Clinical Trial: A Phase I/II Trial of a Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naïve Children

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase I/II Trial of a Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naïve Children

Brief Summary: To assess the safety, reactogenicity and immunogenicity of two doses of the dengue vaccine in Flavi-virus antibody-naive children between 6 and 9 years of age.

Detailed Summary: This study was a Phase I/II, open-label trial with one treatment group; 7, healthy, flavivirus naïve children between the ages of 6 and 7 years residing in Bangkok, Thailand. Seronegative status was determined by measuring neutralizing (N) antibody titers to dengue 1-4 and JE virus (JE) using hemagglutination inhibition (HAI) (1st) and PRNT (2nd) assays. Titers <10 and <10, respectively, were considered negative. Enrolled children received two doses of tetravalent dengue vaccine at study months 0 and 6, and two doses of JE vaccine (study benefit) at study months 7 and 7.5. Enrolled children attended 20 study visits, received 4 injections, and 7 venipunctures (one additional blood sample for screening). In the acute period (1 month) following vaccination, safety was assessed using symptom diary cards and clinical and laboratory evaluations. Viremia was measured 10 days post dengue vaccination. Solicited and unsolicited adverse events were assessed for 30 days following each dengue vaccination. Serious adverse events were assessed throughout the study period. In the case of illness, investigators would complete additional clinical and virologic evaluations. Dengue vaccine immunogenicity was assessed 30 days following each dengue vaccination using the PRNT50 assay. The According to Protocol (ATP) cohort was determined by evaluating the occurrence of intermittent natural dengue infection using ELISA IgM/IgG titer ratios. A long-term follow-up of dengue vaccine recipients is described in a separate protocol (Dengue-005 protocol).
Sponsor: U.S. Army Medical Research and Materiel Command

Current Primary Outcome: Number of Solicited Adverse Events Within 21 Days After the First Dose of Dengue Vaccine. [ Time Frame: 21 days ]

Number of solicited general symptoms within the 21-day follow-up after dengue dose 1 (total vaccinated cohort).


Original Primary Outcome: To assess the reactogenicity in terms of solicited symptoms within the 21-day follow-up period after dose 1 of the dengue vaccine

Current Secondary Outcome:

  • Number of Unsolicited Adverse Events Within 30 Days After Each Dose of Dengue Vaccine [ Time Frame: 30 days ]
    Number of subjects with unsolicited symptoms classified by MedDRA Primary System Organ Class and Preferred Term, within 30 days after dengue vaccine (total vaccinated cohort)
  • Number of Solicited Adverse Events for 21 Days (0-20) After the Second Dose of Dengue Vaccine [ Time Frame: 21 Days (0-20) After the Second Dose of Dengue Vaccine ]
    Number of solicited general symptoms within the 21-day follow-up of dengue dose 2 vaccine dose (total vaccinated cohort)
  • Percentage of Individuals With Neutralizing Antibody (Seroconversion) to Japanese Encephalitis (JE) and 4 Dengue Types, 30 Days After the Second Dose of JE Vaccine. [ Time Frame: 30 days after the second dose of JE vaccine ]
    Percentage of individuals with ≥ 10 dilution (DIL) for neutralizing (N) Ig to DEN-1, N Ig to DEN-2, N Ig to DEN-3, N Ig to DEN-4, and N Ig to Japanese encephalitis (JE) vaccine antibody titers.
  • Neutralizing Antibody (GMT) to JE and 4 Dengue Types, 30 Days After the Second Dose of JE Vaccine. [ Time Frame: Approximately Day 225 and Day 255 ]
    Geometric mean titers (GMT) for neutralizing (N) Ig to DEN-1, N Ig to DEN-2, N Ig to DEN-3, N Ig to DEN-4, and N Ig to JE vaccine antibody titers.
  • Number of Solicited Symptoms 7 Days (0-6) After First Dose of Japanese Encephalitis (JE) Vaccine. [ Time Frame: Approximately Day 225 and Day 255 ]
    Number of solicited general symptoms within the 7-day follow-up after the first dose of Japanese encephalitis (JE) vaccine doses (total vaccinated cohort)
  • Number of Solicited Symptoms 7 Days (0-6) After Second Dose of Japanese Encephalitis (JE) Vaccine. [ Time Frame: Approximately Day 225 and Day 255 ]
    Number of solicited general symptoms within the 7-day follow-up after the second dose of Japanese encephalitis (JE) vaccine doses (total vaccinated cohort)


Original Secondary Outcome:

  • To assess the safety and reactogenicity of two doses of the dengue vaccine
  • To assess the immunogenicity of the dengue vaccine by seroconversion 30 days post-dose 2 of dengue vaccine
  • To assess the immunogenicity of the dengue vaccine by measurement of neutralizing antibodies to each dengue virus serotype 30 days after each dose of dengue vaccine
  • To assess the immunogenicity of the JE vaccine by measurement of neutralizing antibodies 30 days after dose 2 of JE vaccine
  • To assess the safety and reactogenicity after each dose of JE vaccine given 1 and 1.5 months after completion of the dengue vaccination course.


Information By: U.S. Army Medical Research and Materiel Command

Dates:
Date Received: October 4, 2006
Date Started: August 2003
Date Completion:
Last Updated: January 10, 2014
Last Verified: January 2014