A Phase I/II Trial of a Tetravalent Live Attenuated DEN Vaccine in Flavivirus Antibody Naive Children

Phase 1

Completed

Conditions: Dengue

Interventions: Biological: DEN vaccine F17

Registration Number: NCT01843621

Lead Sponsor: U.S. Army Medical Research and Development Command

Brief Summary: One year follow-up on immunogenicity and safety of a booster dose of DEN vaccine administered approx. 1 year following the second dose

Detailed Description: The purpose of this study is to find out more about the two doses of dengue vaccine, over a five year period, that the children received in the Dengue-003 study and to study a third dose of dengue that will be given to the children

* Do children still have dengue antibodies intended to provide protection against dengue infection one year after the two doses of vaccine given in study Dengue-003?

* Were there any major medical problems that appeared as dengue-like symptoms during the one year after vaccinations?

* Will a third dose of dengue help to further stimulate the part of the immune system intended to help protect against dengue infection?

* Is a third dose as safe as the first two doses?

* Are the local reactions to a third dose of the vaccine similar to what your child experienced after the first two doses?

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

Inclusion Criteria

Subjects who received two doses of DEN vaccine in the Dengue-003 study
Subjects whos parents signed an informed consent form were eligible for participation in the five year follow-up study

Exclusion Criteria

None

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Total vaccinated	DEN vaccine F17	The total vaccinated cohort included all enrolled subjects who received the DEN vaccine F17 for whom data were available. These subjects were Thai children previously enrolled and vaccinated in study Dengue-003

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects With Seropositivity Rates for Antibodies to DEN-1 - DEN-4 (ATP Cohort for Immunogenicity)	Prebooster Year 1, 30 Days Post Booster, Year 2, and Year 3	Neutralizing antibodies as measured by plaque reduction neutralization test (seropositivity rates to each dengue virus serotype at Prebooster Year 1, 30 Days Post Booster, Year 2, and Year 3 time points.
Geometric Mean Titers (GMTs) on All Subjects for Antibodies to DEN-1 - DEN-4 (ATP Cohort for Immunogenicity)	Prebooster Year 1, 30 Days Post Booster, Year 2, and Year 3	Neutralizing antibodies as measured by plaque reduction neutralization test (geometric mean titers \[GMTs\]) to each dengue virus serotype at Prebooster Year 1, 30 Days Post Booster, Year 2, and Year 3 time points.

Secondary Outcome Measures

Name	Time	Method
Solicited Local Adverse Events (AEs) Within 21 Day Follow-up	21 days	Incidence of solicited local symptoms reported during the 21-day post-vaccination (total vaccination cohort).
Unsolicited Adverse Events (AEs) Within 31 Days Post Vaccination	31 days	Percentage of subjects reporting unsolicited AEs within 31 days (Day 0-30) after the DEN vaccine dose (total vaccinated cohort)
Serious Adverse Events (SAE) Within 31 Days Post Vaccination	31 days	Occurrence of SAEs within 31 days (Day 0-30) after vaccination
Abnormal Findings Reported During Physical Exam 31-Days Post Vaccination	31 days	Incidence of dengue physical examination findings reported during the 31-day post-vaccination period (total vaccinated cohort)
Monovalent, Bivalent, Trivalent and Tetravalent Response for Neutralizing Antibodies 30 Days Post Booster	Prebooster year 1, 30 Days Post Booster, Year 2, Year 3	Monovalent, Bivalent, Trivalent and Tetravalent response for DEN neut. antibodies 30 days post booster dose vaccine (ATP cohort for immunogenicity)
Presence of Dengue Viremia 10 Days After the Dengue Vaccine Dose	10 days	Nested Polymerase Chain Reaction (PCR) for DEN was conducted on day 10 after DEN booster vaccination to evaluate the presence of Dengue viremia 10 days after vaccination
Flavivirus Infection in Terms of Dengue Immunoglobulin M and Immunoglobulin G Per Subject (ATP Cohort for Immunogenicity)	1 year, 30 Days Post Booster, 2 years	The ratio of DEN Immunoglobulin type M and G (IgM:IgG) measured at the time of booster vaccination and 30 days following was used to assess intercurrent flavivirus infection. Flavivirus infection in terms of dengue IgM and IgG and Japanese encephalitis virus (JEV) IgM and IgG is summarized. Flavivirus immunity= ratio IgM on IgG \<1.8 with either IgM or IgM \>1:40 If the antibody response is detectable by isotype capture enzyme immunoassay (either the IgM or IgG component ≥40 U), its anamnestic character can be inferred from detection of a DEN IgM to IgG ratio of \<1.8.
Subject Biochemistry and Hematology Parameters Monitored for Alert Levels	Year 1 (day 0); Year 1 (day 30); Year 2	Clinical safety laboratory test were monitored for alert levels. Tests were performed by Laser scattering using Cell Dyn 3500 and Serum chemistry conducted by Kinetic method using Hitachi 717. Normal Ranges: Alanine Aminotransferases (ALT): LNL=0 and UNL=30 Aspartate Aminotransferases (AST): LNL=0 and UNL=40 Platelet (PLA): LNL=150000 and UNL=350000 Hematocrit (HC): LNL=35 and UNL=45 Neutrophil (NEU): LNL=1500 and UNL=8000