Study of CYD Dengue Vaccine in Healthy Children and Adolescents in South America

Phase 2

Completed

• Conditions: Dengue Hemorrhagic Fever; Dengue
• Interventions: Biological: NaCl 0.9%; Biological: Live, attenuated, recombinant dengue serotype 1 , 2, 3 , and 4 virus; Biological: Tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine adsorbed; Biological: Meningococcal A+C vaccine

• Registration Number: NCT01187433
• Lead Sponsor: Sanofi Pasteur, a Sanofi Company

Brief Summary

The purpose of this study is to generate immunogenicity and safety data in preparation for efficacy studies in Latin America.

Primary Objectives:

* To describe the immune response to dengue viruses before and after each vaccination with CYD dengue vaccine.

* To evaluate the safety of each vaccination with CYD dengue vaccine.

Detailed Description

Participants in the Dengue Vaccine Group will receive 3 vaccinations with CYD Dengue vaccine. Participants in the Control Group will receive placebo vaccinations for the first 2 vaccinations, followed by tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (ADACEL®) (in Venezuela) or Meningococcal A+C vaccine (in Brazil) as a way of providing therapeutic benefit to the participants in the control group.

Study Timeline

• Study Start: 2010-08
• Study First Submitted: 2010-08-20
• Study First Submitted QC: 2010-08-20
• Study First Posted: 2010-08-24
• Primary Completion: 2012-10
• Study Completion: 2012-12
• Disposition First Submitted: 2013-11-04
• Disposition First Submitted QC: 2013-11-04
• Disposition First Posted: 2013-11-27
• Results First Submitted: 2016-09-25
• Results First Submitted QC: 2016-09-25
• Results First Posted: 2016-11-11
• Status Verified: 2022-03
• Last Update Submitted: 2022-03-10
• Last Update Posted: 2022-03-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Group	NaCl 0.9%	Participants will receive a placebo, NaCl 0.9%.
Control Group	Tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine adsorbed	Participants will receive a placebo, NaCl 0.9%.
Control Group	Meningococcal A+C vaccine	Participants will receive a placebo, NaCl 0.9%.
Dengue Vaccine Group	Live, attenuated, recombinant dengue serotype 1 , 2, 3 , and 4 virus	Participants will receive Live, attenuated, recombinant dengue serotype 1 , 2, 3 , and 4 virus vaccine

Primary Outcome Measures

Name	Time	Method
Percentage of Flavivirus Immune Participants With Seropositivity Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Before and 28 days after each injection	Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer.
Percentage of Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Before and 28 days after each injection	Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
Geometric Mean Titer Ratios (GMTRs) Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Before and 28 days after each injection	Geometric mean titer ratios were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
Geometric Mean Titers (GMTs) Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Before and 28 days after each injection	Geometric mean titers were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
Percentage of Participants With Seropositivity Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Before and 28 days after each injection	Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
Percentage of Flavivirus Naïve Subjects With Seropositivity Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Before and 28 Days after each injection	Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus naïve subjects at baseline are defined as those subjects with \<10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer.
Percentage of Flavivirus Naïve Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Before and 28 days after each injection	Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus naïve subjects at baseline are defined as those subjects with \<10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer.
Geometric Mean Titer Ratios (GMTRs) of Flavivirus naïve Subjects Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Before and 28 days after each injection	Geometric mean titers were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus naïve subjects at baseline are defined as those subjects with \<10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer.
Percentage of Flavivirus Immune Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Before and 28 days after each injection	Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer.
Geometric Mean Titers (GMTs) of Flavivirus Immune Subjects Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo	Before and 28 days after each injection	Geometric mean titers were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer.
Percentage of Participants Reporting Solicited Injection-Site and Systemic Reactions Following Any and Each Vaccination With Either CYD Dengue Vaccine or a Placebo	Day 0 up to Day 14 post each vaccination	Injection-site reactions: Pain, Erythema, and Swelling. Systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Injection-site reactions (9 to 11 years): Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥5 cm. Grade 3 Injection site reactions (≥12 years): Pain, Significant; prevents daily activity; Erythema and Swelling, \>10 cm. Grade 3 Systemic reactions: Fever, ≥39˚C; Headache, Malaise, Myalgia, and Asthenia, Significant; prevents daily activity.