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Immunogenicity and Safety of Three Formulations of Dengue Vaccines in Healthy Adults Aged 18 to 45 Years in the US

Primary Purpose

Dengue Fever, Dengue Hemorrhagic Fever, Dengue Virus

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Tetravalent CYD Dengue Vaccine , 5555 formulation
Tetravalent CYD Dengue Vaccine , 5553 formulation
Tetravalent CYD Dengue Vaccine, 4444 formulation
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Dengue Fever focused on measuring Dengue fever, Dengue hemorrhagic fever, Dengue virus

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy, as determined by medical history, clinical examination, and biological safety parameters.
  • Aged 18 to 45 years on the day of inclusion.
  • Provision of informed consent signed by the participant or another legally acceptable representative.
  • For a woman of child-bearing potential, use of an effective method of contraception or abstinence for at least 4 weeks prior to the first vaccination, and until at least 4 weeks after the last study vaccination.
  • Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

  • Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.
  • For a woman of child-bearing potential, known or suspected pregnancy or positive serum/urine pregnancy test.
  • Breast-feeding woman.
  • Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.
  • 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 (at least 2 weeks within the previous 3 months) systemic corticosteroids therapy (at a dose of at least 10 mg). Topical steroids were allowed.
  • Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccine 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 or past 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 past 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 each of the trial vaccinations.
  • Human Immunodeficiency Virus (HIV), hepatitis B surface antigen, or hepatitis C virus seropositivity in blood sample taken at Screening.
  • Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
  • Clinically significant laboratory test abnormalities (as determined by the investigator) in blood sample taken at Screening.
  • Previous residence in, travel or planned travel of more than 2 weeks during the study period to areas with high dengue infection endemicity.
  • Reported history of flavivirus infection as reported by the participant.
  • Previous vaccination against flavivirus diseases (including Japanese encephalitis, tick-borne encephalitis, and yellow fever).
  • Flavivirus vaccination planned during the trial period.

Sites / Locations

  • Investigational Site 004
  • Investigational Site 002
  • Investigational Site 005
  • Investigational Site 001
  • Investigational Site 003

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

CYD Dengue Vaccine 5555 Formulation

CYD Dengue Vaccine 5553 Formulation

CYD Dengue Vaccine 4444 Formulation

Arm Description

Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months.

Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months.

Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months.

Outcomes

Primary Outcome Measures

Percentage of Participants With Antibody Titers of >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain: CYD Vaccine 5555 and 5553 Formulation
Percentage of participants with antibody titers >= 10 (1/dil) against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by dengue plaque reduction neutralization test (PRNT).

Secondary Outcome Measures

Percentage of Participants With Antibody Titers of >=10 1/Dil Against Each Dengue Virus Serotype Strain
Percentage of participants with antibody titers >= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT.
Percentage of Participants With Antibody Titers >=10 1/Dil Against At Least Any 1, 2, 3 or All 4 Dengue Virus Serotypes
Percentage of participants with antibody titers >= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT. In this outcome measure, participants with antibody titers >= 10 1/dil against any 1 of the 4 serotypes or any 2 of the 4 serotypes or any 3 of the 4 serotypes or with all 4 serotypes were reported.
Geometric Means of Titers of Antibodies Against Each Dengue Virus Serotype Strain
Geometric mean titers against each dengue virus serotype (1, 2, 3 and 4) strain was measured by PRNT.
Number of Participants With Solicited Injection Site Reactions After Any Vaccination
Solicited injection site reactions: Pain, Erythema, and Swelling. Pain: Grade 1: Easily tolerated, Grade 2: Sufficiently discomforting to interfere with normal behavior or activities, Grade 3: Incapacitating, unable to perform usual activities. Erythema:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >=5 cm. Swelling:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >=5 cm.
Number of Participants With Solicited Systemic Reactions After Any Vaccination
Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever: - Grade1: >=37.5°C to <=38.0°C (>=99.5°F to <=100.4°F), Grade 2: >38.0°C to <=39.0°C (>100.4°F to <= 102.2°F), Grade 3: >39.0°C (>102.2°F). Headache, malaise, myalgia and asthenia: Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities.
Number of Participants With Vaccine Viremia
Vaccine viremia (level of vaccine virus in blood samples taken from participants) was measured by an assay yellow fever reverse transcriptase polymerase chain reaction which allowed the detection of vaccine viremia of any serotype (1, 2, 3 and 4).

Full Information

First Posted
February 6, 2008
Last Updated
May 21, 2019
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT00617344
Brief Title
Immunogenicity and Safety of Three Formulations of Dengue Vaccines in Healthy Adults Aged 18 to 45 Years in the US
Official Title
Immunogenicity and Safety of Three Tetravalent Formulations of Dengue Vaccine Candidates in Healthy Adults Aged 18 to 45 Years in the US
Study Type
Interventional

2. Study Status

Record Verification Date
May 2019
Overall Recruitment Status
Completed
Study Start Date
April 17, 2008 (Actual)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
February 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study used 3 different formulations of tetravalent CYD dengue vaccine. The primary objective of the study was to evaluate the neutralizing antibody response after 2 doses of two different formulations of tetravalent dengue vaccine administered at Month 0 and Month 6. The secondary objectives were: To evaluate the safety of the 3 formulations of tetravalent CYD dengue vaccine. To describe the neutralizing antibody responses to each of the 3 vaccine formulations. To describe vaccine viremia after the first and second dose of each of the 3 vaccine formulations in a subset of participants.
Detailed Description
All participants provided blood samples for immunogenicity assessments, while vaccine viremia was assessed in a subset of participants in each group. Safety was assessed in all participants as follows: solicited adverse event (AE) prelisted in the diary card were collected for 7 days after vaccination for solicited injection site reactions and 14 days for solicited systemic reactions , unsolicited AEs were collected for 28 days after vaccination, and serious adverse event (SAE) information collected throughout the study up to 6 months after vaccination.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
260 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CYD Dengue Vaccine 5555 Formulation
Arm Type
Experimental
Arm Description
Participants received 3 doses of CYD dengue vaccine (5555 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months.
Arm Title
CYD Dengue Vaccine 5553 Formulation
Arm Type
Experimental
Arm Description
Participants received 3 doses of CYD dengue vaccine (5553 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months.
Arm Title
CYD Dengue Vaccine 4444 Formulation
Arm Type
Experimental
Arm Description
Participants received 3 doses of CYD dengue vaccine (4444 formulation); one each at 0 (vaccination 1), 6 (vaccination 2), and 12 (vaccination 3) months.
Intervention Type
Biological
Intervention Name(s)
Tetravalent CYD Dengue Vaccine , 5555 formulation
Intervention Description
A 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively.
Intervention Type
Biological
Intervention Name(s)
Tetravalent CYD Dengue Vaccine , 5553 formulation
Intervention Description
A 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively
Intervention Type
Biological
Intervention Name(s)
Tetravalent CYD Dengue Vaccine, 4444 formulation
Intervention Description
A 0.5 mL dose, Subcutaneous at 0, 6, and 12 months, respectively
Primary Outcome Measure Information:
Title
Percentage of Participants With Antibody Titers of >= 10 1/Dilution (1/Dil) Against Each Dengue Virus Serotype Strain: CYD Vaccine 5555 and 5553 Formulation
Description
Percentage of participants with antibody titers >= 10 (1/dil) against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by dengue plaque reduction neutralization test (PRNT).
Time Frame
Pre-injection 1 (Day 0), 30 days post-injection 2 (Month 7)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Antibody Titers of >=10 1/Dil Against Each Dengue Virus Serotype Strain
Description
Percentage of participants with antibody titers >= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT.
Time Frame
Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
Title
Percentage of Participants With Antibody Titers >=10 1/Dil Against At Least Any 1, 2, 3 or All 4 Dengue Virus Serotypes
Description
Percentage of participants with antibody titers >= 10 1/dil against each serotypes (1, 2, 3 and 4) of the dengue virus strains was assessed by PRNT. In this outcome measure, participants with antibody titers >= 10 1/dil against any 1 of the 4 serotypes or any 2 of the 4 serotypes or any 3 of the 4 serotypes or with all 4 serotypes were reported.
Time Frame
Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
Title
Geometric Means of Titers of Antibodies Against Each Dengue Virus Serotype Strain
Description
Geometric mean titers against each dengue virus serotype (1, 2, 3 and 4) strain was measured by PRNT.
Time Frame
Pre-injection 1 (Day 0), 30 days post-injection 1(Month 1), injection 2 (Month 7) and injection 3 (Month 13)
Title
Number of Participants With Solicited Injection Site Reactions After Any Vaccination
Description
Solicited injection site reactions: Pain, Erythema, and Swelling. Pain: Grade 1: Easily tolerated, Grade 2: Sufficiently discomforting to interfere with normal behavior or activities, Grade 3: Incapacitating, unable to perform usual activities. Erythema:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >=5 cm. Swelling:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >=5 cm.
Time Frame
7 days after any injection 1, 2 or 3
Title
Number of Participants With Solicited Systemic Reactions After Any Vaccination
Description
Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever: - Grade1: >=37.5°C to <=38.0°C (>=99.5°F to <=100.4°F), Grade 2: >38.0°C to <=39.0°C (>100.4°F to <= 102.2°F), Grade 3: >39.0°C (>102.2°F). Headache, malaise, myalgia and asthenia: Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities.
Time Frame
14 days after any injection 1, 2 or 3
Title
Number of Participants With Vaccine Viremia
Description
Vaccine viremia (level of vaccine virus in blood samples taken from participants) was measured by an assay yellow fever reverse transcriptase polymerase chain reaction which allowed the detection of vaccine viremia of any serotype (1, 2, 3 and 4).
Time Frame
7 days post-injection 1 and 2, 14 days post-injection 1 and 2

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy, as determined by medical history, clinical examination, and biological safety parameters. Aged 18 to 45 years on the day of inclusion. Provision of informed consent signed by the participant or another legally acceptable representative. For a woman of child-bearing potential, use of an effective method of contraception or abstinence for at least 4 weeks prior to the first vaccination, and until at least 4 weeks after the last study vaccination. Able to attend all scheduled visits and to comply with all trial procedures. Exclusion Criteria: Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia. For a woman of child-bearing potential, known or suspected pregnancy or positive serum/urine pregnancy test. Breast-feeding woman. Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination. 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 (at least 2 weeks within the previous 3 months) systemic corticosteroids therapy (at a dose of at least 10 mg). Topical steroids were allowed. Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccine 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 or past 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 past 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 each of the trial vaccinations. Human Immunodeficiency Virus (HIV), hepatitis B surface antigen, or hepatitis C virus seropositivity in blood sample taken at Screening. Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent. Clinically significant laboratory test abnormalities (as determined by the investigator) in blood sample taken at Screening. Previous residence in, travel or planned travel of more than 2 weeks during the study period to areas with high dengue infection endemicity. Reported history of flavivirus infection as reported by the participant. Previous vaccination against flavivirus diseases (including Japanese encephalitis, tick-borne encephalitis, and yellow fever). Flavivirus vaccination planned during the trial period.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi Pasteur, a Sanofi Company
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site 004
City
Hoover
State/Province
Alabama
ZIP/Postal Code
35126
Country
United States
Facility Name
Investigational Site 002
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Investigational Site 005
City
Vallejo
State/Province
California
ZIP/Postal Code
94589
Country
United States
Facility Name
Investigational Site 001
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70119
Country
United States
Facility Name
Investigational Site 003
City
Springfield
State/Province
Missouri
ZIP/Postal Code
65802
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
24021313
Citation
Dayan GH, Thakur M, Boaz M, Johnson C. Safety and immunogenicity of three tetravalent dengue vaccine formulations in healthy adults in the USA. Vaccine. 2013 Oct 17;31(44):5047-54. doi: 10.1016/j.vaccine.2013.08.088. Epub 2013 Sep 7.
Results Reference
result

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Immunogenicity and Safety of Three Formulations of Dengue Vaccines in Healthy Adults Aged 18 to 45 Years in the US

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