccine and NaCl + influenza virus or hepatitis A vaccine in people with Dengue Fever and Dengue Hemorrhagic Fever, run by Sanofi Pasteur, a Sanofi Company at 5 sites in Singapore.

Completed

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

Official record

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Trial summary

Primary Objectives: To evaluate safety after each CYD Dengue vaccination in terms of injection site and systemic reactogenicity. To evaluate the occurrence of Serious Adverse Events (SAEs) throughout the trial period. Read more about this study

Who is it for?: Ages 2 to 45 yearsHealthy volunteers can take part
Conditions the study is for: Dengue Fever, Dengue Hemorrhagic Fever, Dengue Virus
What is being tested?: CYD Dengue vaccine and NaCl + influenza virus or hepatitis A vaccine
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,198 participants
Where: 5 sitesSingapore
Study dates: 7 Apr 2009to 14 Oct 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 2 to 45 years
All sexes
Healthy volunteers accepted
Child, Adult

Who may be able to join

Aged from 2 to 45 years on the day of inclusion.
Participant in good health, based on medical history and physical examination.
Provision of informed consent form (and assent form for participants aged 6 to 12 years) signed by the participant and by the parent(s) or another legally acceptable representative for participants aged less than 21 years.
Participants and parent(s)/legally acceptable representative able to attend all scheduled visits and comply with all trial procedures.
For a woman of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks before the first vaccination until 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 the first vaccination, according to Investigator judgment.
For a woman of child-bearing potential, known pregnancy or positive urine pregnancy test on the day of inclusion.
Breast-feeding woman.
Known systemic hypersensitivity to any of the components of the trial vaccines (especially egg proteins or neomycin) or history of a life-threatening reaction to the trial vaccines or to a vaccine containing any of the same substances.
Personal or family history of thymic pathology or myasthenia.
Previous hepatitis A vaccination (for children only).

Show all 16Show fewer

Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the past 6 months, or long-term systemic corticosteroid therapy.
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 that might interfere with the assessment of immune response.
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 18 coming months.
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.
Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
Current or past alcohol abuse or drug addiction that may interfere with the participants ability to comply with trial procedures.
Participant who plans to move to another country within the 18 coming months.

Trial locations and contacts

5 sites in 1 country.

City, postcode or hospital

5 sites in 1 country

Singapore5 sites

Study site
Singapore, 119074
Study site
Singapore, 169608
Study site
Singapore, 229899
Study site
Singapore, 308433
Study site
Singapore, 529889

Other trials in Singapore

About this study

Official title: Immunogenicity and Large-Scale Safety of Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Singapore

Primary Objectives:

To evaluate safety after each CYD Dengue vaccination in terms of injection site and systemic reactogenicity.
To evaluate the occurrence of Serious Adverse Events (SAEs) throughout the trial period.
To evaluate the humoral immune response to each CYD Dengue serotype after each vaccination in a subset of participants.

Secondary Objectives:

To evaluate the persistence of the humoral immune response during 4 years after the last vaccination in a subset of participants.

Read the detailed description

This was a multicenter trial involving three vaccinations one each at 0, 6 and 12 months over a period of 1 year, and a 4-year follow-up following the last vaccination.

Conditions: Dengue Fever, Dengue Hemorrhagic Fever, Dengue Virus, Dengue Diseases
Being tested: CYD Dengue vaccine, NaCl + influenza virus or hepatitis A vaccine
Keywords: Dengue virus, Dengue fever, Dengue Hemorrhagic fever, Dengue diseases, Sanofi Pasteur's CYD 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 Sanofi Pasteur's CYD Dengue Vaccine
0.5 mL, Subcutaneous on Day 0, Months 6 and 12
NaCl + influenza virus or hepatitis A vaccineBiological
Also called NaCl 0.9%, Vaxigrip®, Havrix® pediatric formulation
0.5 mL, Subcutaneous (Intramuscular - Hepatitis A)

Study groups in NCT00880893
Study group	Role	What they receive
CYD Dengue Vaccine Group	Experimental	Participant's received the CYD Dengue Vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. Receives: Biological: CYD Dengue vaccine
Placebo Group	Sham comparator	All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >= 12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations. Receives: Biological: NaCl + influenza virus or hepatitis A vaccine

What is being measured

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

Percentage of All Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Injection With CYD Dengue Vaccine or Placebo
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions (2-11 years): Pain, incapacitating, unable to perform usual activities; Erythema and Swelling, >=5 cm. Grade 3 Solicited injection site reactions (adolescents and adults: >=12 years): Pain, significant; prevents daily activity; Erythema and Swelling: >10 cm. Grade 3 Solicited systemic reactions (all participants): Fever, >=39.0°C; Headache, Malaise, Myalgia, and Asthenia: significant; prevents daily activity.
Measured: Day 0 up to 14 days post-any and each injection
Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Reporting Solicited Injection-site and Systemic Reactions Following Each Injection (Inj.) With CYD Dengue Vaccine or Placebo
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia.
Measured: Day 0 up to 14 days post-each injection
Percentage of All Participants Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against each dengue virus serotype (parental strains) was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
Measured: Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3
Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against each dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
Measured: Pre-Injection 1 and 28 days Post-Injection 3
Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
Measured: Pre-Injection 1 and 28 days Post-Injection 3
Geometric Mean Titers (GMTs) of Antibodies in All Participants Against Each Serotype With the Parental Dengue Virus Strain Before and Following Each Vaccination With CYD Dengue Vaccine or Placebo
GMTs against each serotype with the parental dengue virus strains were assessed using a dengue PRNT assay.
Measured: Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3
GMTs of Antibodies by Age Groups (2-11 Years, 12-17 Years, 18-45 Years) Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine
GMTs against each dengue virus serotype (parental strains) were assessed using a dengue PRNT assay.
Measured: Pre-Injection 1 and 28 days Post-Injection 3

Secondary outcomes (15)

Percentage of Participants Aged 2 to 11 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against each dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
Measured: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against each dengue virus serotypes (parental stains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with antibody titers >=10 (1/dilution).
Measured: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants Aged 18 to 45 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against each dengue virus serotypes (parental stains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
Measured: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants Aged 2 to 11 Years Old Who Achieved Seropositivity Against At Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
Measured: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
Measured: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants Aged 18 to 45 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
Measured: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
GMTs of Antibodies in Participants 2 to 11 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine
GMTs against each serotype with the dengue virus strain (parental strains) were assessed using a dengue PRNT assay.
Measured: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
GMTs of Antibodies in Participants 12 to 17 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo
GMTs against each serotype with the dengue virus strain (parental strains) were assessed using a dengue PRNT assay.
Measured: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
GMTs of Antibodies in Participants 18 to 45 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo
GMTs against each serotype with the dengue virus strain were assessed using a dengue PRNT assay.
Measured: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 2 to 11 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with antibody titers >=10 (1/dilution). Dengue participants immune at baseline was defined as those participants with titers >=10 (1/dilution) against at least one dengue serotype at baseline.
Measured: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 2 to 11 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants naïve at baseline was defined as those participants with titers <10 (1/dilution) against all dengue serotypes at baseline.
Measured: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 12 to 17 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants immune at baseline was defined as those participants with titers >=10 (1/dilution) against at least one dengue serotype at baseline.
Measured: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 12 to 17 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against each serotype with the dengue virus strain were assessed using a PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants naïve at baseline was defined as those participants with titers <10 (1/dilution) against all dengue serotypes at baseline.
Measured: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 18 to 45 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants immune at baseline was defined as those participants with titers >=10 (1/dilution) against at least one dengue serotype at baseline.
Measured: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 18 to 45 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants naïve at baseline was defined as those participants with titers <10 (1/dilution) against all dengue serotypes at baseline.
Measured: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

Timeline

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

7 Apr 200914 Oct 2014

First posted14 Apr 2009 (estimated)
Study start7 Apr 2009
Primary completionOct 2014
Study completion14 Oct 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 (2)Papers the sponsor has linked to this study.
Other trials for Dengue FeverStudies 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: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 1,198 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00880893
Sponsor's protocol ID: CYD28
Other IDs: 2014-001713-26, 2014
Status last verified: Mar 2022
First submitted: 13 Apr 2009
Last updated: 21 Mar 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

Harenberg A, Begue S, Mamessier A, Gimenez-Fourage S, Ching Seah C, Wei Liang A, Li Ng J, Yun Toh X, Archuleta S, Wilder-Smith A, Shek LP, Wartel-Tram A, Bouckenooghe A, Lang J, Crevat D, Caillet C, Guy B. Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore. Hum Vaccin Immunother. 2013 Nov;9(11):2317-25. doi: 10.4161/hv.25562. Epub 2013 Jul 9.
PubMed 23839107
Leo YS, Wilder-Smith A, Archuleta S, Shek LP, Chong CY, Leong HN, Low CY, Oh ML, Bouckenooghe A, Wartel TA, Crevat D. Immunogenicity and safety of recombinant tetravalent dengue vaccine (CYD-TDV) in individuals aged 2-45 y: Phase II randomized controlled trial in Singapore. Hum Vaccin Immunother. 2012 Sep;8(9):1259-71. doi: 10.4161/hv.21224. Epub 2012 Aug 16.
PubMed 22894958

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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A Study to Evaluate V181 Dengue Vaccine in Healthy Participants 2 to 17 Years of Age (V181-005/MOBILIZE-1)
Healthy
RecruitingPhase 1
Phase 1 Challenge Study Using rDEN2delta30-7169 to Evaluate Host-Pathogen Interactions in Primary, Homotypic, and Heterotypic Dengue Virus Infection
Healthy Volunteers, Dengue
Active, not recruiting
A Controlled Human Infection Model of Dengue
Dengue
RecruitingPhase 2/3
Emetine for Viral Outbreaks (a.k.a. EVOLVE Antiviral Initiative)
Dengue
RecruitingPhase 2
Adaptive Dengue Antiviral Platform Trial
Dengue, Antiviral Drugs

All Dengue Fever trials

Study at a glance

From the registry record, last updated by the sponsor on 21 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Immunogenicity and Large-Scale Safety of Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Singapore
ClinicalTrials.gov ID: NCT00880893
Acronym / sponsor ID: CYD28
Conditions: Dengue Fever, Dengue Hemorrhagic Fever, Dengue Virus, Dengue Diseases
Keywords: Dengue virus, Dengue fever, Dengue Hemorrhagic fever, Dengue diseases, Sanofi Pasteur's CYD Dengue Vaccine
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,198 participants (actual)
Lead sponsor: Sanofi Pasteur, a Sanofi CompanyIndustry (pharma, biotech, devices)
Study start: 7 Apr 2009 (actual)
Primary completion: Oct 2014 (actual)
Study completion: 14 Oct 2014 (actual)
First posted: 14 Apr 2009 (estimated)
Results: Posted 29 Jul 2019

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Primary Objectives:

To evaluate safety after each CYD Dengue vaccination in terms of injection site and systemic reactogenicity.
To evaluate the occurrence of Serious Adverse Events (SAEs) throughout the trial period.
To evaluate the humoral immune response to each CYD Dengue serotype after each vaccination in a subset of participants.

Secondary Objectives:

To evaluate the persistence of the humoral immune response during 4 years after the last vaccination in a subset of participants.

Detailed description

This was a multicenter trial involving three vaccinations one each at 0, 6 and 12 months over a period of 1 year, and a 4-year follow-up following the last vaccination.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
CYD Dengue Vaccine Group	Experimental	Biological: CYD Dengue vaccineParticipant's received the CYD Dengue Vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.
Placebo Group	Sham comparator	Biological: NaCl + influenza virus or hepatitis A vaccineAll participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >= 12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.

Who may qualify

Ages: 2 to 45 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (5 listed)

Aged from 2 to 45 years on the day of inclusion.
Participant in good health, based on medical history and physical examination.
Provision of informed consent form (and assent form for participants aged 6 to 12 years) signed by the participant and by the parent(s) or another legally acceptable representative for participants aged less than 21 years.
Participants and parent(s)/legally acceptable representative able to attend all scheduled visits and comply with all trial procedures.
For a woman of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks before the first vaccination until 4 weeks after the last vaccination.

Key exclusion criteria (16 listed)

Febrile illness (temperature >= 37.5°C) or moderate or severe acute illness/infection on the day of the first vaccination, according to Investigator judgment.
For a woman of child-bearing potential, known pregnancy or positive urine pregnancy test on the day of inclusion.
Breast-feeding woman.
Known systemic hypersensitivity to any of the components of the trial vaccines (especially egg proteins or neomycin) or history of a life-threatening reaction to the trial vaccines or to a vaccine containing any of the same substances.
Personal or family history of thymic pathology or myasthenia.

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: Sanofi Pasteur's CYD Dengue Vaccine0.5 mL, Subcutaneous on Day 0, Months 6 and 12	Biological	CYD Dengue Vaccine Group
NaCl + influenza virus or hepatitis A vaccineAlso: NaCl 0.9%, Vaxigrip®, Havrix® pediatric formulation0.5 mL, Subcutaneous (Intramuscular - Hepatitis A)	Biological	Placebo Group

Primary outcome

Percentage of All Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Injection With CYD Dengue Vaccine or Placebo
Time frame: Day 0 up to 14 days post-any and each injection
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions (2-11 years): Pain, incapacitating, unable to perform usual activities; Erythema and Swelling, >=5 cm. Grade 3 Solicited injection site reactions (adolescents and adults: >=12 years): Pain, significant; prevents daily activity; Erythema and Swelling: >10 cm. Grade 3 Solicited systemic reactions (all participants): Fever, >=39.0°C; Headache, Malaise, Myalgia, and Asthenia: significant; prevents daily activity.
Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Reporting Solicited Injection-site and Systemic Reactions Following Each Injection (Inj.) With CYD Dengue Vaccine or Placebo
Time frame: Day 0 up to 14 days post-each injection
Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia.
Percentage of All Participants Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3
Seropositivity against each dengue virus serotype (parental strains) was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1 and 28 days Post-Injection 3
Seropositivity against each dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1 and 28 days Post-Injection 3
Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
Geometric Mean Titers (GMTs) of Antibodies in All Participants Against Each Serotype With the Parental Dengue Virus Strain Before and Following Each Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3
GMTs against each serotype with the parental dengue virus strains were assessed using a dengue PRNT assay.
GMTs of Antibodies by Age Groups (2-11 Years, 12-17 Years, 18-45 Years) Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine
Time frame: Pre-Injection 1 and 28 days Post-Injection 3
GMTs against each dengue virus serotype (parental strains) were assessed using a dengue PRNT assay.

15 secondary outcomes

Percentage of Participants Aged 2 to 11 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants Aged 18 to 45 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants Aged 2 to 11 Years Old Who Achieved Seropositivity Against At Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants Aged 18 to 45 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
GMTs of Antibodies in Participants 2 to 11 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine
Time frame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
GMTs of Antibodies in Participants 12 to 17 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
GMTs of Antibodies in Participants 18 to 45 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 2 to 11 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 2 to 11 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 12 to 17 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 12 to 17 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 18 to 45 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Percentage of Participants (Aged 18 to 45 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
Time frame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

Results and safety

Results posted to the registry on 29 Jul 2019, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
CYD Dengue Vaccine Group	898	791
Placebo Group	300	255

Primary outcome: Percentage of All Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Injection With CYD Dengue Vaccine or Placebo

Time frame: Day 0 up to 14 days post-any and each injection. Number. Unit: Percentage of participants

Measure	CYD Dengue Vaccine Group n = 898	Placebo Group n = 300
Injection site Pain; Post-Any Injection	53.9	66.7
Grade 3 Injection site Pain; Post-Any Injection	1.0	2.0
Injection site Erythema; Post-Any Injection	7.2	15.2
Grade 3 Inj. site Erythema; Post-Any Inj.	0.0	0.0
Injection site Swelling; Post-Any Injection	4.1	8.4
Grade 3 Inj. site Swelling; Post-Any Inj.	0.0	0.0
Injection site Pain; Post-Injection 1	31.3	21.9
Grade 3 Injection site Pain; Post- Injection 1	0.3	0.7

Population analysed: Analysis was performed on Safety analysis set. Here, 'number analyzed' = participants with available data for each specified category.

Primary outcome: Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Reporting Solicited Injection-site and Systemic Reactions Following Each Injection (Inj.) With CYD Dengue Vaccine or Placebo

Time frame: Day 0 up to 14 days post-each injection. Number. Unit: Percentage of participants

Measure	CYD Dengue Vaccine Group n = 898	Placebo Group n = 300
2-11 years; Injection site Pain, Post-Inj. 1	33.9	30.0
2-11 years; Inj. site Erythema, Post-Inj. 1	6.4	7.5
2-11 years; Inj. site Swelling, Post-Inj. 1	3.8	6.3
12-17 years; Injection site Pain, Post- Inj. 1	28.4	28.3
12-17 years; Inj. site Erythema, Post- Inj. 1	0.0	0.0
12-17 years; Inj. site Swelling, Post-Inj. 1	0.0	0.0
18-45 years; Injection site Pain, Post- Inj. 1	30.9	16.4
18-45 years; Inj. site Erythema, Post- Inj. 1	0.6	0.0

Population analysed: Analysis was performed on Safety analysis set. Here, 'number analyzed' = participants with available data for each specified category.

Primary outcome: Percentage of All Participants Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine or Placebo

Time frame: Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3. Number. Unit: Percentage of participants

Measure	CYD Dengue Vaccine Group n = 424	Placebo Group n = 140
CYD dengue Serotype 1; Pre-Injection 1	14.6	17.1
CYD dengue Serotype 1; Post-Injection 1	22.9	11.6
CYD dengue Serotype 1; Pre-Injection 2	30.1	16.7
CYD dengue Serotype 1; Post-Injection 2	54.9	18.3
CYD dengue Serotype 1; Pre-Injection 3	45.8	13.8
CYD dengue Serotype 1; Post-Injection 3	79.6	22.0
CYD dengue Serotype 2; Pre-Injection 1	16.1	15.0
CYD dengue Serotype 2; Post-Injection 1	39.5	10.1

Population analysed: Analysis was performed on Per-Protocol (PP) analysis set which included all participants who were vaccinated and had no protocol deviations. Here, 'number analyzed' = participants with available data for each specified category.

Primary outcome: Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo

Time frame: Pre-Injection 1 and 28 days Post-Injection 3. Number. Unit: Percentage of participants

Measure	CYD Dengue Vaccine Group n = 148	Placebo Group n = 47
2-11 years, CYD dengue Serotype 1; Pre-Inj. 1	4.7	8.5
2-11 years, CYD dengue Serotype 1; Post-Inj. 3	92.4	10.8
2-11 years, CYD dengue Serotype 2; Pre-Inj. 1	5.4	2.1
2-11 years, CYD dengue Serotype 2; Post-Inj. 3	93.9	16.2
2-11 years, CYD dengue Serotype 3; Pre-Inj. 1	11.6	10.6
2-11 years, CYD dengue Serotype 3; Post-Inj. 3	98.5	13.5
2-11 years, CYD dengue Serotype 4; Pre-Inj. 1	6.8	6.4
2-11 years, CYD dengue Serotype 4; Post-Inj. 3	96.9	18.9

Population analysed: Analysis was performed on Per-Protocol analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AE) were collected from Day 0 (post-vaccination) up to the end of 4th year of follow up (up to 60 months).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CYD Dengue Vaccine Group	43 of 898 (4.8%)	481 of 898 (53.6%)	3 of 898
Placebo Group	13 of 300 (4.3%)	198 of 300 (66%)	0 of 300

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Mar 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 23839107Harenberg A, Begue S, Mamessier A, Gimenez-Fourage S, Ching Seah C, Wei Liang A, Li Ng J, Yun Toh X, Archuleta S, Wilder-Smith A, Shek LP, Wartel-Tram A, Bouckenooghe A, Lang J, Crevat D, Caillet C, Guy B. Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore. Hum Vaccin Immunother. 2013 Nov;9(11):2317-25. doi: 10.4161/hv.25562. Epub 2013 Jul 9.
Derived from this study: PubMed 22894958Leo YS, Wilder-Smith A, Archuleta S, Shek LP, Chong CY, Leong HN, Low CY, Oh ML, Bouckenooghe A, Wartel TA, Crevat D. Immunogenicity and safety of recombinant tetravalent dengue vaccine (CYD-TDV) in individuals aged 2-45 y: Phase II randomized controlled trial in Singapore. Hum Vaccin Immunother. 2012 Sep;8(9):1259-71. doi: 10.4161/hv.21224. Epub 2012 Aug 16.
Related InfoLink provided by the sponsor.
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.

Medical Director study director

Sanofi Pasteur Inc.

5 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 5 inclusion and 16 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 5 sites in Singapore. 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 29 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?

Percentage of All Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Injection With CYD Dengue Vaccine or Placebo (time frame: Day 0 up to 14 days post-any and each injection). The study lists 7 primary outcomes in all. 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 NCT00880893, which also lists 2 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.