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

NCT02993757 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: CYD67U1111-1161-33762019-003135-36
• Study Type: interventional
• Target: 528
• Locations: 1 country
• Sites: 5

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.

Conditions

Dengue Fever; Dengue Hemorrhagic Fever; Human Papillomavirus Disease

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  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

  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

  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

  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

  Day 0 (pre-vaccination) and 28 days after each CYD dengue vaccination

Study Arms (2)

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.

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.

Biological: CYD Dengue Vaccine; Biological: Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.

Interventions

CYD Dengue Vaccine BIOLOGICAL

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

Also known as: Dengvaxia®

CYD Dengue Vaccine + Gardasil (Concomitant Administration)

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

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

Also known as: Gardasil®

CYD Dengue Vaccine + Gardasil (Concomitant Administration); CYD Dengue Vaccine + Gardasil (Sequential Administration)

Eligibility Criteria

• Age: 9 Years - 13 Years
• Sex: all
• 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 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.
• 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.

Sponsors & Collaborators

• Sanofi Pasteur, a Sanofi Company: lead

Study Sites (5)

Sanofi Pasteur Investigational Site 004

Klang, 42000, Malaysia

Location

Sanofi Pasteur Investigational Site 005

Kuala Lumpur, 50590, Malaysia

Location

Sanofi Pasteur Investigational Site 001

Kuala Lumpur, 59100, Malaysia

Location

Sanofi Pasteur Investigational Site 003

Kuantan, 25100, Malaysia

Location

Sanofi Pasteur Investigational Site 002

Sibu, 96000, Malaysia

Location

Related Publications (1)

• 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.

  PMID: 34250977 DERIVED

MeSH Terms

Conditions

Dengue; Severe Dengue

Interventions

Dengue Vaccines; Human Papillomavirus Recombinant Vaccine Quadrivalent, Types 6, 11, 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; Vaccines, Combined; Papillomavirus Vaccines

Limitations and Caveats

Change of population for non-inferiority reduced to dengue immune participants \& time window for 3rd vaccination not reached(study hold),hence non-inferiority analysis not performed \& immunogenicity was performed on FAS \& not on Per Protocol Set.

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: December 12, 2016
• First Posted: December 15, 2016
• Study Start: December 1, 2016
• Primary Completion: May 27, 2019
• Study Completion: May 27, 2019
• Last Updated: March 25, 2022
• Results First Posted: June 11, 2020

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

MY (5)