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

• ClinicalTrials.gov Identifier: NCT01843621
• Recruitment Status: Completed
• First Posted: April 30, 2013
• Results First Posted: November 26, 2018
• Last Update Posted: November 26, 2018
• Sponsor: U.S. Army Medical Research and Development Command
• Collaborator: GlaxoSmithKline
• Information provided by (Responsible Party): U.S. Army Medical Research and Development Command

Study Description

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

Condition or disease	Intervention/treatment	Phase
Dengue	Biological: DEN vaccine F17	Phase 1; Phase 2

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?

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Phase I/II, Open, Five-year, Clinical Follow-up Study of Thai Children Who Participated in Dengue-003 ("A Phase I/II Trial of a Tetravalent Live Attenuated DEN Vaccine in Flavivirus Antibody Naive Children") With Evaluation of a Booster Dose Given One Year After Primary DEN Vaccination Series
• Study Start Date: February 2005
• Actual Primary Completion Date: February 2005
• Actual Study Completion Date: February 2009

Arms and Interventions

Arm	Intervention/treatment
Experimental: Total vaccinated; 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	Biological: DEN vaccine F17; The dengue booster vaccine was administered subcutaneously in the non-dominant arm (deltoid). The tetravalent, live attenuated DEN F17 vaccine was administered in this study. This pre-transfection formulation contained dengue virus types 1, 2, 3 and 4 (DEN-1, -2, -3 and -4).; Other Name: Live attenuated tetravalent dengue (DEN) vaccine

Outcome Measures

Primary Outcome Measures :

1. Percentage of Subjects With Seropositivity Rates for Antibodies to DEN-1 - DEN-4 (ATP Cohort for Immunogenicity) [ Time Frame: 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.
2. Geometric Mean Titers (GMTs) on All Subjects for Antibodies to DEN-1 - DEN-4 (ATP Cohort for Immunogenicity) [ Time Frame: 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 :

1. Solicited Local Adverse Events (AEs) Within 21 Day Follow-up [ Time Frame: 21 days ]
   Incidence of solicited local symptoms reported during the 21-day post-vaccination (total vaccination cohort).
2. Unsolicited Adverse Events (AEs) Within 31 Days Post Vaccination [ Time Frame: 31 days ]
   Percentage of subjects reporting unsolicited AEs within 31 days (Day 0-30) after the DEN vaccine dose (total vaccinated cohort)
3. Serious Adverse Events (SAE) Within 31 Days Post Vaccination [ Time Frame: 31 days ]
   Occurrence of SAEs within 31 days (Day 0-30) after vaccination
4. Abnormal Findings Reported During Physical Exam 31-Days Post Vaccination [ Time Frame: 31 days ]
   Incidence of dengue physical examination findings reported during the 31-day post-vaccination period (total vaccinated cohort)
5. Monovalent, Bivalent, Trivalent and Tetravalent Response for Neutralizing Antibodies 30 Days Post Booster [ Time Frame: 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)
6. Presence of Dengue Viremia 10 Days After the Dengue Vaccine Dose [ Time Frame: 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
7. Flavivirus Infection in Terms of Dengue Immunoglobulin M and Immunoglobulin G Per Subject (ATP Cohort for Immunogenicity) [ Time Frame: 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.

8. Subject Biochemistry and Hematology Parameters Monitored for Alert Levels [ Time Frame: 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

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 9 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Thailand

Department of Pediatrics, Phramongkutklao Hospital

Phayathai, Bangkok, Thailand, 10400

Sponsors and Collaborators

U.S. Army Medical Research and Development Command

GlaxoSmithKline

Investigators

• Principal Investigator: Sriluck Simasathien, M.D.; Department of Pediatrics, Phramongkutklao Hospital, Bangkok, Thailand
• Principal Investigator: Robert Gibbons, M.D.; Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, Thailand

More Information

• Responsible Party: U.S. Army Medical Research and Development Command
• ClinicalTrials.gov Identifier: NCT01843621
• Obsolete Identifiers: NCT00318916
• Other Study ID Numbers: A-13227; GSK 103795 ( Other Identifier: GSK ); WRAIR 1159 ( Other Identifier: WRAIR )
• First Posted: April 30, 2013
• Results First Posted: November 26, 2018
• Last Update Posted: November 26, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: GSK

Keywords provided by U.S. Army Medical Research and Development Command:

Dengue, Vaccine, Thailand

Additional relevant MeSH terms:

Dengue; Arbovirus Infections; Vector Borne Diseases; Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Vaccines; Immunologic Factors; Physiological Effects of Drugs