A Phase I/II Trial of Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naive Infants

NCT00322049 Phase 1/Phase 2 COMPLETED Results posted

The main target populations for the tetravalent live attenuated dengue virus vaccine are indigenous populations, especially infants less than 2 years old, residing in areas of the world endemic for dengue and at risk of developing dengue hemorrhagic fever (DHF). The presence of maternal dengue antibody during the first year of life makes it unlikely that a vaccine given during that time will have long-term efficacy, as the vaccine virus would likely be neutralized prior to necessary replication. Children older than 18 months may have preexisting flavivirus antibody. Therefore, vaccination of infants living in Thailand early in the second year of life (between the ages of 12 and 18 months) seems most beneficial. The aim of this trial is to evaluate the safety and immunogenicity of a two-dose schedule of a tetravalent live attenuated dengue vaccine in flavivirus antibody naïve infants beginning at 12-15 months of age. * To assess the kinetics of dengue neutralizing antibodies to each dengue virus serotype one and four years following dose 2 of dengue/control vaccination in the setting of potential wild-type dengue virus exposure. * To assess the immunogenicity, the safety and reactogenicity of a booster dose of dengue vaccine administered at Year 3 following primary vaccination.

Details

Lead sponsor	U.S. Army Medical Research and Development Command
Phase	Phase 1/Phase 2
Status	COMPLETED
Enrolment	51
Start date	2004-02
Completion	2009-06

Conditions

• Dengue

Interventions

• Tetravalent live attenuated dengue vaccine
• Varicella vaccine and Haemophilus influenzae Type b Conjugate vaccine

Primary outcomes

• Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. — 21-day follow-up period after Dose 1
  Local and general solicited reactogenicity using diary cards for 21 days (days 0-20) after the first dose of dengue/control vaccine
• Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine — 30 days post Dose 2
  Assess the immunogenicity of the dengue vaccine in terms of GMTs 30 days post-Dose 2 of dengue vaccine for all four serotypes (DEN-1, 2, 3, 4 and JE (Japanese encephalitis)). Analysis of immunogenicity was performed on the ATP cohort.
• Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 — month 7 after dose 2
  Seronegative for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2. Seronegative (antibody titer \<10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.
• Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE — month 8.5
  Seropositivity for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2 (and 2 doses of JE). Seronegative (antibody titer \<10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.
• JE Vaccine Response — Pre-vaccination, 1, 6, 7 and 8.5 months after two doses of dengue vaccine
  Seropositivity rates and GMTs for N lg to JEV antibodies. Pre= Pre vaccination, blood sampling prior to the first vaccine dose; PI(M1)= Post 1, month 1, blood sampling one month after dose 1 at study month 1; PI(M6)= Post 1, month 6, blood sampling 6 months after dose 1 at study month 6; PII(M7)= Post II, month 7, blood sampling one month after dose 2 at study month 7; PIV(M8.5)= Post IV, month 8.5, blood sampling after 2 doses of dengue/control and 2 doses of JE vaccines at study month 8.5

Countries

Thailand