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Immunologic Mechanisms of Immune Interference and/or Cross-Neutralizing Immunity After CYD Tetravalent Dengue Vaccine

Primary Purpose

Dengue, Dengue Fever, Dengue Hemorrhagic Fever

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
CYD Dengue Vaccine
CYD Dengue Vaccine
Japanese Encephalitis Vaccine
Japanese Encephalitis 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 fever, CYD dengue vaccine, IXIARO JE vaccine, Flavivirus

Eligibility Criteria

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

Inclusion Criteria:

  • Aged greater than or equal to (>=)18 to less than or equal to (<=) 45 years on the day of inclusion.
  • Informed consent form had been signed and dated.
  • Able to attend all scheduled visits and complied with all trial procedures.
  • Participant was in good health, based on medical history and physical examination.

Exclusion Criteria:

  • Participant was pregnant, or lactating, or of childbearing potential (were considered of non-childbearing potential, a female had to be post- menopausal for at least 1 year, surgically sterile, or used an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination).
  • Participation in the 4 weeks preceding the first trial vaccination, or planned participation during the present trial period, in another clinical trial investigating a vaccine, drug, medical device, or medical procedure.
  • Receipt or planned receipt of any vaccine, outside the study protocol in the 4 weeks preceded or followed trial vaccinations. (If influenza activity warranted vaccination of healthy young adults, influenza vaccination was encouraged and did not lead to study exclusion).
  • Any history of FV vaccination, or planned FV vaccination during the trial period.
  • Previous residence (greater than [>]12 months) in, or travel in the last 30 days to dengue endemic regions.
  • Receipt of immune globulins, blood or blood-derived products in the 3 months prior to first vaccination or planned use during the study period.
  • Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceded 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
  • Known systemic hypersensitivity to any of the vaccine components (including protamine sulfate), or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances, including dry natural latex.
  • Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.
  • Excessive alcohol consumption or drug addiction.
  • Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with trial conduct or completion.
  • Identified as an employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employee or the Investigator.
  • Temporary Exclusion Criteria: Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature >= 38.0 degree Celsius [>= 100.4 degree fahrenheit]). A prospective participant was not included in the study until the condition had resolved or the febrile event had subsided. If the delay for the febrile illness exceeded the window between screening and vaccination, or if deemed necessary by the Investigator, a prospective participant might be re-screened once the fever had resolved.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

CYD Dengue Vaccine: Group 1

CYD Dengue Vaccine: Group 2

CYD Dengue and JE Vaccine: Group 3

CYD Dengue and JE Vaccine: Group 4

Arm Description

Participants received 3 doses of CYD dengue vaccine, one each at 0, 2 and 6 months, respectively.

Participants received 3 doses of CYD dengue vaccine, one each at 0, 6 and 12 months, respectively.

Participants received 3 doses of CYD dengue vaccine, one each at 0, 2 and 6 months, and 2 doses of JE (IXIARO) vaccine at 0 and 1 months, respectively.

Participants received 2 doses of JE (IXIARO) vaccine at 0 and 1 months; and 3 doses of CYD dengue vaccine at 7, 9 and 13 months, respectively.

Outcomes

Primary Outcome Measures

Geometric Means Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype Strains
GMTs of antibodies against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by plaque reduction neutralization test (PRNT). The lower limit of quantitation (LLOQ) of the assay was a titer of 10 (1/dilution).
Number of Participants With Antibody Titers Greater Than or Equal to (>=)10 (1/Dilution) Against Each Dengue Virus Serotype Strains
Antibody titers against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by PRNT.

Secondary Outcome Measures

Geometric Means Titers of Antibodies Against Each Dengue Virus Serotype Strains in Participants Who Received Japanese Encephalitis Vaccine - Groups 3 and 4
GMTs of antibodies against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by PRNT. The LLOQ of the assay was a titer of 10 (1/dilution).
Geometric Means Titers of Antibodies Against Each Dengue Virus Serotype Strains
GMTs of antibodies against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by PRNT.
Number of Participants With Detectable Non Serotype-Specific Vaccine Viremia
Viremia was determined by reverse transcriptase (RT) polymerase chain reaction (PCR) using primer/probes specific to a non serotype-specific part of the dengue vaccine.
Number of Participants With Detectable Serotype-Specific Vaccine Viremia
Viremia was determined by RT PCR using primer/probes specific to each dengue vaccine serotypes.
Geometric Means Titers of Antibodies Against Japanese Encephalitis - Groups 3 and 4
GMTs of antibodies against JE were measured by JE micro neutralization assay. The LLOQ of the assay was a titer of 10 (1/dilution).
Number of Participants With Solicited Injection Site Reactions
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) pre-listed (i.e., solicited) in the electronic case report form (eCRF) and considered as related to vaccination. Solicited injection site reactions: pain, erythema, and swelling.
Number of Participants With Solicited Systemic Reactions
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) pre-listed (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited systemic reactions: fever, headache, malaise, myalgia, and asthenia.

Full Information

First Posted
September 12, 2013
Last Updated
March 15, 2022
Sponsor
Sanofi Pasteur, a Sanofi Company
Collaborators
United States Department of Defense
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1. Study Identification

Unique Protocol Identification Number
NCT01943825
Brief Title
Immunologic Mechanisms of Immune Interference and/or Cross-Neutralizing Immunity After CYD Tetravalent Dengue Vaccine
Official Title
Exploration of Immunologic Mechanisms of Immune Interference and/or Cross-Neutralizing Immunity Following Various Administration Schedules With CYD Tetravalent Dengue Vaccine
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
November 5, 2013 (Actual)
Primary Completion Date
November 25, 2015 (Actual)
Study Completion Date
November 25, 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi Pasteur, a Sanofi Company
Collaborators
United States Department of Defense

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The aim of the study was to evaluate a compressed dosing schedule and the immunologic effects of co-administration of a CYD dengue vaccine with a licensed flavivirus (FV) with Japanese encephalitis (JE) vaccine. Primary Objectives: To describe and compare the humoral immune response to each of the 4 parental dengue virus serotypes at baseline and 28 days after each CYD dengue vaccine dose. To describe the persistence of the humoral immune response to each of the 4 parental dengue virus serotypes 6 after CYD dengue vaccine Dose 3, irrespective of whether or not JE vaccine had been previously administered. Secondary Objectives: To describe the safety profile after each injection of CYD dengue vaccine. To describe the humoral immune response to each of the 4 parental dengue virus serotypes at baseline and 28 days after each CYD dengue vaccine dose when administered with or after JE virus vaccine in Groups 3 and 4. To describe the persistence of the humoral immune response to each of the 4 parental dengue virus serotypes at 6 months post-dose 3 in all four groups and at 12 months post-dose 3 in Groups 1 and 3 with the compressed schedule. To determine the level of viremia on Day (D)0, D3, D5, D7 and D14 following each CYD vaccine dose administered in Groups 1-4. To describe the JE humoral immune response at baseline and 28 days after each injection of CYD dengue vaccine in Groups 3 and 4.
Detailed Description
Study participants were randomly assigned to one of the four groups to receive assigned study vaccine and were evaluated for neutralizing antibody titers; markers of cell-mediated immunity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue, Dengue Fever, Dengue Hemorrhagic Fever
Keywords
Dengue, Dengue fever, CYD dengue vaccine, IXIARO JE vaccine, Flavivirus

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CYD Dengue Vaccine: Group 1
Arm Type
Experimental
Arm Description
Participants received 3 doses of CYD dengue vaccine, one each at 0, 2 and 6 months, respectively.
Arm Title
CYD Dengue Vaccine: Group 2
Arm Type
Experimental
Arm Description
Participants received 3 doses of CYD dengue vaccine, one each at 0, 6 and 12 months, respectively.
Arm Title
CYD Dengue and JE Vaccine: Group 3
Arm Type
Experimental
Arm Description
Participants received 3 doses of CYD dengue vaccine, one each at 0, 2 and 6 months, and 2 doses of JE (IXIARO) vaccine at 0 and 1 months, respectively.
Arm Title
CYD Dengue and JE Vaccine: Group 4
Arm Type
Experimental
Arm Description
Participants received 2 doses of JE (IXIARO) vaccine at 0 and 1 months; and 3 doses of CYD dengue vaccine at 7, 9 and 13 months, respectively.
Intervention Type
Biological
Intervention Name(s)
CYD Dengue Vaccine
Intervention Description
0.5 mL, Subcutaneous
Intervention Type
Biological
Intervention Name(s)
CYD Dengue Vaccine
Intervention Description
0.5 mL, Subcutaneous
Intervention Type
Biological
Intervention Name(s)
Japanese Encephalitis Vaccine
Other Intervention Name(s)
IXIARO Japanese Encephalitis Vaccine
Intervention Description
0.5 mL, Intramuscular
Intervention Type
Biological
Intervention Name(s)
Japanese Encephalitis Vaccine
Other Intervention Name(s)
IXIARO Japanese Encephalitis Vaccine
Intervention Description
0.5 mL, Intramuscular
Primary Outcome Measure Information:
Title
Geometric Means Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype Strains
Description
GMTs of antibodies against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by plaque reduction neutralization test (PRNT). The lower limit of quantitation (LLOQ) of the assay was a titer of 10 (1/dilution).
Time Frame
Pre-injection 1, 2 and 3; 28 days post-injection 1, 2 and 3; and 6 months post-injection 3
Title
Number of Participants With Antibody Titers Greater Than or Equal to (>=)10 (1/Dilution) Against Each Dengue Virus Serotype Strains
Description
Antibody titers against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by PRNT.
Time Frame
Pre-injection 1, 2 and 3; 28 days post-injection 1, 2 and 3; and 6 months post-injection 3
Secondary Outcome Measure Information:
Title
Geometric Means Titers of Antibodies Against Each Dengue Virus Serotype Strains in Participants Who Received Japanese Encephalitis Vaccine - Groups 3 and 4
Description
GMTs of antibodies against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by PRNT. The LLOQ of the assay was a titer of 10 (1/dilution).
Time Frame
Pre-injection 1, 2 and 3, and 28 days post-injection 1, 2 and 3
Title
Geometric Means Titers of Antibodies Against Each Dengue Virus Serotype Strains
Description
GMTs of antibodies against each dengue virus serotype (parental strains 1, 2, 3 and 4) were measured by PRNT.
Time Frame
6 months and 12 months post-injection 3
Title
Number of Participants With Detectable Non Serotype-Specific Vaccine Viremia
Description
Viremia was determined by reverse transcriptase (RT) polymerase chain reaction (PCR) using primer/probes specific to a non serotype-specific part of the dengue vaccine.
Time Frame
3, 5, 7 and 14 days post-injection 1, 2 and 3
Title
Number of Participants With Detectable Serotype-Specific Vaccine Viremia
Description
Viremia was determined by RT PCR using primer/probes specific to each dengue vaccine serotypes.
Time Frame
3, 5, 7 and 14 days post-injection 1; 3 and 14 days post-injection 2 and 7 days post-injection 3
Title
Geometric Means Titers of Antibodies Against Japanese Encephalitis - Groups 3 and 4
Description
GMTs of antibodies against JE were measured by JE micro neutralization assay. The LLOQ of the assay was a titer of 10 (1/dilution).
Time Frame
Pre-injection 1, and 28 days post-injection 1, 2 and 3
Title
Number of Participants With Solicited Injection Site Reactions
Description
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) pre-listed (i.e., solicited) in the electronic case report form (eCRF) and considered as related to vaccination. Solicited injection site reactions: pain, erythema, and swelling.
Time Frame
Within 7 days after any CYD dengue vaccine and/or JE vaccine
Title
Number of Participants With Solicited Systemic Reactions
Description
A solicited reaction was defined as an adverse reaction observed and reported under the conditions (symptom and onset) pre-listed (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited systemic reactions: fever, headache, malaise, myalgia, and asthenia.
Time Frame
Within 14 days after any CYD dengue vaccine and/or JE vaccine

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: Aged greater than or equal to (>=)18 to less than or equal to (<=) 45 years on the day of inclusion. Informed consent form had been signed and dated. Able to attend all scheduled visits and complied with all trial procedures. Participant was in good health, based on medical history and physical examination. Exclusion Criteria: Participant was pregnant, or lactating, or of childbearing potential (were considered of non-childbearing potential, a female had to be post- menopausal for at least 1 year, surgically sterile, or used an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination and until at least 4 weeks after the last vaccination). Participation in the 4 weeks preceding the first trial vaccination, or planned participation during the present trial period, in another clinical trial investigating a vaccine, drug, medical device, or medical procedure. Receipt or planned receipt of any vaccine, outside the study protocol in the 4 weeks preceded or followed trial vaccinations. (If influenza activity warranted vaccination of healthy young adults, influenza vaccination was encouraged and did not lead to study exclusion). Any history of FV vaccination, or planned FV vaccination during the trial period. Previous residence (greater than [>]12 months) in, or travel in the last 30 days to dengue endemic regions. Receipt of immune globulins, blood or blood-derived products in the 3 months prior to first vaccination or planned use during the study period. Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceded 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) Known systemic hypersensitivity to any of the vaccine components (including protamine sulfate), or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances, including dry natural latex. Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily. Excessive alcohol consumption or drug addiction. Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with trial conduct or completion. Identified as an employee of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife and their children, adopted or natural) of the employee or the Investigator. Temporary Exclusion Criteria: Moderate or severe acute illness/infection (according to Investigator judgment) on the day of vaccination or febrile illness (temperature >= 38.0 degree Celsius [>= 100.4 degree fahrenheit]). A prospective participant was not included in the study until the condition had resolved or the febrile event had subsided. If the delay for the febrile illness exceeded the window between screening and vaccination, or if deemed necessary by the Investigator, a prospective participant might be re-screened once the fever had resolved.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Sanofi Pasteur SA
Official's Role
Study Director
Facility Information:
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States

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

Learn more about this trial

Immunologic Mechanisms of Immune Interference and/or Cross-Neutralizing Immunity After CYD Tetravalent Dengue Vaccine

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