Dengue FeverPhase 3NCT02992418

Study of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Adacel® in Healthy Subjects

A Phase 3 study testing CYD Dengue Vaccine and Tdap: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine adsorbed in people with Dengue Fever and Dengue Hemorrhagic Fever, run by Sanofi Pasteur, a Sanofi Company at 4 sites in Philippines.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

The aim of the study was to investigate the immunogenicity and safety of CYD dengue vaccine and Tetanus Toxoid (T), Reduced Diphtheria Toxoid (D) and Acellular Pertussis Vaccine Adsorbed (ap) (Tdap) vaccine when both vaccines were administered concomitantly or sequentially. Read more about this study

Who is it for?: Ages 9 to 60 yearsHealthy volunteers can take part
Conditions the study is for: Dengue Fever, Dengue Hemorrhagic Fever
What is being tested?: CYD Dengue Vaccine and Tdap: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine adsorbed
Type of treatment: Vaccines, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 688 participants
Where: 4 sitesPhilippines
Study dates: 19 Dec 2016to 10 Dec 2019
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

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

Ages 9 to 60 years
All sexes
Healthy volunteers accepted
Child, Adult

Who may be able to join

Participant aged 9 to 60 years (i.e., from the day of the 9th birthday to the day prior to the 61th birthday) on the day of inclusion.
Participant in good health, based on medical history and physical examination.
Informed consent form (ICF) or assent form was signed and dated by the participant (based on local regulations), and/or ICF was signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations).
For participant aged 9 to 11 years: known (documented) receipt of at least 4 previous doses of diphtheria toxoid, tetanus toxoid and acellular pertussis-containing (DTaP) vaccines, with the last dose not within the last 5 years prior to enrolment.
OR For participant aged at least 12 years: known (documented or self-reported) receipt of at least 3 previous doses of diphtheria toxoid, tetanus toxoid, and whole cell pertussis-containing (DTwP) vaccines, with the last dose not within the last 5 years prior to enrolment.
Participant (or participant and parent[s]/legally acceptable representatives) was able to attend all scheduled visits and complied 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 or post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination).
Participation 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.
Planned receipt of any vaccine in the 4 weeks following any trial vaccination.
Previous vaccination against dengue disease with the trial CYD dengue vaccine.
Receipt of immune globulins, blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response.
Known or suspected congenital or acquired immunodeficiency (including human immunodeficiency virus (HIV) infection with impaired immune function); or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroids therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).

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A previous severe reaction to pertussis, diphtheria or tetanus vaccine including immediate anaphylaxis, encephalopathy within 7 days or seizure within 3 days of receiving the vaccine.
Known 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.
Thrombocytopenia, contraindicating IM vaccination.
Bleeding disorder or receipt of anticoagulants within 3 weeks preceding inclusion, which might be a contraindication for IM vaccination, at the discretion of the Investigator.
Deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized involuntarily.
Current alcohol abuse or drug addiction that, based on Investigator's judgment, may interfere with the participant's ability to comply with trial procedures.
Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with trial conduct or completion.
Identified as an Investigator or employee of the Investigator with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.
Self-reported HIV, Hepatitis B, or Hepatitis C infection.
Personal history of Guillain-Barré syndrome.

Trial locations and contacts

4 sites in 1 country.

Philippines4 sites

Study site
City of Muntinlupa, Alabang
Study site
Manila, 1000
Study site
Quezon
Study site
Quezon City

Other trials in Philippines

About this study

Official title: Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Adacel® in Healthy Subjects Aged 9 to 60 Years in the Philippines

Primary Objectives:

To demonstrate the non-inferiority of the humoral immune response to the Tdap booster dose concomitantly administered with the first dose of CYD dengue vaccine as compared to sequential administration, measured 28 days after Tdap booster dose.
To demonstrate the non-inferiority of the humoral immune response to the first dose of CYD dengue vaccine concomitantly administered with Tdap as compared to sequential administration, measured 28 days after the first dose of CYD dengue vaccine.

Secondary Objectives:

To demonstrate the non-inferiority of the humoral immune response of 3 doses of CYD dengue vaccine with the first dose concomitantly administered with Tdap as compared to sequential administration, measured 28 days after the third dose of CYD dengue vaccine.
To describe the humoral immune response at baseline and 28 days after the first and third doses of CYD dengue vaccine, in each and any group.
To describe the humoral immune response of Tdap vaccine at baseline and 28 days after concomitant administration with the first dose of CYD dengue vaccine as compared to the sequential administration, in each and any group.
To describe the safety of the CYD dengue vaccine and of the Tdap booster dose after each and any injection in each group.

Read the detailed description

Participants were to receive CYD dengue vaccine according to a 3-dose schedule administered 6 months apart, with the first dose of CYD dengue vaccine administered either concomitantly or sequentially with a booster dose of the Tdap vaccine, Adacel®.

During the conduct of the study, a safety signal was identified which led to the Independent Data Monitoring Committee (IDMC) recommendation not to vaccinate participants who had never been infected by dengue prior to the first injection, i.e., dengue non-immune participants. The protocol was amended accordingly but never implemented due to absence of response of Health Authorities (HA) from The Philippines.

After having waited for more than 1.5 years, and as the participants became out of window to complete their immunization schedule and the last safety follow-up call (6 months after the last dose), the Sponsor decided to stop the trial. Participants only attended a last safety follow-up visit to terminate the study and were informed about the end of the study. As a consequence, the study was prematurely terminated before injection of the last dose (3rd dose) of the CYD dengue vaccine.

As a consequence of the IDMC recommendations, the main immunogenicity analyses were done in dengue immune participants which is not what was planned in the protocol (and this is why the primary endpoints are not exactly the same as those defined in the protocol as they were finally assessed only in dengue immune participants whereas initially it was planned to be assessed regardless of baseline status).

All participants were assessed for immunogenicity and safety. Safety assessments included 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.

Conditions: Dengue Fever, Dengue Hemorrhagic Fever
Being tested: CYD Dengue Vaccine, Tdap: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine adsorbed
Keywords: Dengue Fever, Dengue Hemorrhagic Fever, CYD Dengue Vaccine, Dengavaxia®
Medical subject headings: Dengue, Severe Dengue

What participants receive

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

CYD Dengue VaccineBiological
Also called Dengvaxia®
0.5 milliliter (mL), Subcutaneous at Month 1, 7 and Month 13, respectively
Tdap: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine adsorbedBiological
Also called Adacel®
0.5 mL, intramuscularly (IM) at Month 1.
Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbedBiological
Also called Adacel®
0.5 mL, intramuscularly at Day 0.

Study groups in NCT02992418
Study group	Role	What they receive
Concomitant Administration Group	Experimental	Participants will be administered the first dose of CYD dengue vaccine concomitantly with a dose of Tdap vaccine. Receives: Biological: CYD Dengue Vaccine; Biological: Tdap: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine adsorbed
Sequential Administration Group	Experimental	Participants will be administered the first dose of CYD dengue vaccine 28 days after a dose of Tdap vaccine. Receives: Biological: CYD Dengue Vaccine; Biological: Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed

What is being measured

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

Geometric Mean Concentrations (GMCs) of Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) 28 Days After Dose of Tdap Vaccine in Previously Dengue Immune Participants
GMCs against each pertussis antigens (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], fimbriae types 2 and 3 [FIM2+3]) were assessed using an enzyme-linked immunosorbent assay (ELISA) method and were measured in ELISA unit/milliliter (EU/mL). Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Measured: 28 days after Tdap vaccination
Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants
Seroprotection against diphtheria (Anti-D) and tetanus (Anti-T) antigens was performed by Micrometabolic Inhibition Test - Toxin Neutralization assay (MIT-TNA) and ELISA, respectively. Seroprotection was defined as anti-D and anti-T Ab concentration greater than 0.1 international units (IU)/mL. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Measured: 28 days after Tdap vaccination
Geometric Mean Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using the 50% plaque reduction neutralization test (PRNT50) assay method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Titers were measured in terms of 1/dilution.
Measured: 28 days after first CYD dengue vaccination

Secondary outcomes (12)

Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using PRNT50 assay method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Titers were measured in terms of 1/dilution.
Measured: Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination
Percentage of Participants With Neutralizing Antibody Titers Against Each of the 4 Dengue Virus Serotypes of CYD at Baseline and 28 Days After First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using PRNT50 assay method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Measured: Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination
Percentage of Participants With Neutralizing Antibody Titers Above Predefined Thresholds Against at Least 1, 2, 3, or 4 Serotypes of CYD at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (1, 2, 3, and 4) were measured by PRNT50. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Percentage of participants with neutralizing antibody titers above pre-defined thresholds (>=10 and >=100 [1/dilution]) against at least 1, 2, 3, or 4 serotypes of CYD were reported. Here, 'dil'=dilution and "vac"=vaccination in the specified categories.
Measured: Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination
Geometric Mean Concentrations of Serum Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) at Baseline and 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants
GMCs against each pertussis antigens (PT, FHA, PRN, FIM2+3) were assessed using ELISA assay method and were measured in EU/mL. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Measured: Baseline (Pre-Tdap vaccination) and 28 days after the Tdap vaccination
Percentage of Participants Achieving Serum Antibody (>=0.1 IU/mL) Against Diphtheria and Tetanus Antigens at Baseline and 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants
The GMC against diphtheria and tetanus antigens was performed by MIT-TNA and ELISA, respectively. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Measured: Baseline (Pre-Tdap vaccination) and 28 days after the dose of Tdap vaccination
Number of Participants With Immediate Unsolicited Adverse Events (AE) Following Vaccination With Tdap or CYD Dengue Vaccine
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. Any unsolicited AE occurred during first 30 minutes post-vaccination was recorded on the CRF as immediate AE. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccination and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received CYD vaccination.
Measured: Within 30 minutes after any and each vaccination
Number of Participants With Solicited Injection Site Reactions Following Vaccination With Tdap or CYD Dengue Vaccine
A solicited reaction (SR) was an AE 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 reactions included pain, erythema, and swelling. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received only CYD vaccination.
Measured: Within 7 days after any and each vaccination
Number of Participants With Solicited Systemic Reactions Following Vaccination With Tdap or CYD Dengue Vaccine
A SR reaction was an AE observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRF and considered as related to vaccination. Solicited injection site reactions included fever, headache, malaise, myalgia, and asthenia. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received only CYD vaccination.
Measured: Within 14 days after any and each vaccination
Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With Tdap or CYD Dengue Vaccine
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. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received CYD vaccination.
Measured: Within 28 days after any and each vaccination
Number of Participants Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Tdap or CYD Dengue Vaccine
Non-serious AESIs were non-serious AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received CYD vaccination.
Measured: Within 7 days post any and each vaccination
Number of Participants Reporting Serious Adverse Events (SAEs) and Serious AESIs Following Vaccination With Tdap or CYD Dengue Vaccine
SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; required hospitalization or prolonged existing hospitalization; persistent or significant disability/incapacity; congenital anomaly or a medically important event. Serious AESIs were SAEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine.
Measured: From Day 0 up to 6 months after the last Tdap or CYD vaccination
Number of Participants Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Tdap or CYD Dengue Vaccine
Hospitalized suspected dengue case was defined as an acute febrile illness with diagnosis of dengue requiring hospitalization (with bed attribution). In such cases, 1 unplanned acute blood sample (within the first 5 days after fever onset) was collected for virological confirmation of hospitalized suspected dengue case. A suspected case was considered VCD if there was a detection of wild type dengue virus by dengue non-structural protein 1 antigen ELISA and/or dengue reverse transcriptase-polymerase chain reactions.
Measured: From Day 0 up to 6 months after the last Tdap or CYD vaccination

Timeline

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

19 Dec 201610 Dec 2019

First posted14 Dec 2016 (estimated)
Study start19 Dec 2016
Primary completion10 Dec 2019
Study completion10 Dec 2019

Why it stopped: No answer received from the Philippines Food and Drug Administration on protocol amendment issued due to IDMC recommendations. CYD vaccine 3rd dose not given.

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 (1)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 3
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 688 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02992418
Sponsor's protocol ID: CYD66
Other IDs: U1111-1161-3294, 2019-003136-23, 2019
Status last verified: Mar 2022
First submitted: 12 Dec 2016
Last updated: 25 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

Santos J, Montellano ME, Solante R, Perreras N, Meyer S, Toh ML, Zocchetti C, Vigne C, Mascarenas C. Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Tdap Vaccine: Randomized Phase IIIb Trial in Healthy Participants 9-60 Years of Age in the Philippines. Pediatr Infect Dis J. 2021 Sep 1;40(9):856-863. doi: 10.1097/INF.0000000000003220.
PubMed 34117198

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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All Dengue Fever trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Adacel® in Healthy Subjects Aged 9 to 60 Years in the Philippines
ClinicalTrials.gov ID: NCT02992418
Acronym / sponsor ID: CYD66
Conditions: Dengue Fever, Dengue Hemorrhagic Fever
Keywords: Dengue Fever, Dengue Hemorrhagic Fever, CYD Dengue Vaccine, Dengavaxia®
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: No answer received from the Philippines Food and Drug Administration on protocol amendment issued due to IDMC recommendations. CYD vaccine 3rd dose not given.
Enrolment: 688 participants (actual)
Lead sponsor: Sanofi Pasteur, a Sanofi CompanyIndustry (pharma, biotech, devices)
Study start: 19 Dec 2016 (actual)
Primary completion: 10 Dec 2019 (actual)
Study completion: 10 Dec 2019 (actual)
First posted: 14 Dec 2016 (estimated)
Results: Posted 27 Aug 2020

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 demonstrate the non-inferiority of the humoral immune response to the Tdap booster dose concomitantly administered with the first dose of CYD dengue vaccine as compared to sequential administration, measured 28 days after Tdap booster dose.
To demonstrate the non-inferiority of the humoral immune response to the first dose of CYD dengue vaccine concomitantly administered with Tdap as compared to sequential administration, measured 28 days after the first dose of CYD dengue vaccine.

Secondary Objectives:

To demonstrate the non-inferiority of the humoral immune response of 3 doses of CYD dengue vaccine with the first dose concomitantly administered with Tdap as compared to sequential administration, measured 28 days after the third dose of CYD dengue vaccine.
To describe the humoral immune response at baseline and 28 days after the first and third doses of CYD dengue vaccine, in each and any group.
To describe the humoral immune response of Tdap vaccine at baseline and 28 days after concomitant administration with the first dose of CYD dengue vaccine as compared to the sequential administration, in each and any group.
To describe the safety of the CYD dengue vaccine and of the Tdap booster dose after each and any injection in each group.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Concomitant Administration Group	Experimental	Biological: CYD Dengue Vaccine, Biological: Tdap: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine adsorbedParticipants will be administered the first dose of CYD dengue vaccine concomitantly with a dose of Tdap vaccine.
Sequential Administration Group	Experimental	Biological: CYD Dengue Vaccine, Biological: Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbedParticipants will be administered the first dose of CYD dengue vaccine 28 days after a dose of Tdap vaccine.

Who may qualify

Ages: 9 to 60 years
Sex: All
Healthy volunteers: Accepted
Age groups: Child, Adult

Key inclusion criteria (6 listed)

Participant aged 9 to 60 years (i.e., from the day of the 9th birthday to the day prior to the 61th birthday) on the day of inclusion.
Participant in good health, based on medical history and physical examination.
Informed consent form (ICF) or assent form was signed and dated by the participant (based on local regulations), and/or ICF was signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations).
For participant aged 9 to 11 years: known (documented) receipt of at least 4 previous doses of diphtheria toxoid, tetanus toxoid and acellular pertussis-containing (DTaP) vaccines, with the last dose not within the last 5 years prior to enrolment.
OR For participant aged at least 12 years: known (documented or self-reported) receipt of at least 3 previous doses of diphtheria toxoid, tetanus toxoid, and whole cell pertussis-containing (DTwP) vaccines, with the last dose not within the last 5 years prior to enrolment.

Key exclusion criteria (16 listed)

Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination).
Participation 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.
Planned receipt of any vaccine in the 4 weeks following any trial vaccination.
Previous vaccination against dengue disease with the trial CYD dengue vaccine.
Receipt of immune globulins, blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response.

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: Dengvaxia®0.5 milliliter (mL), Subcutaneous at Month 1, 7 and Month 13, respectively	Biological	Concomitant Administration Group, Sequential Administration Group
Tdap: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine adsorbedAlso: Adacel®0.5 mL, intramuscularly (IM) at Month 1.	Biological	Concomitant Administration Group
Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbedAlso: Adacel®0.5 mL, intramuscularly at Day 0.	Biological	Sequential Administration Group

Primary outcome

Geometric Mean Concentrations (GMCs) of Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) 28 Days After Dose of Tdap Vaccine in Previously Dengue Immune Participants
Time frame: 28 days after Tdap vaccination
GMCs against each pertussis antigens (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], fimbriae types 2 and 3 [FIM2+3]) were assessed using an enzyme-linked immunosorbent assay (ELISA) method and were measured in ELISA unit/milliliter (EU/mL). Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants
Time frame: 28 days after Tdap vaccination
Seroprotection against diphtheria (Anti-D) and tetanus (Anti-T) antigens was performed by Micrometabolic Inhibition Test - Toxin Neutralization assay (MIT-TNA) and ELISA, respectively. Seroprotection was defined as anti-D and anti-T Ab concentration greater than 0.1 international units (IU)/mL. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Geometric Mean Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Time frame: 28 days after first CYD dengue vaccination
The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using the 50% plaque reduction neutralization test (PRNT50) assay method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Titers were measured in terms of 1/dilution.

12 secondary outcomes

Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Time frame: Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination
Percentage of Participants With Neutralizing Antibody Titers Against Each of the 4 Dengue Virus Serotypes of CYD at Baseline and 28 Days After First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Time frame: Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination
Percentage of Participants With Neutralizing Antibody Titers Above Predefined Thresholds Against at Least 1, 2, 3, or 4 Serotypes of CYD at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Time frame: Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination
Geometric Mean Concentrations of Serum Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) at Baseline and 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants
Time frame: Baseline (Pre-Tdap vaccination) and 28 days after the Tdap vaccination
Percentage of Participants Achieving Serum Antibody (>=0.1 IU/mL) Against Diphtheria and Tetanus Antigens at Baseline and 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants
Time frame: Baseline (Pre-Tdap vaccination) and 28 days after the dose of Tdap vaccination
Number of Participants With Immediate Unsolicited Adverse Events (AE) Following Vaccination With Tdap or CYD Dengue Vaccine
Time frame: Within 30 minutes after any and each vaccination
Number of Participants With Solicited Injection Site Reactions Following Vaccination With Tdap or CYD Dengue Vaccine
Time frame: Within 7 days after any and each vaccination
Number of Participants With Solicited Systemic Reactions Following Vaccination With Tdap or CYD Dengue Vaccine
Time frame: Within 14 days after any and each vaccination
Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With Tdap or CYD Dengue Vaccine
Time frame: Within 28 days after any and each vaccination
Number of Participants Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Tdap or CYD Dengue Vaccine
Time frame: Within 7 days post any and each vaccination
Number of Participants Reporting Serious Adverse Events (SAEs) and Serious AESIs Following Vaccination With Tdap or CYD Dengue Vaccine
Time frame: From Day 0 up to 6 months after the last Tdap or CYD vaccination
Number of Participants Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Tdap or CYD Dengue Vaccine
Time frame: From Day 0 up to 6 months after the last Tdap or CYD vaccination

Results and safety

Results posted to the registry on 27 Aug 2020, 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 + Tdap Vaccine (Concomitant Administration)	346	0
CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)	342	0

Primary outcome: Geometric Mean Concentrations (GMCs) of Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) 28 Days After Dose of Tdap Vaccine in Previously Dengue Immune Participants

Time frame: 28 days after Tdap vaccination. Geometric mean (95% Confidence Interval). Unit: EU/mL

Measure	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) n = 312	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration) n = 314
Anti-PT	65.2 (57.7 to 73.8)	76.0 (67.9 to 85.1)
Anti-FHA	273 (248 to 299)	267 (241 to 296)
Anti-PRN	50.6 (41.4 to 61.9)	44.9 (36.7 to 55.0)
Anti-FIM2+3	705 (586 to 847)	643 (537 to 770)

CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) vs CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration): GMC ratio: 0.848 (95% CI 0.721 to 0.997)
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) vs CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration): GMC ratio: 1.02 (95% CI 0.892 to 1.18)
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) vs CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration): GMC ratio: 1.11 (95% CI 0.836 to 1.46)

Population analysed: Per protocol analysis set of Tdap (PPT) included dengue immune participants who received at least one dose of Tdap and had no relevant protocol deviations. Here, 'Number analyzed' = participants with available data for each specified category.

Primary outcome: Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants

Time frame: 28 days after Tdap vaccination. Number (95% Confidence Interval). Unit: percentage of participants

Measure	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) n = 312	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration) n = 314
Anti-D	90.1 (86.2 to 93.1)	89.8 (85.9 to 92.9)
Anti-T	98.4 (96.3 to 99.5)	99.0 (97.2 to 99.8)

CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) vs CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration): Percentage difference: 0.26 (95% CI -4.53 to 5.04)
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) vs CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration): Percentage difference: -0.66 (95% CI -2.87 to 1.37)

Population analysed: Analysis was performed on PPT population. Here, 'Number analyzed' = participants with available data for each specified category.

Primary outcome: Geometric Mean Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants

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

Measure	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) n = 312	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration) n = 308
Serotype 1	513 (427 to 617)	461 (384 to 552)
Serotype 2	677 (588 to 780)	568 (489 to 661)
Serotype 3	653 (558 to 765)	706 (603 to 828)
Serotype 4	378 (324 to 442)	472 (404 to 551)

CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) vs CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration): GMT ratio: 1.11 (95% CI 0.862 to 1.44)
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) vs CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration): GMT ratio: 1.19 (95% CI 0.97 to 1.47)
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration) vs CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration): GMT ratio: 0.925 (95% CI 0.739 to 1.16)

Population analysed: Analysis was performed on per-protocol analysis set for CYD dengue vaccine (PPC) population which included dengue immune participants who received 1st dose of CYD dengue vaccine and had no relevant protocol deviations.

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: AE data were collected from Day 0 up to Day 28 post any vaccination. SR data were collected from Day 0 up to Day 14 post-vaccination. The SAEs were collected throughout the trial, i.e. up to 6 months after last Tdap or CYD vaccination.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	8 of 338 (2.4%)	248 of 338 (73.4%)	0 of 338
CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)	11 of 342 (3.2%)	263 of 342 (76.9%)	0 of 342

Limitations and caveats (from the sponsor): Due to absence of response of competent authorities from The Philippines on protocol amendment, the study was prematurely terminated before injection of last dose (3rd dose) of the CYD dengue vaccine. Objectives related to 3rd dose were not assessed.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34117198Santos J, Montellano ME, Solante R, Perreras N, Meyer S, Toh ML, Zocchetti C, Vigne C, Mascarenas C. Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Tdap Vaccine: Randomized Phase IIIb Trial in Healthy Participants 9-60 Years of Age in the Philippines. Pediatr Infect Dis J. 2021 Sep 1;40(9):856-863. doi: 10.1097/INF.0000000000003220.
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 SA

4 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 6 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: stopped early, as of the sponsor's last update on 25 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 4 sites in 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Aug 2020). 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?

Geometric Mean Concentrations (GMCs) of Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) 28 Days After Dose of Tdap Vaccine in Previously Dengue Immune Participants (time frame: 28 days after Tdap vaccination). The study lists 3 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 NCT02992418, which also lists 1 linked publication.

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 25 Mar 2022.