Dengue FeverPhase 3NCT02993757
Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Gardasil®
A Phase 3 study testing CYD Dengue Vaccine and Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant. in people with Dengue Fever and Dengue Hemorrhagic Fever, run by Sanofi Pasteur, a Sanofi Company at 5 sites in Malaysia.
Trial summary
The aim of the study was to assess the safety and immunogenicity of the CYD dengue vaccine and Gardasil (Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant) when administered concomitantly or sequentially. Read more about this study
- Who is it for?
- Ages 9 to 13 yearsHealthy volunteers can take part
- Conditions the study is for
- Dengue Fever, Dengue Hemorrhagic Fever, Human Papillomavirus Disease
- What is being tested?
- CYD Dengue Vaccine and Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 528 participants
- Where
- 5 sitesMalaysia
- Study dates
- 1 Dec 2016to 27 May 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 13 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Participants aged 9 to 13 years (i.e., from the day of the 9th birthday to the day prior to the 14th birthday) on the day of inclusion.
- Informed consent form (ICF) or Assent form (AF) had been signed and dated by the participant (based on local regulations), and/or 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 (or participant and parent[s] or another legally acceptable representative) was (were) able to attend all scheduled visits and complied with all trial procedures.
- Participant in good health, based on medical history, and physical examination.
Who cannot join
- Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female had to be pre-menarche, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and 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 vaccine.
- Previous vaccination against human papillomavirus (HPV) disease with either the trial vaccine or another vaccine.
- Receipt of immune globulins, blood or blood-derived products in the past 3 months.
Show all 16Show fewer
- Known or suspected congenital or acquired immunodeficiency (including human immunodeficiency virus 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 corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
- History of HPV infection, confirmed either clinically, serologically, or microbiologically as reported by participant or parent(s) or another legally acceptable representative.
- Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the trial or to a vaccine containing any of the same substances.
- Thrombocytopenia, contraindicating IM vaccination.
- Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination.
- 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 interfered 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 interfered 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 Hepatitis B, Hepatitis C infection.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Malaysia5 sites
Sanofi Pasteur Investigational Site 004
Klang, 42000
Sanofi Pasteur Investigational Site 005
Kuala Lumpur, 50590
Sanofi Pasteur Investigational Site 001
Kuala Lumpur, 59100
Sanofi Pasteur Investigational Site 003
Kuantan, 25100
Sanofi Pasteur Investigational Site 002
Sibu, 96000
About this study
Official title: Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Gardasil® in Healthy Subjects Aged 9 to 13 Years in Malaysia
The aim of the study was to assess the safety and immunogenicity of the CYD dengue vaccine and Gardasil (Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant) when administered concomitantly or sequentially.
Primary objectives:
Read more
- To demonstrate that the humoral immune response (in terms of geometric mean titers [GMTs]) to Gardasil after concomitant administration was non-inferior to sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Gardasil.
- To demonstrate that the humoral immune response to the CYD dengue vaccine after concomitant administration was non-inferior to sequential administration with Gardasil measured 28 days after the last dose of the CYD dengue vaccine.
Secondary Objectives:
- To demonstrate that the humoral immune response (in terms of seroconversion) to Gardasil vaccine after concomitant administration was non-inferior to sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Gardasil.
- To describe the humoral immune response to Gardasil at baseline and after each dose of Gardasil in each and any group.
- To describe the humoral immune response to the CYD dengue vaccine at baseline and after each dose of the CYD dengue vaccine in each and any group.
- To describe the safety of Gardasil and the CYD dengue vaccine after each and any dose in each group.
Read the detailed description
Participants received 3 doses of CYD dengue vaccine and 2 doses of Gardasil administered either concomitantly or sequentially.
The study activities were put on hold for several months (up to 6 months for some participants) to obtain the approval of Protocol Amendment 1 by the competent authorities and completed the associated logistic tasks. Due to this protocol amendment as per Independent Data Monitoring Committee recommendation, only previously dengue immune participants (seropositive for dengue before vaccination) were eligible to complete the vaccination schedule. Dengue non-immune participants (seronegative for dengue before vaccination) did not receive any additional CYD dengue vaccine injections, but were followed for safety up to 6 months after the last injection.
Due to the change in amendment 1, the number of evaluable dengue immune participants at baseline did not meet the predefined number of participants that would have allowed for a global power of at least 80% for non-inferiority testing of Gardasil vaccine and CYD dengue vaccine (121 per group for the co-primary objectives and 194 per group for the secondary objectives).
All participants were assessed for immunogenicity and safety. Safety assessments included solicited reactions within 7 or 14 days after each injection, unsolicited adverse events (AEs) within 28 days after each injection, non-serious AEs of Special Interests (AESIs) within 7 days after each injection, and serious adverse events including AESI and hospitalized virologically-confirmed dengue cases during the study period.
- Being tested
- CYD Dengue Vaccine, Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.
- Keywords
- Dengue Fever, Dengue Hemorrhagic Fever, Human Papillomavirus Disease, CYD Dengue Vaccine, Dengvaxia®, Gardasil®
- Medical subject headings
- Dengue, Severe Dengue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYD Dengue VaccineBiological
Also called Dengvaxia®
0.5 mL, SC injection at Day 0, Month 6 and 12, respectively.
CYD Dengue VaccineBiological
Also called Dengvaxia®
0.5 mL, SC injection at Month 1, 7 and 13, respectively.
Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.Biological
Also called Gardasil®
0.5 mL, IM injection at Day 0 and Month 6, respectively.
| Study group | Role | What they receive |
|---|---|---|
| CYD Dengue Vaccine + Gardasil (Concomitant Administration) | Experimental | Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 milliliter (mL) subcutaneously (SC) at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL Intramuscular (IM), concomitantly with the first 2 doses of CYD dengue vaccine. Receives: Biological: CYD Dengue Vaccine; Biological: Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant. |
| CYD Dengue Vaccine + Gardasil (Sequential Administration) | Experimental | Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine. Receives: Biological: CYD Dengue Vaccine; Biological: Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Geometric Mean Titers (GMTs) Against Each Gardasil Vaccine Human Papillomavirus (HPV) Antigen (HPV-6, HPV-11, HPV-16, HPV-18) 28 Days After Last Gardasil Vaccination in the Previously Dengue Immune Participants
GMTs (measured in milli-Merck Units per mL [mMU/mL]) against each Gardasil HPV antigen (HPV-6, HPV-11, HPV-16, HPV-18) were assessed using competitive Luminex immunoassay (cLIA) method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Measured: 28 days after the last Gardasil vaccination
Geometric Mean Titers Against Each Parental Dengue Virus Serotype 28 Days After Third CYD Dengue Vaccination in the Previously Dengue Immune Participants
The GMTs against each of the four parental dengue virus serotypes (1, 2, 3, and 4) of CYD dengue vaccine was assessed using the 50% plaque reduction neutralization test (PRNT50) assay. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Measured: 28 days after third CYD dengue vaccination
Secondary outcomes (12)
Percentage of Participants With Seroconversion Against Each Gardasil HPV Antigen (HPV-6, HPV-11, HPV-16, HPV-18) 28 Days After Last Dose of Gardasil in the Previously Dengue Immune Participants
Neutralizing antibodies against each Gardasil HPV antigen (HPV-6, HPV-11, HPV-16, HPV-18) was assessed using cLIA method. Seroconversion was defined as changing serostatus from seronegative at baseline to seropositive (participants with a pre-vaccination titer < lower limit of quantification [LLOQ] (mMU/mL) to a post-vaccination titer >=LLOQ) or >=4-fold rise in antibody titer if seropositive at baseline. The LLOQ for HPV-6 and HPV-16 was 11 mMU/mL, 8 mMU/mL for HPV-11, and 10 mMU/mL for HPV-18. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Measured: 28 days after the last Gardasil vaccination
Geometric Mean Titers Against Each Gardasil HPV Antigen (HPV-6, HPV-11, HPV-16, HPV-18) at Day 0 and 28 Days After Each Dose of Gardasil in the Previously Dengue Immune Participants
The GMTs (measured in mMU/mL) against each Gardasil HPV antigen (HPV-6, HPV-11, HPV-16, HPV-18) was assessed using cLIA method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Measured: Day 0 (pre-vaccination) and 28 days after Gardasil vaccination 1 and 2
Geometric Mean Titers Against Each Dengue Virus Serotype of CYD Dengue Vaccine at Day 0 and 28 Days After Each Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
The GMTs against each of the four parental dengue virus serotypes (1, 2, 3, and 4) of CYD dengue vaccine was assessed using the PRNT50 assay. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Measured: Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination
Percentage of Participants With Neutralizing Antibody Titers Against Each of the 4 Dengue Virus Serotypes of CYD Dengue Vaccine at Day 0 And 28 Days After Each 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) was measured by PRNT50. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Measured: Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination
Percentage of Participants With Neutralizing Antibody Titers Above Pre-defined Thresholds Against at Least 1,2,3,or4 Serotypes of CYD Dengue Vaccine at Day 0 And 28 Days After Each Dose of CYD Dengue Vaccination in Previously Dengue Immune Participants
Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (1, 2, 3, and 4) was measured by PRNT50. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains. Percentage of participants with neutralizing antibody titers above pre-defined thresholds (>=10 and >=100 [1/dil]) against at least 1, 2, 3, or 4 serotypes of CYD dengue vaccine were reported.
Measured: Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination
Number of Participants Reporting Immediate Adverse Events (AEs) Following Vaccination With Gardasil or CYD Dengue Vaccine
Any unsolicited systemic AE occurred during the first 30 minutes post-vaccination was recorded on the case report form (CRF) as immediate AE. At Visit 1 and Visit 4, participants from Group 1 received both Gardasil and CYD vaccination and participants from Group 2 received only Gardasil vaccination. At Visit 2 and Visit 5, only participants from Group 2 received CYD vaccination whereas the participants from Group 1 received no vaccination.
Measured: Within 30 minutes after any and each vaccination
Number of Participants Reporting Solicited Injection Site Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine
A solicited reaction (SR) was an adverse reaction (AR) 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 pain, erythema, and swelling.
Measured: Up to 7 days after any and each vaccination
Number of Participants Reporting Solicited Systemic Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine
A SR was an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia. At Visit 1 and Visit 4, participants from Group 1 received both Gardasil and CYD vaccination and participants from Group 2 received only Gardasil vaccination. At Visit 2 and Visit 5, only participants from Group 2 received CYD vaccination whereas the participants from Group 1 received no vaccination.
Measured: Up to 14 days after any and each vaccination
Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With Gardasil or CYD Dengue Vaccine
An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRF in terms of diagnosis and/or onset post-vaccination. At Visit 1 and Visit 4, participants from Group 1 received both Gardasil and CYD vaccination and participants from Group 2 received only Gardasil vaccination. At Visit 2 and Visit 5, only participants from Group 2 received CYD vaccination whereas the participants from Group 1 received no vaccination.
Measured: Up to 28 days after any and each vaccination
Number of Participants Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Gardasil or CYD Dengue Vaccine
AESI were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine. At Visit 1 and Visit 4, participants from Group 1 received both Gardasil and CYD vaccination and participants from Group 2 received only Gardasil vaccination. At Visit 2 and Visit 5, only participants from Group 2 received CYD vaccination whereas the participants from Group 1 received no vaccination.
Measured: Within 7 days after any and each vaccination
Number of Participants Reporting Serious Adverse Events (SAEs) Including Serious Adverse Event of Special Interests Following Vaccination With Gardasil or CYD Dengue Vaccine
SAEs were AEs that resulted in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly or a medically important event. An AESIs 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 up to 6 months after the last Gardasil or CYD vaccination
Number of Participants Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Gardasil 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 enzyme-linked immunosorbent assay and/or dengue reverse transcriptase-polymerase chain reactions.
Measured: From Day 0 up to 6 months after the last Gardasil or CYD vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2016 (estimated)
- Study start1 Dec 2016
- Primary completion27 May 2019
- Study completion27 May 2019
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
- 528 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi Pasteur, a Sanofi Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Sanofi Pasteur SA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02993757
- Sponsor's protocol ID
- CYD67
- Other IDs
- U1111-1161-3376, 2019-003135-36, 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
Hassan J, Toh TH, Sivapunniam SK, Hasim R, Ghazali NF, Sulaiman S, Koh MT, Meyer S, Toh ML, Zocchetti C, Vigne C, Mascarenas C. Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Quadrivalent Human Papillomavirus Vaccine in Boys and Girls 9-13 Years of Age in Malaysia: A Phase IIIb, Randomized, Open-label Study. Pediatr Infect Dis J. 2021 Aug 1;40(8):774-781. doi: 10.1097/INF.0000000000003164.
PubMed 34250977
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 Gardasil® in Healthy Subjects Aged 9 to 13 Years in Malaysia
- ClinicalTrials.gov ID
- NCT02993757
- Acronym / sponsor ID
- CYD67
- Keywords
- Dengue Fever, Dengue Hemorrhagic Fever, Human Papillomavirus Disease, CYD Dengue Vaccine, Dengvaxia®, Gardasil®
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 528 participants (actual)
- Lead sponsor
- Sanofi Pasteur, a Sanofi CompanyIndustry (pharma, biotech, devices)
- Study start
- 1 Dec 2016 (actual)
- Primary completion
- 27 May 2019 (actual)
- Study completion
- 27 May 2019 (actual)
- First posted
- 15 Dec 2016 (estimated)
- Results
- Posted 11 Jun 2020
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 safety and immunogenicity of the CYD dengue vaccine and Gardasil (Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant) when administered concomitantly or sequentially.
Primary objectives:
- To demonstrate that the humoral immune response (in terms of geometric mean titers [GMTs]) to Gardasil after concomitant administration was non-inferior to sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Gardasil.
- To demonstrate that the humoral immune response to the CYD dengue vaccine after concomitant administration was non-inferior to sequential administration with Gardasil measured 28 days after the last dose of the CYD dengue vaccine.
Secondary Objectives:
- To demonstrate that the humoral immune response (in terms of seroconversion) to Gardasil vaccine after concomitant administration was non-inferior to sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Gardasil.
- To describe the humoral immune response to Gardasil at baseline and after each dose of Gardasil in each and any group.
- To describe the humoral immune response to the CYD dengue vaccine at baseline and after each dose of the CYD dengue vaccine in each and any group.
- To describe the safety of Gardasil and the CYD dengue vaccine after each and any dose in each group.
Detailed description
Participants received 3 doses of CYD dengue vaccine and 2 doses of Gardasil administered either concomitantly or sequentially.
The study activities were put on hold for several months (up to 6 months for some participants) to obtain the approval of Protocol Amendment 1 by the competent authorities and completed the associated logistic tasks. Due to this protocol amendment as per Independent Data Monitoring Committee recommendation, only previously dengue immune participants (seropositive for dengue before vaccination) were eligible to complete the vaccination schedule. Dengue non-immune participants (seronegative for dengue before vaccination) did not receive any additional CYD dengue vaccine injections, but were followed for safety up to 6 months after the last injection.
Due to the change in amendment 1, the number of evaluable dengue immune participants at baseline did not meet the predefined number of participants that would have allowed for a global power of at least 80% for non-inferiority testing of Gardasil vaccine and CYD dengue vaccine (121 per group for the co-primary objectives and 194 per group for the secondary objectives).
All participants were assessed for immunogenicity and safety. Safety assessments included solicited reactions within 7 or 14 days after each injection, unsolicited adverse events (AEs) within 28 days after each injection, non-serious AEs of Special Interests (AESIs) within 7 days after each injection, and serious adverse events including AESI and hospitalized virologically-confirmed dengue cases during the study period.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| CYD Dengue Vaccine + Gardasil (Concomitant Administration) | Experimental | Biological: CYD Dengue Vaccine, Biological: Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 milliliter (mL) subcutaneously (SC) at Day 0, Month 6, and Month 12; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Day 0 and Month 6. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL Intramuscular (IM), concomitantly with the first 2 doses of CYD dengue vaccine. |
| CYD Dengue Vaccine + Gardasil (Sequential Administration) | Experimental | Biological: CYD Dengue Vaccine, Biological: Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.Dengue immune participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13; whereas dengue non-immune participants received only 2 doses of CYD vaccine at Month 1 and Month 7. Both immune and non-immune participants received 2 doses of Gardasil vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the first 2 doses of CYD dengue vaccine. |
Who may qualify
- Ages
- 9 to 13 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Participants aged 9 to 13 years (i.e., from the day of the 9th birthday to the day prior to the 14th birthday) on the day of inclusion.
- Informed consent form (ICF) or Assent form (AF) had been signed and dated by the participant (based on local regulations), and/or 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 (or participant and parent[s] or another legally acceptable representative) was (were) able to attend all scheduled visits and complied with all trial procedures.
- Participant in good health, based on medical history, and physical examination.
Key exclusion criteria (16 listed)
- Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female had to be pre-menarche, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and 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 vaccine.
- Previous vaccination against human papillomavirus (HPV) disease with either the trial vaccine or another vaccine.
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 mL, SC injection at Day 0, Month 6 and 12, respectively. | Biological | CYD Dengue Vaccine + Gardasil (Concomitant Administration) |
| CYD Dengue VaccineAlso: Dengvaxia®0.5 mL, SC injection at Month 1, 7 and 13, respectively. | Biological | CYD Dengue Vaccine + Gardasil (Sequential Administration) |
| Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.Also: Gardasil®0.5 mL, IM injection at Day 0 and Month 6, respectively. | Biological | CYD Dengue Vaccine + Gardasil (Concomitant Administration), CYD Dengue Vaccine + Gardasil (Sequential Administration) |
Primary outcome
Geometric Mean Titers (GMTs) Against Each Gardasil Vaccine Human Papillomavirus (HPV) Antigen (HPV-6, HPV-11, HPV-16, HPV-18) 28 Days After Last Gardasil Vaccination in the Previously Dengue Immune Participants
Time frame: 28 days after the last Gardasil vaccination
GMTs (measured in milli-Merck Units per mL [mMU/mL]) against each Gardasil HPV antigen (HPV-6, HPV-11, HPV-16, HPV-18) were assessed using competitive Luminex immunoassay (cLIA) method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
Geometric Mean Titers Against Each Parental Dengue Virus Serotype 28 Days After Third CYD Dengue Vaccination in the Previously Dengue Immune Participants
Time frame: 28 days after third CYD dengue vaccination
The GMTs against each of the four parental dengue virus serotypes (1, 2, 3, and 4) of CYD dengue vaccine was assessed using the 50% plaque reduction neutralization test (PRNT50) assay. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains.
12 secondary outcomes
Percentage of Participants With Seroconversion Against Each Gardasil HPV Antigen (HPV-6, HPV-11, HPV-16, HPV-18) 28 Days After Last Dose of Gardasil in the Previously Dengue Immune Participants
Time frame: 28 days after the last Gardasil vaccination
Geometric Mean Titers Against Each Gardasil HPV Antigen (HPV-6, HPV-11, HPV-16, HPV-18) at Day 0 and 28 Days After Each Dose of Gardasil in the Previously Dengue Immune Participants
Time frame: Day 0 (pre-vaccination) and 28 days after Gardasil vaccination 1 and 2
Geometric Mean Titers Against Each Dengue Virus Serotype of CYD Dengue Vaccine at Day 0 and 28 Days After Each Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Time frame: Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination
Percentage of Participants With Neutralizing Antibody Titers Against Each of the 4 Dengue Virus Serotypes of CYD Dengue Vaccine at Day 0 And 28 Days After Each Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Time frame: Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination
Percentage of Participants With Neutralizing Antibody Titers Above Pre-defined Thresholds Against at Least 1,2,3,or4 Serotypes of CYD Dengue Vaccine at Day 0 And 28 Days After Each Dose of CYD Dengue Vaccination in Previously Dengue Immune Participants
Time frame: Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination
Number of Participants Reporting Immediate Adverse Events (AEs) Following Vaccination With Gardasil or CYD Dengue Vaccine
Time frame: Within 30 minutes after any and each vaccination
Number of Participants Reporting Solicited Injection Site Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine
Time frame: Up to 7 days after any and each vaccination
Number of Participants Reporting Solicited Systemic Reactions Following Vaccination With Gardasil or CYD Dengue Vaccine
Time frame: Up to 14 days after any and each vaccination
Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With Gardasil or CYD Dengue Vaccine
Time frame: Up to 28 days after any and each vaccination
Number of Participants Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Gardasil or CYD Dengue Vaccine
Time frame: Within 7 days after any and each vaccination
Number of Participants Reporting Serious Adverse Events (SAEs) Including Serious Adverse Event of Special Interests Following Vaccination With Gardasil or CYD Dengue Vaccine
Time frame: From Day 0 up to 6 months after the last Gardasil or CYD vaccination
Number of Participants Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Gardasil or CYD Dengue Vaccine
Time frame: From Day 0 up to 6 months after the last Gardasil or CYD vaccination
Results and safety
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 34250977Hassan J, Toh TH, Sivapunniam SK, Hasim R, Ghazali NF, Sulaiman S, Koh MT, Meyer S, Toh ML, Zocchetti C, Vigne C, Mascarenas C. Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Quadrivalent Human Papillomavirus Vaccine in Boys and Girls 9-13 Years of Age in Malaysia: A Phase IIIb, Randomized, Open-label Study. Pediatr Infect Dis J. 2021 Aug 1;40(8):774-781. doi: 10.1097/INF.0000000000003164.
- 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
Related trials for Dengue Fever
Active, not recruitingPhase 3
A Study to Evaluate V181 Dengue Vaccine in Healthy Participants 2 to 17 Years of Age (V181-005/MOBILIZE-1)
Healthy
RecruitingPhase 1
Phase 1 Challenge Study Using rDEN2delta30-7169 to Evaluate Host-Pathogen Interactions in Primary, Homotypic, and Heterotypic Dengue Virus Infection
Healthy Volunteers, Dengue
Active, not recruiting
A Controlled Human Infection Model of Dengue
Dengue
RecruitingPhase 2/3
Emetine for Viral Outbreaks (a.k.a. EVOLVE Antiviral Initiative)
Dengue
RecruitingPhase 2
Adaptive Dengue Antiviral Platform Trial
Dengue, Antiviral Drugs
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
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing CYD Dengue Vaccine and Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant. in people with Dengue Fever and Dengue Hemorrhagic Fever, run by Sanofi Pasteur, a Sanofi Company at 5 sites in Malaysia.
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 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 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 5 sites in Malaysia. 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 11 Jun 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 Titers (GMTs) Against Each Gardasil Vaccine Human Papillomavirus (HPV) Antigen (HPV-6, HPV-11, HPV-16, HPV-18) 28 Days After Last Gardasil Vaccination in the Previously Dengue Immune Participants (time frame: 28 days after the last Gardasil vaccination). The study lists 2 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 NCT02993757, 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.