Immunogenicity and Safety of Sanofi Pasteur's CYD Dengue Vaccine in Healthy Children and Adolescents in Latin America

Immunogenicity and Safety of Sanofi Pasteur's CYD Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America

Primary objectives:

• To describe the immune response to each dengue serotype before and after each vaccination with sanofi pasteur's CYD dengue vaccine.
• To evaluate the safety of each vaccination with sanofi pasteur's CYD dengue vaccine.

Study Overview

• Status: Completed
• Conditions: Dengue; Dengue Fever; Dengue Hemorrhagic Fever; Dengue Virus
• Intervention / Treatment: Biological: CYD Dengue Vaccine; Biological: Tetanus Toxoid Reduced Diphtheria Toxoid Acellular Pertussis

Detailed Description

The antibody levels against each serotype will be measured before and after each vaccination. The subjects will be followed for 28 days after each vaccination for solicited and unsolicited safety parameters. Serious adverse events (SAEs) will be collected throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 2

Contacts and Locations

Study Locations

• Colombia
  • Bucaramanga, Colombia
• Honduras
  • Tegucigalpa, Honduras
• Mexico
  • Cuernavaca, Mexico
• Puerto Rico
  • San Juan, Puerto Rico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 16 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria :

• Aged 9 to 16 years on the day of inclusion
• Subject in good health, based on medical history and physical examination
• Provision of assent form/informed consent form signed by the subject and by the parent(s) or another legally acceptable representative
• Subject and parent(s)/legally acceptable representative(s) able to attend all scheduled visits and to comply with all trial procedures
• For a female subject of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks prior to first vaccination until at least 4 weeks after the last vaccination.

Exclusion Criteria :

• Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia
• For a female subject of child-bearing potential, known pregnancy or positive urine pregnancy test at Visit 1
• Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination
• Breast-feeding woman
• Planned participation in another clinical trial during the present trial period
• Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroids therapy
• Known systemic hypersensitivity to any of the components of any of the trial vaccines or history of a life-threatening reaction to any of the trial vaccines or to a vaccine containing any of the same substances
• Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator
• Current alcohol abuse or drug addiction that may interfere with the subject's ability to comply with trial procedures
• Receipt of blood or blood-derived products in the preceding 3 months that might interfere with the assessment of immune response
• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination
• Planned receipt of any vaccine in the 4 weeks following the first trial vaccination
• Subject deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized without his/her consent
• Febrile illness (temperature ≥38.0°C) or moderate or severe acute illness/infection on the day of vaccination, according to investigator judgment
• Thrombocytopenia, bleeding disorder or anticoagulants in the 3 weeks preceding inclusion contraindicating intramuscular vaccination
• Severe diseases with or without fever, convulsions or neurological abnormalities without treatment or in progression.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CYD Dengue Vaccine Group; Sanofi pasteur's CYD Dengue vaccine group (Dengvaxia®)	Biological: CYD Dengue Vaccine; 0.5 mL, Subcutaneous at Day 0, 6 and 12 months; Other Names: Dengvaxia®
Sham Comparator: Control Vaccine Group	Biological: Tetanus Toxoid Reduced Diphtheria Toxoid Acellular Pertussis; NaCl: 0.5 mL, Intramuscular at Day 0 and 6 months; Adacel®: 0.5 mL, Intramuscular at 12 months; Other Names: NaCl; ADACEL®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Antibody Titers of ≥10 1/Dil Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT).	Day 0 (pre-each vaccination) and Day 28 post-each vaccination
Percentage of Flavi Virus-Immune Participants at Baseline With Antibody Titers ≥10 1/Dil Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavi virus (FV) immune participants at baseline are defined as those participants with ≥ 10 1/dil for at least one serotype with the parental dengue virus strain or for Yellow Fever titer.	Day 0 (pre-each vaccination) and Day 28 post-each vaccination
Percentage of Flavi Virus-Naive Participants at Baseline With Antibody Titers ≥10 1/Dil Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavi virus (FV) naïve participants are defined as those participants with < 10 1/dil for all serotypes with parental dengue virus strains and for Yellow Fever titer.	Day 0 (pre-each vaccination) and Day 28 post-each vaccination
Percentage of Participants With Antibody Titers of ≥10 1/Dil Against At Least 1, 2, 3, or 4 Serotypes With Parental Dengue Virus Strain Before and Following Each Injection With Either Sanofi Pasteur's CYD Dengue Vaccine or A Placebo Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT).	Day 0 (before each vaccination) and Day 28 post each vaccination
Percentage of Flavi Virus-Immune Participants With Antibody Titers of ≥10 1/Dil Against At Least 1, 2, 3, or 4 Serotypes With Parental Dengue Virus Strain Pre and Post-Injection With Either Sanofi Pasteur's CYD Dengue Vaccine or A Placebo Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT).	Day 0 (before each vaccination) and Day 28 post each vaccination
Percentage of Flavi Virus-Naive Participants With Antibody Titers of ≥10 1/Dil Against At Least 1, 2, 3, or 4 Serotypes With Parental Dengue Virus Strain Pre and Post-Injection With Either Sanofi Pasteur's CYD Dengue Vaccine or A Placebo Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT).	Day 0 (before each vaccination) and Day 28 post each vaccination
Summary of Geometric Mean Titers (GMTs) of Antibodies Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT).	Day 0 (before each vaccination) and Day 28 post-each vaccination
Summary of Geometric Mean Titers Ratios of Antibodies Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Geometric mean titer ratio is the geometric mean of individual post vaccination/pre vaccination titer of antibodies to each parental dengue virus serotype strain.	Day 0 (before each vaccination) and Day 28 post each vaccination
Summary of Geometric Mean Titers (GMTs) of Antibodies in Flavivirus-Immune Participants at Baseline Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-immune subjects at baseline are defined as those participants with ≥ 10 1/dil for at least one serotype with the parental dengue virus strain or for Yellow Fever titer.	Day 0 (before each vaccination) and Day 28 post each vaccination
Summary of Geometric Mean Titers Ratios of Antibodies in Flavivirus-Immune Participants at Baseline Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-immune subjects at baseline are defined as those participants with ≥ 10 1/dil for at least one serotype with the parental dengue virus strain or for Yellow Fever titer. Geometric mean titer ratio is the geometric mean of individual post vaccination/pre-vaccination titer of antibodies to each parental dengue virus serotype strain.	Day 0 (pre each vaccination) and Day 28 post each vaccination
Summary of Geometric Mean Titers (GMTs) of Antibodies in Flavivirus-Naïve Participants at Baseline Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-naïve participants are defined as those participants with < 10 1/dilutions for all serotypes with parental dengue virus strains and for Yellow Fever titer.	Day 0 (pre-each vaccination) and Day 28 post-each vaccination
Summary of Geometric Mean Titer Ratios of Antibodies in Flavivirus-Naive Participants at Baseline Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine	Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-naïve participants are defined as those participants with < 10 1/dil for all serotypes with parental dengue virus strains and for Yellow Fever titer. Geometric mean titer ratio is the geometric mean of individual post-vaccination/pre-vaccination titer of antibodies to each parental dengue virus serotype strain.	Day 0 (pre-each vaccination) and Day 28 post-each vaccination
Number of Participants Reporting a Solicited Injection-site or Systemic Reactions Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine	Solicited Injection-site reactions: Pain, Erythema, and Swelling. Solicited Systemic Reactions: Fever, (Temperature) Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited Injection-Site Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥ 5 cm. Grade 3 Solicited Systemic Reactions: Fever, ≥ 39˚C; Headache, Malaise, Myalgia, and Asthenia, Significant; prevents daily activity.	Day 0 up to Day 14 post-each vaccination

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Publications and helpful links

General Publications

• Villar LA, Rivera-Medina DM, Arredondo-Garcia JL, Boaz M, Starr-Spires L, Thakur M, Zambrano B, Miranda MC, Rivas E, Dayan GH. Safety and immunogenicity of a recombinant tetravalent dengue vaccine in 9-16 year olds: a randomized, controlled, phase II trial in Latin America. Pediatr Infect Dis J. 2013 Oct;32(10):1102-9. doi: 10.1097/INF.0b013e31829b8022.
• Coronel D, Garcia-Rivera EJ, Rivera DM, Arredondo-Garcia JL, Dietze R, Perroud AP, Cortes M, Bonaparte M, Wang H, Pagnon A, Jantet-Blaudez F, Penalosa LAR, Dayan G, Zambrano B, DiazGranados CA, Noriega F. Immune Response Persistence and Safety of a Booster Dose of the Tetravalent Dengue Vaccine in Adolescents and Adults Who Previously Completed the 3-dose Schedule 4-5 Years Earlier in Latin America: A Randomized Placebo-controlled Trial. Pediatr Infect Dis J. 2020 Oct;39(10):961-968. doi: 10.1097/INF.0000000000002830.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): March 1, 2012

Study Registration Dates

• First Submitted: October 9, 2009
• First Submitted That Met QC Criteria: October 9, 2009
• First Posted (Estimate): October 12, 2009

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; Dengue virus; Dengue fever; Dengue hemorrhagic fever; Sanofi pasteur's 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: CYD13; UTN: U1111-1111-5511

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