Study of a Booster Dose of a Tetravalent Dengue Vaccine in Subjects Who Previously Completed the 3-dose Schedule

Immunogenicity and Safety of a Tetravalent Dengue Vaccine Given as a Booster Injection in Adolescents and Adults Who Previously Completed the 3-dose Schedule in a Study Conducted in Latin America

The aim of the study was to assess and describe the booster effect of a CYD dengue vaccine dose administered 4 to 5 years after the completion of a 3-dose vaccination schedule.

Primary Objective

- To demonstrate the non-inferiority, in terms of geometric mean of titer ratios (GMTRs), of a CYD dengue vaccine booster compared to the third CYD dengue vaccine injection in participants from CYD13 - NCT00993447 and CYD30 - NCT01187433 trials (participants from Group 1 only).

Secondary Objectives:

• If the primary objective of non-inferiority was achieved: To demonstrate the superiority, in terms of GMTRs, of a CYD dengue vaccine booster compared to the third CYD dengue vaccine injection in participants from CYD13 and CYD30 trials.
• To describe the immune responses elicited by a CYD dengue vaccine booster and placebo injection in participants who received 3 doses of the CYD dengue vaccine in the CYD13 and CYD30 trials in all participants.
• To describe the neutralizing antibody levels of each dengue serotype post-dose 3 (CYD13 and CYD30 participants) and immediately prior to booster or placebo injection in all participants.
• To describe the neutralizing antibody persistence 6 months, 1 year, and 2 years post booster or placebo injection in all participants.
• To evaluate the safety of booster vaccination with the CYD dengue vaccine in all participants.

Study Overview

• Status: Completed
• Conditions: Dengue Fever; Dengue Hemorrhagic Fever
• Intervention / Treatment: Biological: CYD Dengue Vaccine (5-dose formulation); Biological: Placebo, NaCl 0.9%

Detailed Description

Healthy adolescents and adults who received 3 doses of the tetravalent dengue vaccine 4 to 5 years earlier in previous CYD dengue vaccine trials (CYD13 and CYD30) received either a booster dose CYD dengue vaccine or a placebo on Day 0. They were evaluated for safety and antibody persistence of the booster injection up to 2 years post-vaccination.

• Study Type: Interventional
• Enrollment (Actual): 251
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Vitoria, Brazil, 29040-091
    • Investigational Site Number 001
• Colombia
  • Bucaramanga, Colombia
    • Investigational Site Number 002
• Honduras
  • Tegucigalpa, Honduras
    • Investigational Site Number 003
• Mexico
  • Temixco, Mexico, 62587
    • Investigational Site Number 004
• Puerto Rico
  • Carolina, Puerto Rico, 984
    • Investigational Site Number 005

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years to 22 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Had been identified as a potential participant by the Sponsor and is included in the list provided to the Investigator (i.e., aged 9 to 16 years on the day of first vaccination of CYD dengue vaccine in CYD13/CYD30 and has a post-dose 3 serum sample available [at least 400 microliters of serum]).
• Participants were in good health, based on medical history and physical examination.
• Assent form or informed consent form (ICF) had been signed and dated by the participant (based on local regulations), and 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 and parent(s)/legally acceptable representative(s) attended all scheduled visits and complied with all trial procedures.

Exclusion Criteria:

• Participant who received any other dengue vaccination that was not part of the CYD13 or CYD30 trials.
• Participant was pregnant, or lactating, or of childbearing potential (to be considered of non childbearing potential, a female must be pre-menarche or post-menopausal for at least 1 year, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination).
• Participation at the time of study enrollment (or in the 4 weeks preceding the trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
• Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned receipt of any vaccine in the 4 weeks following the trial vaccination.
• Receipt of immune globulins, blood or blood-derived products in the past 3 months.
• Known or suspected congenital or acquired immunodeficiency; 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).
• 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.
• Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with trial conduct or completion.
• Receipt of blood or blood-derived products in the past 3 months, which might interfere with assessment of the immune response.
• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
• Current alcohol abuse or drug addiction.
• Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature >= 38.0°C). A prospective participant should not be included in the study until the condition had resolved or the febrile event had subsided.
• Identified as an Investigator or employee of the Investigator or study center 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CYD Dengue Vaccine Booster Group; Participants who received 3 doses of the tetravalent dengue vaccine in previous CYD dengue vaccine studies (CYD13 or CYD30), received a booster injection of CYD dengue vaccine at Day 0 in this study (CYD64).	Biological: CYD Dengue Vaccine (5-dose formulation); 0.5 mL, Subcutaneous
EXPERIMENTAL: Placebo Group; Participants who received 3 doses of the tetravalent dengue vaccine in previous CYD dengue vaccine studies (CYD13 or CYD30), received an injection of placebo at Day 0 in this study (CYD64).	Biological: Placebo, NaCl 0.9%; 0.5 mL, Subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Following Booster Injection With CYD Dengue Vaccine in CYD64 Compared to Third CYD Dengue Vaccine Received in CYD13/CYD30: CYD Dengue Vaccine Booster Group	Geometric Mean Titers (GMTs) of antibodies against each of the 4 dengue virus serotype (parental strains) were assessed using the plaque reduction neutralization test (PRNT).	28 days post-dose 3 in CYD13 or CYD30 and 28 days post-booster injection in CYD64

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
GMTs of Antibodies Against Each Dengue Virus Serotype Following Booster Injection With CYD Dengue Vaccine in CYD64 Compared to Third CYD Dengue Vaccine Received in CYD13/CYD30: CYD Dengue Vaccine Booster Group	GMTs of antibodies against each of the 4 dengue virus serotype (parental strains) following booster injection were assessed using PRNT.	28 days post-dose 3 in CYD13 or CYD30 and 28 days post-booster injection in CYD64
GMTs of Antibodies Against Each Dengue Virus Serotype Before And Following Booster Injection (Inj.) With Either CYD Dengue Vaccine or Placebo	GMTs of antibodies against each of the 4 dengue virus serotype (parental strains) following booster injection were assessed using PRNT.	Pre-booster injection (Day 0) and 28 days post-booster injection
GMTRs of Antibodies Against Each Dengue Virus Serotype Before and Following Booster Injection With Either CYD Dengue Vaccine or Placebo	GMTs of antibodies against each of the 4 dengue virus serotype (parental strains) following booster injection were assessed using PRNT. GMTRs were calculated as the ratio of GMTs post-booster injection and pre-booster injection.	Pre-booster injection (Day 0) and 28 days post-booster injection
Percentage of Participants With Seropositivity Against Each Dengue Virus Serotype Before and Following Booster Injection With Either CYD Dengue Vaccine or Placebo	Seropositivity against each dengue virus serotype were measured using dengue PRNT. Seropositive participants were defined as the participants with neutralizing antibody titers greater than or equal to (>=)10 (1/dilution).	Pre-booster injection (Day 0) and 28 days post-booster injection
Percentage of Participants With Seroconversion Against Each Dengue Virus Serotype Following Booster Injection With Either CYD Dengue Vaccine or Placebo	Seroconversion for each serotype was defined as the percentage of participants with either a pre-booster titer <10 (1/dilution) and a post-booster titer >=40 (1/dilution), or a pre-booster titer >=10 (1/dilution) and a >=4-fold increase in post-booster titer as determined by PRNT.	28 days post-booster injection
GMTs of Antibodies Against Each Dengue Virus Serotype Following the Third CYD Dengue Vaccine Injection Received in Study CYD13/CYD30, and Before Booster Injection With Either CYD Dengue Vaccine or Placebo	GMTs of antibodies against each of the 4 dengue virus serotype (parental strains) were assessed using the PRNT.	28 days post-dose 3 in CYD13 or CYD30 and pre-booster injection (Day 0) in CYD64
GMTRs of Antibodies Against Each Dengue Virus Serotype Following the Third CYD Dengue Vaccine Injection Received in Study CYD13/CYD30, and Before Booster Injection With Either CYD Dengue Vaccine or Placebo	GMTs of antibodies against each of the 4 dengue virus serotype (parental strains) were assessed using the PRNT. GMTRs were calculated as the ratio of GMTs pre-booster injection and post-dose injection.	28 days post-dose 3 in CYD13 or CYD30 and pre-booster injection (Day 0) in CYD64
Percentage of Participants With Seropositivity Against Each Dengue Virus Serotype Following the Third CYD Dengue Vaccine Injection Received in Study CYD13/CYD30, and Following Booster Injection With Either CYD Dengue Vaccine or Placebo	Seropositivity against each dengue virus serotype were measured using dengue PRNT. Seropositive participants were defined as the participants with neutralizing antibody titers >=10 (1/dilution).	28 days post-dose 3 in CYD13 or CYD30 and 28 days post-booster injection in CYD64
GMTs of Antibodies Against Each Dengue Virus Serotype Following Booster Injection With Either CYD Dengue Vaccine or Placebo	GMTs of antibodies against each of the 4 dengue virus serotype (parental strains) following booster injection were assessed using PRNT.	6 months,12 months, and 24 months post-booster injection in CYD64
GMTRs of Antibodies Against Each Dengue Virus Serotype Following Booster Injection With Either CYD Dengue Vaccine or Placebo	GMTs of antibodies against each of the 4 dengue virus serotype (parental strains) following booster injection were assessed using PRNT. GMTRs were calculated as the ratio of GMTs post-booster injection and pre-booster injection.	Pre-booster injection (Day 0), 6 months, 12 months, and 24 months post-booster injection in CYD64
Percentage of Participants With Seropositivity Against Each Dengue Virus Serotype Following Booster Injection With Either CYD Dengue Vaccine or Placebo	Seropositivity against each dengue virus serotype were measured using dengue PRNT. Seropositive participants were defined as the participants with neutralizing antibody titers >=10 (1/dilution).	6 months,12 months, and 24 months post-booster injection in CYD64
Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, Swelling) Following Booster Injection With Either CYD Dengue Vaccine or Placebo	Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 reactions: Pain: significant; prevents daily activity; Erythema and Swelling: >100 millimeters (mm).	Within 7 days after booster injection
Number of Participants Reporting Solicited Systemic Reactions (Fever, Headache, Malaise, Myalgia, Asthenia) Following Booster Injection With Either CYD Dengue Vaccine or Placebo	Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 reactions: Fever: >=39°C; Headache, Malaise, Myalgia, and Asthenia: significant, prevents daily activity.	Within 14 days after booster injection

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Coronel D, Garcia-Rivera EJ, Rivera M, Arredondo-Garcia JL, Dietze R, Perroud AP, Cortes M, Bonaparte M, Zhao J, Tila M, Jackson N, Zambrano B, Noriega F. Dengue Vaccine Booster in Healthy Adolescents and Adults in Latin America: Evaluation 4-5 Years After a Primary 3-Dose Schedule. Pediatr Infect Dis J. 2019 May;38(5):e90-e95. doi: 10.1097/INF.0000000000002286.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 14, 2016
• Primary Completion (ACTUAL): November 23, 2016
• Study Completion (ACTUAL): October 28, 2018

Study Registration Dates

• First Submitted: December 3, 2015
• First Submitted That Met QC Criteria: December 3, 2015
• First Posted (ESTIMATE): December 8, 2015

Study Record Updates

• Last Update Posted (ACTUAL): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Dengue Fever; Dengue Hemorrhagic Fever; Dengue virus; CYD Dengue Vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Wounds and Injuries; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Body Temperature Changes; Heat Stress Disorders; Hyperthermia; Fever; Hemorrhagic Fevers, Viral; Dengue; Severe Dengue
• Other Study ID Numbers: CYD64; U1111-1161-2855 (OTHER: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No