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

NCT ID: NCT02993757

Last Updated: 2022-03-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 528 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-01
• Study Completion Date: 2019-05-27

Brief 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.

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.

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 + Gardasil (Concomitant Administration)

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.

Group Type: EXPERIMENTAL

CYD Dengue Vaccine

Intervention Type: BIOLOGICAL

0.5 mL, SC injection at Day 0, Month 6 and 12, respectively.

Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.

Intervention Type: BIOLOGICAL

0.5 mL, IM injection at Day 0 and Month 6, respectively.

CYD Dengue Vaccine + Gardasil (Sequential Administration)

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.

Group Type: EXPERIMENTAL

CYD Dengue Vaccine

Intervention Type: BIOLOGICAL

0.5 mL, SC injection at Month 1, 7 and 13, respectively.

Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.

Intervention Type: BIOLOGICAL

0.5 mL, IM injection at Day 0 and Month 6, respectively.

Interventions

CYD Dengue Vaccine

0.5 mL, SC injection at Day 0, Month 6 and 12, respectively.

Intervention Type: BIOLOGICAL

CYD Dengue Vaccine

0.5 mL, SC injection at Month 1, 7 and 13, respectively.

Intervention Type: BIOLOGICAL

Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.

0.5 mL, IM injection at Day 0 and Month 6, respectively.

Intervention Type: BIOLOGICAL

Other Intervention Names

Dengvaxia®; Dengvaxia®; Gardasil®

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.
• 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.

• Minimum Eligible Age: 9 Years
• Maximum Eligible Age: 13 Years
• Eligible Sex: ALL
• 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

Sanofi Pasteur Investigational Site 004

Klang, , Malaysia

Sanofi Pasteur Investigational Site 005

Kuala Lumpur, , Malaysia

Sanofi Pasteur Investigational Site 001

Kuala Lumpur, , Malaysia

Sanofi Pasteur Investigational Site 003

Kuantan, , Malaysia

Sanofi Pasteur Investigational Site 002

Sibu, , Malaysia

Countries

Malaysia

References

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.

Reference Type: DERIVED

PMID: 34250977 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1161-3376

Identifier Type: OTHER

Identifier Source: secondary_id

2019-003135-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CYD67

Identifier Type: -

Identifier Source: org_study_id