Dengue FeverPhase 2NCT02628444

Immunogenicity and Safety of Different Vaccination Schedules of Tetravalent Dengue Vaccine in Healthy Subjects 9 to 50 Years of Age

A Phase 2 study testing CYD Dengue Vaccine in people with Dengue Fever and Dengue Hemorrhagic Fever, run by Sanofi Pasteur, a Sanofi Company at 6 sites in 2 countries.

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

The aim of the study was to assess the immune response and the safety of different vaccination schedules of CYD dengue vaccine. The primary objectives of the study were: To demonstrate the non-inferiority of the immune response elicited against each dengue serotype by CYD dengue vaccine given as a 2-dose schedule… Read more about this study

Who is it for?: Ages 9 to 50 yearsHealthy volunteers can take part
Conditions the study is for: Dengue Fever, Dengue Hemorrhagic Fever
What is being tested?: CYD Dengue Vaccine
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 1,050 participants
Where: 6 sitesin 2 countries
Study dates: 2 May 2016to 29 Apr 2020
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 9 to 50 years
All sexes
Healthy volunteers accepted
Child, Adult

Who may be able to join

Aged 9 to 50 years on the day of enrollment.
Participant in good health, based on medical history and physical examination.
Assent form or informed consent form (ICF) had been signed and dated by the participant (based on local regulations), and ICF had been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations).
Participant and parent(s)/legally acceptable representative(s) were able to attend all scheduled visits and to comply with all trial procedures.

Who cannot join

Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche, 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 at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device or medical procedure.
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 corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
Self-reported systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances.
Chronic illness that, in the opinion of the investigator, was 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.

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Planned receipt of any vaccine in the 4 weeks following any trial vaccination.
Previous vaccination against dengue disease with either the trial vaccine or another vaccine.
Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
Current alcohol abuse or drug addiction that, based on investigator's judgment, might interfere with the participant's ability to comply with trial procedures.
Identified as a site employee of the Investigator, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife, and their children, adopted or natural) of the employees or the Investigator.
A prospective participant must not be included in the study until the following conditions and/or symptoms were resolved:
Febrile illness (temperature greater than or equal to [>=] 38.0 degree Celsius) or moderate or severe acute illness/infection (according to Investigator's judgment) on the day of vaccination.
Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.

Trial locations and contacts

6 sites in 2 countries.

Country

City, postcode or hospital

6 sites in 2 countries

Colombia3 sites

Investigational Site 102
Barranquilla
Investigational Site 101
Cali
Investigational Site 103
Medellín

Other trials in Colombia

Philippines3 sites

Investigational Primary Site Muntinlupa 201_Satellite Site San Pablo 202
City of Muntinlupa
Investigational Site 203
Manila
Investigational Site 204
Manila

Other trials in Philippines

About this study

Official title: Immunogenicity and Safety of Tetravalent Dengue Vaccine Given in 1-, 2-, or 3- Dose Schedules (STAGE I) Followed by a Single Booster Injection of the Same Vaccine (STAGE II) 1 or 2 Years After the Last Primary Dose in Healthy Subjects 9 to 50 Years of Age in Colombia and the Philippines

The aim of the study was to assess the immune response and the safety of different vaccination schedules of CYD dengue vaccine.

The primary objectives of the study were:

To demonstrate the non-inferiority of the immune response elicited against each dengue serotype by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants 28 days after the last injection.
To demonstrate the non-inferiority of the immune response elicited against each dengue serotype by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD vaccine given as a 3-dose schedule (Group 1) in previously dengue exposed participants, 1 year after the last injection.
To demonstrate the non-inferiority of the immune response elicited against each dengue serotype elicited by a booster dose of CYD dengue vaccine one year or two years after the last injection in the primary series in previously dengue exposed participants, compared to the immune response post dose 3 in Group 1.

The secondary objectives of the study were:

To demonstrate the superiority of the immune response elicited by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants, 28 days after the last injection.
To demonstrate the superiority of the immune response elicited by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants, one year after the last injection.
To describe the neutralizing antibody levels of each dengue serotype at 28 days post-injection 3 to the antibody levels immediately before receiving a booster dose, by baseline dengue serostatus.
To describe the neutralizing antibody levels of each dengue serotype at 28 days post-injection 2 and 28 days post-injection 3 from Group 1 in a primary series schedule by baseline dengue serostatus.
To demonstrate the superiority of the immune response elicited against each dengue serotype 28 days after administration of a booster dose of CYD dengue vaccine, in previously dengue exposed participants, at one year or two years after last injection in the primary series.
To describe the seroconversion rate 28 days post-booster injection in all 3 groups.
To describe all hospitalized virologically confirmed dengue (VCD) cases during the study.
To evaluate the safety profile of CYD after each and any injection during the trial. 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.

Read the detailed description

Healthy participants aged between 9 and 50 year received CYD dengue vaccine in various schedules, in two sequential stages. In the first stage, participants received 1, 2 or 3 injections of CYD dengue vaccine over a 12-month period. In the second stage, participants were randomized to receive a booster dose of CYD dengue vaccine at either 12 months (Subgroup a) or 24 months (Subgroup b) after the third injection of study vaccine. During the conduction of this trial, the World Health Organization (WHO) indication about vaccinating only baseline seropositive participants was arisen; at this moment, STAGE I of the trial was completed. For STAGE II, only participants who were previously dengue exposed at baseline (dengue seropositive) were eligible to receive the booster dose.

Conditions: Dengue Fever, Dengue Hemorrhagic Fever
Being tested: CYD Dengue Vaccine, Placebo (Sodium chloride 0.9%)
Keywords: Dengue Fever, Dengue virus, Dengue Hemorrhagic Fever, 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
0.5 mL, Subcutaneous
Placebo (Sodium chloride 0.9%)Biological
0.5 mL, Subcutaneous

Study groups in NCT02628444
Study group	Role	What they receive
STAGE-I Group 1: CYD Dengue Vaccine	Experimental	Participants received 3 doses of CYD dengue vaccine 0.5 milliliters (mL) subcutaneously (SC) at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Receives: Biological: CYD Dengue Vaccine
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	Experimental	Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Receives: Biological: CYD Dengue Vaccine; Biological: Placebo (Sodium chloride 0.9%)
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	Experimental	Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3). Receives: Biological: CYD Dengue Vaccine; Biological: Placebo (Sodium chloride 0.9%)
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	Experimental	Participants from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Receives: Biological: CYD Dengue Vaccine
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	Experimental	Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Receives: Biological: CYD Dengue Vaccine; Biological: Placebo (Sodium chloride 0.9%)
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	Experimental	Participants from Group 3 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Receives: Biological: CYD Dengue Vaccine; Biological: Placebo (Sodium chloride 0.9%)
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	Experimental	Participants from Group 1 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Receives: Biological: CYD Dengue Vaccine
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	Experimental	Participants from Group 2 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Receives: Biological: CYD Dengue Vaccine; Biological: Placebo (Sodium chloride 0.9%)
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	Experimental	Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Receives: Biological: CYD Dengue Vaccine; Biological: Placebo (Sodium chloride 0.9%)

What is being measured

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

STAGE-I: Geometric Mean Titers (GMTs) Against Each Dengue Virus Serotype 28 Days After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3, or 4) were assessed using plaque reduction neutralization test (PRNT) assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline was defined as participants with titers >=10 (1/dilution) for at least 1 serotype with parental dengue virus strains. Per-protocol analysis set (PPAS) included all participants who had no protocol violations; and who met any of following study violations were excluded from PPAS (STAGE I/II): had not met all protocol-specified inclusion/exclusion criteria, had not received correct doses or injections, received vaccine other than randomized schedule, did not receive vaccination in proper time window, had not provided post-dose serology sample in proper time window, received protocol-restricted medication, therapy, or vaccine.
Measured: 28 days after last CYD dengue vaccination
STAGE-I: Geometric Mean Titers Against Each Dengue Virus Serotype 1 Year After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains.
Measured: 1 year after last CYD dengue vaccination
STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 1a (28 days 12 months Booster dose) were reported and compared in this outcome measure. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1a: 28 days post 12 months booster dose in STAGE-II by Group 1: 28 days post-dose 3 in STAGE-I.
Measured: Group 1: 28 days post-dose 3 in STAGE-I, Group 1a: 28 days post 12 months booster dose in STAGE-II
STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2a (28 days post 12 months Booster dose) were reported and compared in this outcome measure. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2a: 28 days post 12 months booster dose in STAGE-II by Group 1: 28 days Post-dose 3 in STAGE-I.
Measured: Group 1: 28 days post-dose 3 in STAGE-I, Group 2a: 28 days post 12 months booster dose in STAGE-II
STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1b and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 1b (28 days post 24 months booster dose) were reported and compared in this outcome measure. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1b: 28 days post 24 months booster dose in STAGE-II by Group 1: 28 days Post-dose 3 in STAGE-I.
Measured: Group 1: 28 days post-dose 3 in STAGE-I, Group 1b: 28 days post 24 months booster dose in STAGE-II
STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2b and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2b (28 days post 24 months Booster dose) was reported and compared in this outcome measure. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2b: 28 days post 24 months booster dose in STAGE-II by Group 1: 28 days post-dose 3 in STAGE-I.
Measured: Group 1: 28 days post-dose 3 in STAGE-I, Group 2b: 28 days post 24 months Booster dose in STAGE-II

Secondary outcomes (18)

STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline-Comparison Between Group 1 and Group 2
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains.
Measured: 28 days and 1 year after last CYD dengue vaccination
STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains in All Participants
GMTs of antibodies against each of the 4 dengue virus serotypes (parental strains) were assessed using the PRNT assay method.
Measured: Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains (by Baseline Dengue Status) in Participants Who Were Seropositive and Seronegative at Baseline
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3, or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Dengue seronegative participants at Baseline were defined as the participants with valid titer <0 (1/dilution) for all serotypes with parental dengue virus strains.
Measured: Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
STAGE-II: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After Booster CYD Dengue Vaccination in Participants Seropositive at Baseline
GMTs of antibodies against each of the 4 dengue virus serotype (1, 2, 3, or 4) were assessed using the PRNT assay. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Titers were measured in terms of 1/dilution.
Measured: Baseline, 28 days post vaccination-3, and 28 days post booster dose
STAGE-I: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strains in All Participants
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay.
Measured: Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
STAGE-II: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strain in Participants Seropositive at Baseline
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains.
Measured: Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
STAGE-I: Number of Participants With Immediate Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the electronic case report form (eCRF) in terms of diagnosis and/or onset post-vaccination. Immediate unsolicited AE were AEs that occurred within 30 minutes after any vaccination.
Measured: Within 30 minutes after any vaccination (1, 2, or 3)
STAGE-II: Number of Participants With Immediate Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the eCRF in terms of diagnosis and / or onset post-vaccination. Immediate unsolicited AE were AEs that occurred within 30 minutes after vaccination.
Measured: Within 30 minutes after CYD booster vaccination
STAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
Adverse reaction (AR) was defined as all noxious and unintended responses to a medicinal product related to any dose. A Solicited Reaction (SR) was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling.
Measured: Within 7 days after any vaccination (1, 2, or 3)
STAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)
AR was defined as all noxious and unintended responses to a medicinal product related to any dose. An SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling.
Measured: Within 7 days after each vaccination (1, 2, and 3)
STAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. An SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Systemic AEs were all AEs that were not injection site reactions. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia.
Measured: Within 14 days after any vaccination (1, 2, or 3)
STAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)
An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia.
Measured: Within 14 days after each vaccination (1, 2, and 3)
STAGE-II: Number of Participants With Solicited Injection Site Reactions Following Booster Vaccination With CYD Dengue Vaccine
An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling.
Measured: Within 7 days after CYD booster vaccination
STAGE-II: Number of Participants With Solicited Systemic Reactions Following Booster Vaccination With CYD Dengue Vaccine
An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia.
Measured: Within 14 days after CYD booster vaccination
STAGE-I: Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the eCRF in terms of diagnosis and/or onset post-vaccination.
Measured: Within 28 days after any vaccination (1, 2, or 3)
STAGE-II: Number of Participants Reporting Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of diagnosis and/or onset post-vaccination.
Measured: Within 28 days after CYD booster Vaccination
STAGE-I: Number of Participants Reporting Serious Adverse Events Including Serious Adverse Event of Special Interests (AESI) Following Vaccination With CYD Dengue Vaccine or Placebo
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, or was an important medical event. AESI were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine.
Measured: From Day 0 (post vaccination) up to 12 months after last vaccination in STAGE-I (i.e., up to 24 months)
STAGE-II: Number of Participants Reporting Serious Adverse Events Including Serious Adverse Events Special Interest Following Booster Vaccination With CYD Dengue Vaccine
An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, or was an important medical event. AESI were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine.
Measured: From Month 25 up to 6 months after CYD booster injection (either at 1 year or 2 year) (i.e., up to 30 months for Groups 1a, 2a, and 3a and up to 42 months for Groups 1b, 2b, and 3b)

Timeline

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

2 May 201629 Apr 2020

First posted11 Dec 2015 (estimated)
Study start2 May 2016
Primary completion29 Apr 2020
Study completion29 Apr 2020

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: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 1,050 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02628444
Sponsor's protocol ID: CYD65
Other IDs: U1111-1161-3242, 2020-002854-25
Status last verified: Mar 2022
First submitted: 9 Dec 2015
Last updated: 24 Mar 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
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

Coronel-Martinez DL, Park J, Lopez-Medina E, Capeding MR, Bonfanti AAC, Montalban MC, Ramirez I, Gonzales MLA, Zambrano B, Dayan G, Chen Z, Wang H, Bonaparte M, Rojas A, Ramirez JC, Verdan MA, Noriega F. Immunogenicity and safety of booster CYD-TDV dengue vaccine after alternative primary vaccination schedules in healthy individuals aged 9-50 years: a randomised, controlled, phase 2, non-inferiority study. Lancet Infect Dis. 2022 Jun;22(6):901-911. doi: 10.1016/S1473-3099(21)00706-4. Epub 2022 Mar 29.
PubMed 35364022
Coronel-MartInez DL, Park J, Lopez-Medina E, Capeding MR, Cadena Bonfanti AA, Montalban MC, Ramirez I, Gonzales MLA, DiazGranados CA, Zambrano B, Dayan G, Savarino S, Chen Z, Wang H, Sun S, Bonaparte M, Rojas A, Ramirez JC, Verdan MA, Noriega F. Immunogenicity and safety of simplified vaccination schedules for the CYD-TDV dengue vaccine in healthy individuals aged 9-50 years (CYD65): a randomised, controlled, phase 2, non-inferiority study. Lancet Infect Dis. 2021 Apr;21(4):517-528. doi: 10.1016/S1473-3099(20)30767-2. Epub 2020 Nov 16.
PubMed 33212067

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?
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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 24 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Immunogenicity and Safety of Tetravalent Dengue Vaccine Given in 1-, 2-, or 3- Dose Schedules (STAGE I) Followed by a Single Booster Injection of the Same Vaccine (STAGE II) 1 or 2 Years After the Last Primary Dose in Healthy Subjects 9 to 50 Years of Age in Colombia and the Philippines
ClinicalTrials.gov ID: NCT02628444
Acronym / sponsor ID: CYD65
Conditions: Dengue Fever, Dengue Hemorrhagic Fever
Keywords: Dengue Fever, Dengue virus, Dengue Hemorrhagic Fever, CYD Dengue Vaccine
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 1,050 participants (actual)
Lead sponsor: Sanofi Pasteur, a Sanofi CompanyIndustry (pharma, biotech, devices)
Study start: 2 May 2016 (actual)
Primary completion: 29 Apr 2020 (actual)
Study completion: 29 Apr 2020 (actual)
First posted: 11 Dec 2015 (estimated)
Results: Posted 23 Feb 2021

Clinical summary

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

The aim of the study was to assess the immune response and the safety of different vaccination schedules of CYD dengue vaccine.

The primary objectives of the study were:

To demonstrate the non-inferiority of the immune response elicited against each dengue serotype by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants 28 days after the last injection.
To demonstrate the non-inferiority of the immune response elicited against each dengue serotype by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD vaccine given as a 3-dose schedule (Group 1) in previously dengue exposed participants, 1 year after the last injection.
To demonstrate the non-inferiority of the immune response elicited against each dengue serotype elicited by a booster dose of CYD dengue vaccine one year or two years after the last injection in the primary series in previously dengue exposed participants, compared to the immune response post dose 3 in Group 1.

The secondary objectives of the study were:

To demonstrate the superiority of the immune response elicited by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants, 28 days after the last injection.
To demonstrate the superiority of the immune response elicited by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants, one year after the last injection.
To describe the neutralizing antibody levels of each dengue serotype at 28 days post-injection 3 to the antibody levels immediately before receiving a booster dose, by baseline dengue serostatus.
To describe the neutralizing antibody levels of each dengue serotype at 28 days post-injection 2 and 28 days post-injection 3 from Group 1 in a primary series schedule by baseline dengue serostatus.
To demonstrate the superiority of the immune response elicited against each dengue serotype 28 days after administration of a booster dose of CYD dengue vaccine, in previously dengue exposed participants, at one year or two years after last injection in the primary series.
To describe the seroconversion rate 28 days post-booster injection in all 3 groups.
To describe all hospitalized virologically confirmed dengue (VCD) cases during the study.
To evaluate the safety profile of CYD after each and any injection during the trial. 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.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 9

Arm	Type	Receives
STAGE-I Group 1: CYD Dengue Vaccine	Experimental	Biological: CYD Dengue VaccineParticipants received 3 doses of CYD dengue vaccine 0.5 milliliters (mL) subcutaneously (SC) at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3).
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	Experimental	Biological: CYD Dengue Vaccine, Biological: Placebo (Sodium chloride 0.9%)Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3).
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	Experimental	Biological: CYD Dengue Vaccine, Biological: Placebo (Sodium chloride 0.9%)Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	Experimental	Biological: CYD Dengue VaccineParticipants from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	Experimental	Biological: CYD Dengue Vaccine, Biological: Placebo (Sodium chloride 0.9%)Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	Experimental	Biological: CYD Dengue Vaccine, Biological: Placebo (Sodium chloride 0.9%)Participants from Group 3 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	Experimental	Biological: CYD Dengue VaccineParticipants from Group 1 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	Experimental	Biological: CYD Dengue Vaccine, Biological: Placebo (Sodium chloride 0.9%)Participants from Group 2 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	Experimental	Biological: CYD Dengue Vaccine, Biological: Placebo (Sodium chloride 0.9%)Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).

Who may qualify

Ages: 9 to 50 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (4 listed)

Aged 9 to 50 years on the day of enrollment.
Participant in good health, based on medical history and physical examination.
Assent form or informed consent form (ICF) had been signed and dated by the participant (based on local regulations), and ICF had been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations).
Participant and parent(s)/legally acceptable representative(s) were able to attend all scheduled visits and to comply with all trial procedures.

Key exclusion criteria (14 listed)

Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche, 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 at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device or medical procedure.
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 corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
Self-reported systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances.
Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with trial conduct or completion.

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 Vaccine0.5 mL, Subcutaneous	Biological	STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12), STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12), STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year), STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years), STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year), STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years), STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year), STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Placebo (Sodium chloride 0.9%)0.5 mL, Subcutaneous	Biological	STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12), STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12), STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year), STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years), STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year), STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)

Primary outcome

STAGE-I: Geometric Mean Titers (GMTs) Against Each Dengue Virus Serotype 28 Days After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Time frame: 28 days after last CYD dengue vaccination
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3, or 4) were assessed using plaque reduction neutralization test (PRNT) assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline was defined as participants with titers >=10 (1/dilution) for at least 1 serotype with parental dengue virus strains. Per-protocol analysis set (PPAS) included all participants who had no protocol violations; and who met any of following study violations were excluded from PPAS (STAGE I/II): had not met all protocol-specified inclusion/exclusion criteria, had not received correct doses or injections, received vaccine other than randomized schedule, did not receive vaccination in proper time window, had not provided post-dose serology sample in proper time window, received protocol-restricted medication, therapy, or vaccine.
STAGE-I: Geometric Mean Titers Against Each Dengue Virus Serotype 1 Year After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Time frame: 1 year after last CYD dengue vaccination
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains.
STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Time frame: Group 1: 28 days post-dose 3 in STAGE-I, Group 1a: 28 days post 12 months booster dose in STAGE-II
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 1a (28 days 12 months Booster dose) were reported and compared in this outcome measure. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1a: 28 days post 12 months booster dose in STAGE-II by Group 1: 28 days post-dose 3 in STAGE-I.
STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Time frame: Group 1: 28 days post-dose 3 in STAGE-I, Group 2a: 28 days post 12 months booster dose in STAGE-II
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2a (28 days post 12 months Booster dose) were reported and compared in this outcome measure. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2a: 28 days post 12 months booster dose in STAGE-II by Group 1: 28 days Post-dose 3 in STAGE-I.
STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1b and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Time frame: Group 1: 28 days post-dose 3 in STAGE-I, Group 1b: 28 days post 24 months booster dose in STAGE-II
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 1b (28 days post 24 months booster dose) were reported and compared in this outcome measure. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1b: 28 days post 24 months booster dose in STAGE-II by Group 1: 28 days Post-dose 3 in STAGE-I.
STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2b and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Time frame: Group 1: 28 days post-dose 3 in STAGE-I, Group 2b: 28 days post 24 months Booster dose in STAGE-II
GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2b (28 days post 24 months Booster dose) was reported and compared in this outcome measure. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2b: 28 days post 24 months booster dose in STAGE-II by Group 1: 28 days post-dose 3 in STAGE-I.

18 secondary outcomes

STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline-Comparison Between Group 1 and Group 2
Time frame: 28 days and 1 year after last CYD dengue vaccination
STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains in All Participants
Time frame: Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains (by Baseline Dengue Status) in Participants Who Were Seropositive and Seronegative at Baseline
Time frame: Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
STAGE-II: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After Booster CYD Dengue Vaccination in Participants Seropositive at Baseline
Time frame: Baseline, 28 days post vaccination-3, and 28 days post booster dose
STAGE-I: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strains in All Participants
Time frame: Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
STAGE-II: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strain in Participants Seropositive at Baseline
Time frame: Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
STAGE-I: Number of Participants With Immediate Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
Time frame: Within 30 minutes after any vaccination (1, 2, or 3)
STAGE-II: Number of Participants With Immediate Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine
Time frame: Within 30 minutes after CYD booster vaccination
STAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
Time frame: Within 7 days after any vaccination (1, 2, or 3)
STAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)
Time frame: Within 7 days after each vaccination (1, 2, and 3)
STAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
Time frame: Within 14 days after any vaccination (1, 2, or 3)
STAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)
Time frame: Within 14 days after each vaccination (1, 2, and 3)
STAGE-II: Number of Participants With Solicited Injection Site Reactions Following Booster Vaccination With CYD Dengue Vaccine
Time frame: Within 7 days after CYD booster vaccination
STAGE-II: Number of Participants With Solicited Systemic Reactions Following Booster Vaccination With CYD Dengue Vaccine
Time frame: Within 14 days after CYD booster vaccination
STAGE-I: Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo
Time frame: Within 28 days after any vaccination (1, 2, or 3)
STAGE-II: Number of Participants Reporting Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine
Time frame: Within 28 days after CYD booster Vaccination
STAGE-I: Number of Participants Reporting Serious Adverse Events Including Serious Adverse Event of Special Interests (AESI) Following Vaccination With CYD Dengue Vaccine or Placebo
Time frame: From Day 0 (post vaccination) up to 12 months after last vaccination in STAGE-I (i.e., up to 24 months)
STAGE-II: Number of Participants Reporting Serious Adverse Events Including Serious Adverse Events Special Interest Following Booster Vaccination With CYD Dengue Vaccine
Time frame: From Month 25 up to 6 months after CYD booster injection (either at 1 year or 2 year) (i.e., up to 30 months for Groups 1a, 2a, and 3a and up to 42 months for Groups 1b, 2b, and 3b)

Results and safety

Results posted to the registry on 23 Feb 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
STAGE-I Group 1: CYD Dengue Vaccine	350	314
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	348	309
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	352	310
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	0	0
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	0	0
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	0	0
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	0	0
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	0	0
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	0	0

Primary outcome: STAGE-I: Geometric Mean Titers (GMTs) Against Each Dengue Virus Serotype 28 Days After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline

Time frame: 28 days after last CYD dengue vaccination. Geometric mean (95% Confidence Interval). Unit: titers

Measure	STAGE-I Group 1: CYD Dengue Vaccine n = 265	STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) n = 272
Serotype 1	822 (700 to 964)	899 (752 to 1075)
Serotype 2	875 (770 to 995)	869 (754 to 1002)
Serotype 3	610 (535 to 694)	599 (524 to 685)
Serotype 4	531 (470 to 601)	510 (453 to 575)

STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12): GMT Ratio: 1.09 (95% CI 0.862 to 1.39)
STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12): GMT Ratio: 0.993 (95% CI 0.820 to 1.20)
STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12): GMT Ratio: 0.983 (95% CI 0.816 to 1.18)

Population analysed: Analysis performed on PPAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Group 3, as pre-specified in protocol.

Primary outcome: STAGE-I: Geometric Mean Titers Against Each Dengue Virus Serotype 1 Year After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline

Time frame: 1 year after last CYD dengue vaccination. Geometric mean (95% Confidence Interval). Unit: titers

Measure	STAGE-I Group 1: CYD Dengue Vaccine n = 185	STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) n = 190
Serotype 1	490 (398 to 604)	504 (403 to 630)
Serotype 2	821 (704 to 957)	737 (611 to 888)
Serotype 3	477 (405 to 561)	437 (368 to 519)
Serotype 4	270 (235 to 310)	238 (205 to 277)

STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12): GMT Ratio: 1.03 (95% CI 0.757 to 1.40)
STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12): GMT Ratio: 0.897 (95% CI 0.705 to 1.14)
STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12): GMT Ratio: 0.917 (95% CI 0.724 to 1.16)

Population analysed: Analysis was performed on PPAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Group 3, as pre-specified in protocol.

Primary outcome: STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline

Time frame: Group 1: 28 days post-dose 3 in STAGE-I, Group 1a: 28 days post 12 months booster dose in STAGE-II. Geometric mean (98.75% Confidence Interval). Unit: titers

Measure	Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I n = 53	Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose n = 53
Serotype 1	853 (526 to 1384)	483 (281 to 832)
Serotype 2	1186 (809 to 1738)	884 (602 to 1300)
Serotype 3	696 (483 to 1002)	722 (458 to 1140)
Serotype 4	592 (400 to 876)	383 (269 to 545)

Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose: GMT paired ratio: 0.567 (98.75% CI 0.399 to 0.805)
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose: GMT paired ratio: 0.746 (98.75% CI 0.550 to 1.01)
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose: GMT paired ratio: 1.04 (98.75% CI 0.686 to 1.57)

Population analysed: Analysis was performed on PPAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure.

Primary outcome: STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline

Time frame: Group 1: 28 days post-dose 3 in STAGE-I, Group 2a: 28 days post 12 months booster dose in STAGE-II. Geometric mean (98.75% Confidence Interval). Unit: titers

Measure	Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I n = 112	Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose n = 58
Serotype 1	875 (614 to 1248)	549 (331 to 911)
Serotype 2	1023 (771 to 1356)	828 (569 to 1203)
Serotype 3	568 (433 to 745)	676 (436 to 1049)
Serotype 4	540 (418 to 697)	270 (200 to 364)

Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose: GMT Ratio: 0.627 (98.75% CI 0.342 to 1.15)
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose: GMT Ratio: 0.809 (98.75% CI 0.505 to 1.30)
Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose: GMT Ratio: 1.19 (98.75% CI 0.732 to 1.94)

Population analysed: Analysis was performed on PPAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure.

18 secondary outcomes are reported in the full results.

Adverse events

Time frame: Unsolicited non-serious AEs: Day 0 to Day 28 post any vaccination SR: within 7 & 14 days post any vaccination; SAE: up to 24 months for STAGE-I); up to 6 months after last vaccination for Stage-2 (i.e., up to 30 months [for Groups 1a, 2a, and 3a]; & up to 42 months [for Groups 1b, 2b, and 3b]). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
STAGE-I Group 1: CYD Dengue Vaccine	14 of 348 (4%)	203 of 348 (58.3%)	0 of 348
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)	26 of 348 (7.5%)	189 of 348 (54.3%)	1 of 348
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)	18 of 352 (5.1%)	182 of 352 (51.7%)	1 of 352
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)	3 of 55 (5.5%)	10 of 55 (18.2%)	0 of 55
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)	2 of 53 (3.8%)	13 of 53 (24.5%)	0 of 53
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)	0 of 59 (0%)	15 of 59 (25.4%)	0 of 59
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)	0 of 56 (0%)	20 of 56 (35.7%)	0 of 56
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)	2 of 62 (3.2%)	18 of 62 (29%)	0 of 62
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)	1 of 53 (1.9%)	15 of 53 (28.3%)	0 of 53

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 35364022Coronel-Martinez DL, Park J, Lopez-Medina E, Capeding MR, Bonfanti AAC, Montalban MC, Ramirez I, Gonzales MLA, Zambrano B, Dayan G, Chen Z, Wang H, Bonaparte M, Rojas A, Ramirez JC, Verdan MA, Noriega F. Immunogenicity and safety of booster CYD-TDV dengue vaccine after alternative primary vaccination schedules in healthy individuals aged 9-50 years: a randomised, controlled, phase 2, non-inferiority study. Lancet Infect Dis. 2022 Jun;22(6):901-911. doi: 10.1016/S1473-3099(21)00706-4. Epub 2022 Mar 29.
Derived from this study: PubMed 33212067Coronel-MartInez DL, Park J, Lopez-Medina E, Capeding MR, Cadena Bonfanti AA, Montalban MC, Ramirez I, Gonzales MLA, DiazGranados CA, Zambrano B, Dayan G, Savarino S, Chen Z, Wang H, Sun S, Bonaparte M, Rojas A, Ramirez JC, Verdan MA, Noriega F. Immunogenicity and safety of simplified vaccination schedules for the CYD-TDV dengue vaccine in healthy individuals aged 9-50 years (CYD65): a randomised, controlled, phase 2, non-inferiority study. Lancet Infect Dis. 2021 Apr;21(4):517-528. doi: 10.1016/S1473-3099(20)30767-2. Epub 2020 Nov 16.
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

6 sites in 2 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing CYD Dengue Vaccine in people with Dengue Fever and Dengue Hemorrhagic Fever, run by Sanofi Pasteur, a Sanofi Company at 6 sites in 2 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 14 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 24 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 6 sites in Colombia, Philippines. 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. 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 23 Feb 2021). 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?

STAGE-I: Geometric Mean Titers (GMTs) Against Each Dengue Virus Serotype 28 Days After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline (time frame: 28 days after last CYD dengue vaccination). The study lists 6 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 NCT02628444, 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 24 Mar 2022.