Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Cervarix®

NCT ID: NCT02979535

Last Updated: 2022-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 480 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-16
• Study Completion Date: 2019-03-25

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.

Conditions

Dengue Fever; Dengue Hemorrhagic Fever; Human Papillomavirus Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

CYD Dengue Vaccine + Cervarix (Concomitant Administration)

Participants received 3 doses of CYD dengue vaccine 0.5 milliliter (mL) subcutaneously (SC) at Day 0, Month 6, and Month 12 and 2 doses of Cervarix vaccine 0.5 mL Intramuscularly (IM) concomitantly with the 2 first doses of CYD dengue vaccine.

Group Type: EXPERIMENTAL

CYD Dengue Vaccine

Intervention Type: BIOLOGICAL

0.5 mL, SC at Day 0, Months 6 and 12

Human Papillomavirus Bivalent [Types 16 and 18] Vaccine, Recombinant

Intervention Type: BIOLOGICAL

0.5 mL, IM at Day 0 and Month 6

CYD Dengue Vaccine + Cervarix (Sequential Administration)

Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Month 1, Month 7, and Month 13 along with the 2 doses of Cervarix vaccine 0.5 mL IM at Day 0 and Month 6 sequentially (i.e., one month before) to each of the 2 first doses of CYD dengue vaccine.

Group Type: EXPERIMENTAL

CYD Dengue Vaccine

Intervention Type: BIOLOGICAL

0.5 mL, SC at Months 1, 7, and 13

Human Papillomavirus Bivalent [Types 16 and 18] Vaccine, Recombinant

Intervention Type: BIOLOGICAL

0.5 mL, IM at Day 0 and Month 6

Interventions

CYD Dengue Vaccine

0.5 mL, SC at Day 0, Months 6 and 12

Intervention Type: BIOLOGICAL

CYD Dengue Vaccine

0.5 mL, SC at Months 1, 7, and 13

Intervention Type: BIOLOGICAL

Human Papillomavirus Bivalent [Types 16 and 18] Vaccine, Recombinant

0.5 mL, IM at Day 0 and Month 6

Intervention Type: BIOLOGICAL

Human Papillomavirus Bivalent [Types 16 and 18] Vaccine, Recombinant

0.5 mL, IM at Day 0 and Month 6

Intervention Type: BIOLOGICAL

Other Intervention Names

Dengvaxia®; Dengvaxia®; Cervarix®; Cervarix®

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.

• Minimum Eligible Age: 9 Years
• Maximum Eligible Age: 14 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Sanofi Pasteur, a Sanofi Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Sanofi Pasteur SA

Locations

Mexico City, , Mexico

Countries

Mexico

References

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.

Reference Type: DERIVED

PMID: 33992441 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1161-3455

Identifier Type: OTHER

Identifier Source: secondary_id

2019-000994-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CYD71

Identifier Type: -

Identifier Source: org_study_id