Observer-blind, Single Center, Controlled Study of 2 Doses of Various Formulations of the WRAIR Live Attenuated Tetravalent Dengue Vaccine Compared to a Placebo Control, Administered on a 0-6-month Schedule, to Healthy Adults
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 86
- Locations
- 2
- Primary Endpoint
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Study Overview
Brief Summary
This descriptive study will evaluate the safety and immunogenicity of 5 different formulations of the WRAIR dengue vaccine compared to a placebo.
Detailed Description
Subjects will be randomized into one of 6 groups. One group will receive a placebo vaccine and the others will receive one of 5 different dengue vaccine formations. Each subject will receive two doses six months apart. Study subjects who elect to participate in a mosquito transmissibility component of the study will undergo mosquito feedings during each of the two assigned follow-up visits after vaccine dose 1. All subjects will have 11 venipunctures during 11 visits (i.e., screening plus 10 study visits) over a period of nine months.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
Eligibility Criteria
- Ages
- 18 Years to 45 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
DENGUE FORMULATION 17A GROUP
Healthy male or female subjects, between and including 18-45 years of age, who received two doses of Dengue vaccine Formulation 17a, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6.
Intervention: Live attenuated tetravalent dengue vaccine (Biological)
DENGUE FORMULATION 17B GROUP
Healthy male or female subjects, between and including 18-45 years of age, who received two primary doses of Dengue vaccine Formulation 17b, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6, and one booster dose approximately 5-12 months after the second dose.
Intervention: Live attenuated tetravalent dengue vaccine (Biological)
DENGUE FORMULATION 19 GROUP
Healthy male or female subjects, between and including 18-45 years of age, who received two primary doses of Dengue vaccine Formulation 19, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6 and one booster dose approximately 5-12 months after the second dose.
Intervention: Live attenuated tetravalent dengue vaccine (Biological)
PLACEBO GROUP
Healthy male or female subjects, between and including 18-45 years of age, who received two doses of Placebo, administered subcutaneously into the upper-outer triceps/deltoid area of the non-dominant arm, at Months 0 and 6.
Intervention: Placebo (Biological)
Outcomes
Primary Outcomes
Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Time Frame: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Time Frame: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
Assessed solicited general symptoms were abdominal pain, arthralgia, fatigue, fever \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\], headache, muscle aches, nausea, pain behind the eyes, photophobia, pruritus, rash and vomiting. Any = occurrence of the symptom regardless of intensity grade or relation to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever \> 39.0 °C. Related = symptom assessed by the investigator as causally related to the study vaccination.
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4
Time Frame: At 30 days (Month 7) after Dose 2 of the study vaccine
Titers for DEN-1, DEN-2, DEN-3 and DEN-4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum.
Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status
Time Frame: At Month 1 post-booster dose of the study vaccine
Titers for DEN 1, DEN 2, DEN 3 and DEN 4 neutralizing antibodies, expressed as Geometric Mean Titers (GMTs), with cut-off values greater than or equal to (≥) 10 estimated dose giving 50% (ED50) signal reduction when compared to a control without serum. Not primed = Not primed by MN50; Primed = Primed by MN50. Primed subject is a subject with neutralizing antibody titer ≥ 10 ED50 at pre-vaccination for at least one DEN type. Not primed subject is a subject with neutralizing antibody titer \<10 ED50 for any DEN type at pre-vaccination.
Secondary Outcomes
- Number of Subjects With Any and Grade 3 Solicited Local Symptoms(During the 21-day (Days 0-20) follow-up after the study vaccine booster dose)
- Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms(During the 21-day (Days 0-20) follow-up after the study vaccine booster dose)
- Number of Subjects With Unsolicited Adverse Events (AEs)(During the 31-day (Days 0-30) follow-up after any study vaccine dose)
- Number of Subjects With Serious Adverse Events (SAEs)(During the whole primary phase of the study (from Day 0 up to Month 9))
- Number of Subjects With Alert Values for Safety Laboratory Determinations(During the 31-day (Days 0-30) follow-up after the study vaccine booster dose)
- Number of Subjects With Abnormal Findings at Dengue Physical Examination(At Month 1 post-booster vaccination)
- Number of Subjects With Suspected and Confirmed Dengue(During the 31-day (Days 0-30) follow-up after the study vaccine booster dose)
- Number of Subjects With Measurable Dengue Viremia(At study Visit 12 (Days 2, 5, 8 or 12) (FU1), study Visit 13 post-booster vaccination (Days 5, 8, 12 or 14) (FU2) and at study Visit 14 (Month 1 post-booster vaccination))
- Number of Subjects With Safety Laboratory Determinations Outside the Normal Ranges(During the 31-day (Days 0-30) follow-up after each vaccine dose (Month 1 and Month 7))
- Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4(At Month 0 and Month 1)
- Number of Subjects With Antibody Titers Above the Assay Cut-off Value for Each DEN Serotype(Before (PRE) and one month after the booster vaccination (Month 1))
- Number of Subjects With Sero-response to Each DEN Type(At Months 1 and 7)
- Number of Subjects With Antibody Titers Above the Assay Cut-off Value (Tetravalent Response) for All Dengue Serotypes(At Months 1 and 7)
- Number of Subjects With Any, Grade 3 and Related Unsolicited AEs(During the 31-day (Days 0-30) follow-up after the study vaccine booster dose)
- Number of Subjects With SAEs(During the whole booster phase of the study (from pre-vaccination up to Month 6 post-vaccination with the booster dose))
- Number of Subjects With Hematological and Biochemical Determinations Within and Outside the Normal Ranges(At each booster phase visit [pre-booster vaccination (PRE), study Visit 12 post-booster vaccination (Days 2, 5, 8 or 12) (FU1), study Visit 13 post-booster vaccination (Days 5, 8, 12 or 14) (FU2) and at Months 1 and 6 post-booster vaccination])