Clinical trial NCT02979535: Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Cervarix®
Official title: Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Cervarix® in Healthy Female Subjects Aged 9 to 14 Years in Mexico
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dengue Fever
Dengue Hemorrhagic Fever
Human Papillomavirus Disease
Keywords: Dengue Fever
Dengue Hemorrhagic Fever
Human Papillomavirus Disease
CYD Dengue Vaccine
Dengvaxia®
Cervarix®
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2016-12-01
Enrollment: 480
Sex: FEMALE
Minimum age (years): 9
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The aim of this study was to investigate the immunogenicity and safety of CYD dengue vaccine and Cervarix when administered concomitantly or sequentially in healthy female participants aged 9-14 years of age.

Primary objectives:

* To demonstrate that the humoral immune response (in terms of geometric mean titers \[GMTs\]) to Cervarix after concomitant administration with the CYD dengue vaccine is non-inferior to the humoral immune response (in terms of GMTs) after sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Cervarix.
* To demonstrate that the humoral immune response (in terms of GMTs) to the CYD dengue vaccine after concomitant administration with Cervarix is non-inferior to the humoral immune response (in terms of GMTs) to the CYD dengue vaccine after sequential administration with Cervarix 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 Cervarix after concomitant administration with the CYD dengue vaccine is non-inferior to the humoral immune response (in terms of seroconversion) to Cervarix sequential administration with the CYD dengue vaccine measured 28 days after the last dose of Cervarix.
* To describe the humoral immune response to Cervarix at baseline and after each dose of Cervarix 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 Cervarix and CYD dengue vaccine after each and any dose in each group.

Detailed description: Participants received 3 doses of the CYD dengue vaccine and 2 doses of Cervarix administered either concomitantly or sequentially. Due to a protocol amendment, only previously dengue exposed participants (seropositive for dengue before vaccination) were eligible to complete the vaccination schedule and be assessed for CYD immunogenicity and human papilloma virus (HPV) immunogenicity. Dengue unexposed participants (seronegative for dengue before vaccination) did not receive the third CYD dengue vaccine injection, but were followed for safety up to 6 months after the last injection.

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. All participants were included in the assessment of safety up to 6 months after the last injection.

Eligibility criteria: Inclusion Criteria:

* Female aged 9 to 14 years (i.e., from the day of the 9th birthday to the day prior to the 15th 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.

Exclusion Criteria:

* 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 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 HPV disease with either the trial vaccine or another vaccine.
* Receipt of immune globulins, blood or blood-derived products in the past 3 months.
* Known or suspected congenital or acquired immunodeficiency (including 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 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 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 Hepatitis B, Hepatitis C infection.

Primary outcomes:
measure: Geometric Mean Titers (GMTs) Against Each Cervarix Human Papillomavirus (HPV) Antigen (HPV-16 and HPV-18) 28 Days After Last Cervarix Vaccination in the Previously Dengue Seropositive Participants
timeFrame: 28 days after the last Cervarix vaccination
measure: GMTs Against Each Dengue Virus Serotype 28 Days After the Third CYD Dengue Vaccination in the Previously Dengue Seropositive Participants
timeFrame: 28 days after third CYD dengue vaccination
Secondary outcomes:
measure: GMTs Against Each Cervarix HPV Antigen (HPV-16 and HPV-18) at Day 0 and 28 Days After Each Cervarix Vaccination in the Previously Dengue Seropositive Participants
timeFrame: Day 0 and 28 days after each Cervarix vaccination
measure: Percentage of Participants With Seroconversion Against Each Cervarix HPV Antigen (HPV-16 and HPV-18) 28 Days After Each Dose of Cervarix Vaccination in the Previously Dengue Seropositive Participants
timeFrame: 28 days after each Cervarix vaccination
measure: GMTs 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 Seropositive Participants
timeFrame: Day 0 and 28 days after each CYD dengue vaccine vaccination
measure: Percentage of Participants With Neutralizing Antibody Titers >=10 (1/Dil) 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 Seropositive Participants
timeFrame: Day 0 and 28 days after each CYD dengue vaccine vaccination
measure: Percentage of Participants With Neutralizing Antibody Titers >=10 (1/Dil) Against At Least 1,2,3,or4 Dengue Virus Serotypes of CYD Dengue Vaccine at Day 0 And 28 Days After Each Dose of CYD Dengue Vaccination in Previously Dengue Seropositive Participants
timeFrame: Day 0 and 28 days after each CYD dengue vaccination
measure: Percentage of Participants With Neutralizing Antibody Titers Above Pre-defined Thresholds Against Each Dengue Virus Serotypes of CYD at Baseline And 28 Days After Each Dose of CYD Dengue Vaccination in Dengue Seropositive Participants
timeFrame: Day 0 and 28 days after each CYD dengue vaccination
measure: Number of Participants Reporting Immediate Adverse Events (AEs) Following Vaccination With Cervarix or CYD Dengue Vaccine
timeFrame: Within 30 minutes after each and any vaccination
measure: Number of Participants Reporting Solicited Injection Site Reactions Following Vaccination With Cervarix or CYD Dengue Vaccine
timeFrame: Up to 7 days after each and any vaccination
measure: Number of Participants Reporting Solicited Systemic Reactions Following Vaccination With Cervarix or CYD Dengue Vaccine
timeFrame: Up to 14 days after any and each vaccination
measure: Number of Participants Reporting Unsolicited AEs Following Vaccination With Cervarix or CYD Dengue Vaccine
timeFrame: Up to 28 days after any and each vaccination
measure: Number of Participants Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Cervarix or CYD Dengue Vaccine
timeFrame: Up to 7 days after any and each vaccination
measure: Number of Participants Reporting Serious Adverse Events (SAEs) Including Serious AESIs Following Vaccination With Cervarix or CYD Dengue Vaccine
timeFrame: From Day 0 up to 6 months after the last CYD or Cervarix vaccination
measure: Number of Participants Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Cervarix or CYD Dengue Vaccine
timeFrame: From Day 0 up to 6 months after the last CYD or Cervarix vaccination
Other outcomes:
Locations:
city: Mexico City
country: Mexico
Study officials:
affiliation: Sanofi Pasteur SA
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Arredondo JL, Villagomez Martinez SM, Concepcion Morales M, Meyer S, Toh ML, Zocchetti C, Vigne C, Mascarenas C. Immunogenicity and safety of a tetravalent dengue vaccine and a bivalent HPV vaccine given concomitantly or sequentially in girls aged 9 to 14 years in Mexico. Vaccine. 2021 Jun 8;39(25):3388-3396. doi: 10.1016/j.vaccine.2021.04.064. Epub 2021 May 13.