Clinical trial NCT01943825: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dengue
Dengue Fever
Dengue Hemorrhagic Fever
Keywords: Dengue
Dengue fever
CYD dengue vaccine
IXIARO JE vaccine
Flavivirus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: United States Department of Defense
First posted: 2013-09-17
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Geometric Means Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype Strains
timeFrame: Pre-injection 1, 2 and 3; 28 days post-injection 1, 2 and 3; and 6 months post-injection 3
measure: Number of Participants With Antibody Titers Greater Than or Equal to (>=)10 (1/Dilution) Against Each Dengue Virus Serotype Strains
timeFrame: Pre-injection 1, 2 and 3; 28 days post-injection 1, 2 and 3; and 6 months post-injection 3
Secondary outcomes:
measure: Geometric Means Titers of Antibodies Against Each Dengue Virus Serotype Strains in Participants Who Received Japanese Encephalitis Vaccine - Groups 3 and 4
timeFrame: Pre-injection 1, 2 and 3, and 28 days post-injection 1, 2 and 3
measure: Geometric Means Titers of Antibodies Against Each Dengue Virus Serotype Strains
timeFrame: 6 months and 12 months post-injection 3
measure: Number of Participants With Detectable Non Serotype-Specific Vaccine Viremia
timeFrame: 3, 5, 7 and 14 days post-injection 1, 2 and 3
measure: Number of Participants With Detectable Serotype-Specific Vaccine Viremia
timeFrame: 3, 5, 7 and 14 days post-injection 1; 3 and 14 days post-injection 2 and 7 days post-injection 3
measure: Geometric Means Titers of Antibodies Against Japanese Encephalitis - Groups 3 and 4
timeFrame: Pre-injection 1, and 28 days post-injection 1, 2 and 3
measure: Number of Participants With Solicited Injection Site Reactions
timeFrame: Within 7 days after any CYD dengue vaccine and/or JE vaccine
measure: Number of Participants With Solicited Systemic Reactions
timeFrame: Within 14 days after any CYD dengue vaccine and/or JE vaccine
Other outcomes:
Locations:
city: Syracuse
country: United States
state: New York
Study officials:
affiliation: Sanofi Pasteur SA
name: Medical Director
role: STUDY_DIRECTOR
References: