Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier:
NCT00993447
First received: October 9, 2009
Last updated: October 4, 2016
Last verified: October 2016
  Purpose

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.

Condition Intervention Phase
Dengue
Dengue Hemorrhagic Fever
Dengue Virus
Dengue Fever
Biological: CYD Dengue Vaccine
Biological: Tetanus Toxoid Reduced Diphtheria Toxoid Acellular Pertussis
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Immunogenicity and Safety of Sanofi Pasteur's CYD Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 [ Time Frame: Day 0 (pre-each vaccination) and Day 28 post-each vaccination ] [ Designated as safety issue: No ]
    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).

  • 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 [ Time Frame: Day 0 (pre-each vaccination) and Day 28 post-each vaccination ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 0 (pre-each vaccination) and Day 28 post-each vaccination ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 0 (before each vaccination) and Day 28 post each vaccination ] [ Designated as safety issue: No ]
    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).

  • 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 [ Time Frame: Day 0 (before each vaccination) and Day 28 post each vaccination ] [ Designated as safety issue: No ]
    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).

  • 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 [ Time Frame: Day 0 (before each vaccination) and Day 28 post each vaccination ] [ Designated as safety issue: No ]
    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).

  • 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 [ Time Frame: Day 0 (before each vaccination) and Day 28 post-each vaccination ] [ Designated as safety issue: No ]
    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).

  • 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 [ Time Frame: Day 0 (before each vaccination) and Day 28 post each vaccination ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 0 (before each vaccination) and Day 28 post each vaccination ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 0 (pre each vaccination) and Day 28 post each vaccination ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 0 (pre-each vaccination) and Day 28 post-each vaccination ] [ Designated as safety issue: No ]
    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.

  • 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 [ Time Frame: Day 0 (pre-each vaccination) and Day 28 post-each vaccination ] [ Designated as safety issue: No ]

    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.


  • Number of Participants Reporting a Solicited Injection-site or Systemic Reactions Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine [ Time Frame: Day 0 up to Day 14 post-each vaccination ] [ Designated as safety issue: No ]
    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.


Enrollment: 600
Study Start Date: October 2009
Study Completion Date: March 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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:
  • ADACEL®
  • NaCl

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.
  Eligibility

Ages Eligible for Study:   9 Years to 16 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00993447

Locations
Colombia
Bucaramanga, Colombia
Honduras
Tegucigalpa, Honduras
Mexico
Cuernavaca, Mexico
Puerto Rico
San Juan, Puerto Rico
Sponsors and Collaborators
Sanofi Pasteur, a Sanofi Company
Investigators
Study Director: Medical Director Sanofi Pasteur Inc.
  More Information

Additional Information:
Publications:
Responsible Party: Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier: NCT00993447     History of Changes
Other Study ID Numbers: CYD13  UTN: U1111-1111-5511 
Study First Received: October 9, 2009
Results First Received: October 4, 2016
Last Updated: October 4, 2016
Health Authority: United States: Food and Drug Administration
Colombia: INVIMA Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Honduras: Secretaria de Salud, Subsecretaria de Riesgos Poblacionales
Mexico: Ministry of Health
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Individual participant data (IPD) and supporting clinical documents are available for request at www.clinicalstudydatarequest.com. While making information available we continue to protect the privacy of the participants in our clinical trials and to remove commercially confidential information (CCI). Details on Data Sharing criteria and process for requesting access can be found at this web address: Clinicalstudydatarequest.com/Sanofi.

Keywords provided by Sanofi:
Dengue
Dengue hemorrhagic fever
Dengue virus
Dengue fever
Sanofi pasteur's CYD Dengue vaccine

Additional relevant MeSH terms:
Fever
Dengue
Hemorrhagic Fevers, Viral
Severe Dengue
Body Temperature Changes
Signs and Symptoms
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 02, 2016