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

NCT02979535 | Completed Phase 3 Results DMC

• 3 other identifiers: CYD71U1111-1161-34552019-000994-22
• Study Type: interventional
• Target: 480
• Locations: 1 country
• Sites: 1

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.

Conditions

Dengue Fever; Dengue Hemorrhagic Fever; Human Papillomavirus Disease

Keywords

Dengue Fever; Dengue Hemorrhagic Fever; Human Papillomavirus Disease; CYD Dengue Vaccine; Dengvaxia®; Cervarix®

Outcome Measures

Primary Outcomes (2)

• 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

  GMTs against each Cervarix HPV antigen (HPV-16 and HPV-18) were assessed using an enzyme-linked immunosorbent assay (ELISA) method. Dengue seropositive participants at baseline were defined as those participants with titers greater than or equal to (\>=) 10 (1/dilutions \[dil\]) for at least one serotype with the parental dengue virus strain.

  28 days after the last Cervarix vaccination

• GMTs Against Each Dengue Virus Serotype 28 Days After the Third CYD Dengue Vaccination in the Previously Dengue Seropositive Participants

  The GMTs against each of the four parental dengue virus serotypes (Serotypes 1, 2, 3, and 4) of CYD dengue vaccine were assessed using the 50% plaque reduction neutralization test (PRNT50) assay. Dengue seropositive participants at baseline were defined as those participants with titers \>=10 (1/dil) for at least one serotype with the parental dengue virus strain.

  28 days after third CYD dengue vaccination

Secondary Outcomes (13)

• 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

  Day 0 and 28 days after each Cervarix vaccination

• 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

  28 days after each Cervarix vaccination

• 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

  Day 0 and 28 days after each CYD dengue vaccine vaccination

• 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

  Day 0 and 28 days after each CYD dengue vaccine vaccination

• 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

  Day 0 and 28 days after each CYD dengue vaccination

Study Arms (2)

CYD Dengue Vaccine + Cervarix (Concomitant Administration)

EXPERIMENTAL

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.

Biological: CYD Dengue Vaccine; Biological: Human Papillomavirus Bivalent [Types 16 and 18] Vaccine, Recombinant

CYD Dengue Vaccine + Cervarix (Sequential Administration)

EXPERIMENTAL

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.

Biological: CYD Dengue Vaccine; Biological: Human Papillomavirus Bivalent [Types 16 and 18] Vaccine, Recombinant

Interventions

CYD Dengue Vaccine BIOLOGICAL

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

Also known as: Dengvaxia®

CYD Dengue Vaccine + Cervarix (Concomitant Administration)

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

0.5 mL, IM at Day 0 and Month 6

Also known as: Cervarix®

CYD Dengue Vaccine + Cervarix (Concomitant Administration)

Eligibility Criteria

• Age: 9 Years - 14 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (1)

Unknown Facility

Mexico City, Mexico

Location

Related Publications (1)

• 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.

  PMID: 33992441 DERIVED

MeSH Terms

Conditions

Dengue; Severe Dengue

Interventions

Dengue Vaccines; human papillomavirus vaccine, L1 type 16, 18

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Limitations and Caveats

Change of population for non-inferiority reduced to dengue seropositive participants and time window for vaccination not reached (study hold), hence non-inferiority analysis not performed \& immunogenicity analysis was performed on FAS \& not on PPS.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi Pasteur

Contact-US@sanofi.com

800-633-1610

Study Officials

• Medical Director

  Sanofi Pasteur SA

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 29, 2016
• First Posted: December 1, 2016
• Study Start: November 16, 2016
• Primary Completion: March 25, 2019
• Study Completion: March 25, 2019
• Last Updated: March 25, 2022
• Results First Posted: March 9, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

ME (1)