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

Primary Purpose

Dengue, Dengue Hemorrhagic Fever

Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Live, attenuated, recombinant dengue serotype 1 , 2, 3 , and 4 virus
NaCl 0.9%
Tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine adsorbed
Meningococcal A+C vaccine
Sponsored by
Sanofi Pasteur, a Sanofi Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Dengue focused on measuring Dengue, Dengue hemorrhagic fever, CYD Dengue Vaccines

Eligibility Criteria

9 Years - 16 Years (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria :

  • Aged 9 to 16 years on the day of inclusion
  • Participant in good health, based on medical history and physical examination
  • Provision of assent form/informed consent form signed by the participant and by the parent(s) or another legally acceptable representative
  • Participant and parent(s)/legally acceptable representative(s) able to attend all scheduled visits and to comply with all trial procedures
  • For a female participant 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 participant 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 participant'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
  • Participant deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized without his/her consent
  • Febrile illness (temperature ≥ 38.0 ºC) 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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Dengue Vaccine Group

Control Group

Arm Description

Participants will receive Live, attenuated, recombinant dengue serotype 1 , 2, 3 , and 4 virus vaccine

Participants will receive a placebo, NaCl 0.9%.

Outcomes

Primary Outcome Measures

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
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 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
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 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
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 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
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 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
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 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
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) Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo
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
Geometric mean titers were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
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
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.
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
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 Participants Reporting Solicited Injection-Site and Systemic Reactions Following Any and Each Vaccination With Either CYD Dengue Vaccine or a Placebo
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.

Secondary Outcome Measures

Full Information

First Posted
August 20, 2010
Last Updated
March 10, 2022
Sponsor
Sanofi Pasteur, a Sanofi Company
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1. Study Identification

Unique Protocol Identification Number
NCT01187433
Brief Title
Study of CYD Dengue Vaccine in Healthy Children and Adolescents in South America
Official Title
Immunogenicity and Safety of CYD Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in South America
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
August 2010 (undefined)
Primary Completion Date
October 2012 (Actual)
Study Completion Date
December 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi Pasteur, a Sanofi Company

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue, Dengue Hemorrhagic Fever
Keywords
Dengue, Dengue hemorrhagic fever, CYD Dengue Vaccines

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dengue Vaccine Group
Arm Type
Experimental
Arm Description
Participants will receive Live, attenuated, recombinant dengue serotype 1 , 2, 3 , and 4 virus vaccine
Arm Title
Control Group
Arm Type
Placebo Comparator
Arm Description
Participants will receive a placebo, NaCl 0.9%.
Intervention Type
Biological
Intervention Name(s)
Live, attenuated, recombinant dengue serotype 1 , 2, 3 , and 4 virus
Other Intervention Name(s)
CYD Dengue Vaccine
Intervention Description
0.5 mL, Subcutaneous (SC)
Intervention Type
Biological
Intervention Name(s)
NaCl 0.9%
Intervention Description
0.5 mL, Subcutaneous
Intervention Type
Biological
Intervention Name(s)
Tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine adsorbed
Other Intervention Name(s)
ADACEL®
Intervention Description
0.5 mL, Intramuscular
Intervention Type
Biological
Intervention Name(s)
Meningococcal A+C vaccine
Intervention Description
0.5 mL, Intramuscular
Primary Outcome Measure Information:
Title
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
Description
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).
Time Frame
Before and 28 days after each injection
Title
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
Description
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.
Time Frame
Before and 28 days after each injection
Title
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
Description
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.
Time Frame
Before and 28 Days after each injection
Title
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
Description
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).
Time Frame
Before and 28 days after each injection
Title
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
Description
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.
Time Frame
Before and 28 days after each injection
Title
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
Description
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.
Time Frame
Before and 28 days after each injection
Title
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
Description
Geometric mean titer ratios were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
Time Frame
Before and 28 days after each injection
Title
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
Description
Geometric mean titers were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT).
Time Frame
Before and 28 days after each injection
Title
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
Description
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.
Time Frame
Before and 28 days after each injection
Title
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
Description
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.
Time Frame
Before and 28 days after each injection
Title
Percentage of Participants Reporting Solicited Injection-Site and Systemic Reactions Following Any and Each Vaccination With Either CYD Dengue Vaccine or a Placebo
Description
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.
Time Frame
Day 0 up to Day 14 post each vaccination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
9 Years
Maximum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria : Aged 9 to 16 years on the day of inclusion Participant in good health, based on medical history and physical examination Provision of assent form/informed consent form signed by the participant and by the parent(s) or another legally acceptable representative Participant and parent(s)/legally acceptable representative(s) able to attend all scheduled visits and to comply with all trial procedures For a female participant 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 participant 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 participant'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 Participant deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized without his/her consent Febrile illness (temperature ≥ 38.0 ºC) 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sanofi Pasteur Inc.
Official's Role
Study Director
Facility Information:
City
Vitória
ZIP/Postal Code
ES, 29040-091
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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
Citations:
PubMed Identifier
24189367
Citation
Dayan GH, Garbes P, Noriega F, Izoton de Sadovsky AD, Rodrigues PM, Giuberti C, Dietze R. Immunogenicity and safety of a recombinant tetravalent dengue vaccine in children and adolescents ages 9-16 years in Brazil. Am J Trop Med Hyg. 2013 Dec;89(6):1058-1065. doi: 10.4269/ajtmh.13-0304. Epub 2013 Nov 4.
Results Reference
result
PubMed Identifier
32932330
Citation
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.
Results Reference
derived
Links:
URL
http://www.sanofipasteur.com
Description
Related Info

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

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