Clinical trial NCT00239577: A Trial of a Walter Reed Army Institute of Research (WRAIR) Live Attenuated Virus Tetravalent Dengue Vaccine in Healthy US Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dengue
Keywords: Dengue infection
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-10-17
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: Inclusion:

* Healthy male or female adult 18-45 years at the time of vaccination
* Free of obvious health problems as established by medical history and physical examination before entering into the study
* Written informed consent obtained from the subject
* Able to read the Subject Information Sheet and Consent Form
* Subjects who the investigator believes can and will comply with the requirements of the protocol
* Females must be of non-childbearing potential, or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions as defined in the protocol for 30 days prior to vaccination, have a negative pregnancy test within 48 hours prior to vaccination and must agree to continue such precautions for 60 days after completion of the vaccination series

Exclusion:

History of:

* recurrent migraine headache
* any neurological or behavioral disorder or seizures
* drug abuse or alcohol consumption (more than 2 drinks per day)
* allergic disease/reaction likely to be exacerbated by vaccine
* urticaria related to mosquito bites requiring medical attention
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal, hematologic or endocrine functional defect
* Any confirmed or suspected immunosuppressive or immunodeficient condition;
* Seropositive for HBsAg, anti-HCV or anti-HIV
* Acute disease at the time of enrollment
* Chronic hepatomegaly or splenomegaly
* Use of any investigational or non-registered drug or vaccine within 30 days preceding study or planned use
* Planned administration of a vaccine not foreseen by the study protocol 30 days ±each vaccine dose
* Planned move during study
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs or administration of immunoglobulins and/or blood products, within 90 days preceding the first dose or planned administration during the study period
* Any chronic systemic drug therapy to be continued during the study period

Primary outcomes:
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 21-day (Days 0-20) follow-up after Dose 1 of the study vaccine
measure: Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4
timeFrame: At 30 days (Month 7) after Dose 2 of the study vaccine
measure: Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status
timeFrame: At 5 to 12 months post-Dose 2 of the study vaccine
measure: Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4 Based on Priming Status
timeFrame: At Month 1 post-booster dose of the study vaccine
Secondary outcomes:
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 21-day (Days 0-20) follow-up after Dose 2 of the study vaccine
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 21-day (Days 0-20) follow-up after Dose 2 of the study vaccine
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 21-day (Days 0-20) follow-up after each dose of the study vaccine
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 21-day (Days 0-20) follow-up after each dose of the study vaccine
measure: Number of Subjects With Unsolicited Adverse Events (AEs)
timeFrame: During the 31-day (Days 0-30) follow-up after any study vaccine dose
measure: Number of Subjects With Serious Adverse Events (SAEs)
timeFrame: During the whole primary phase of the study (from Day 0 up to Month 9)
measure: Number of Subjects With Alert Values for Safety Laboratory Determinations
timeFrame: During the 31-day (Days 0-30) follow-up after each vaccine dose (Month 1 and Month 7)
measure: Number of Subjects With Abnormal Findings at Dengue Physical Examination
timeFrame: During the 31-day (Days 0-30) follow-up after each vaccine dose and across doses
measure: Number of Subjects With Suspected and Confirmed Dengue
timeFrame: During the 31-day (Days 0-30) follow-up after each vaccine dose and across doses
measure: Number of Subjects With Measurable Dengue Viremia
timeFrame: During the 31-day (Days 0-30) follow-up after each vaccine dose
measure: Number of Subjects With Safety Laboratory Determinations Outside the Normal Ranges
timeFrame: During the 31-day (Days 0-30) follow-up after each vaccine dose (Month 1 and Month 7)
measure: Titers for DEN Neutralizing Antibodies Types 1, 2, 3 and 4
timeFrame: At Month 0 and Month 1
measure: Number of Subjects With Antibody Titers Above the Assay Cut-off Value for Each DEN Serotype
timeFrame: At Months 0, 1 and 7
measure: Number of Subjects With Antibody Titers Above the Assay Cut-off Value (Tetravalent Response) for All Dengue Serotypes
timeFrame: At Months 1 and 7
measure: Number of Subjects With Sero-response to Each DEN Type
timeFrame: At Months 1 and 7
measure: Number of Subjects With Any and Grade 3 Solicited Local Symptoms
timeFrame: During the 21-day (Days 0-20) follow-up after the study vaccine booster dose
measure: Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
timeFrame: During the 21-day (Days 0-20) follow-up after the study vaccine booster dose
measure: Number of Subjects With Any, Grade 3 and Related Unsolicited AEs
timeFrame: During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
measure: Number of Subjects With SAEs
timeFrame: During the whole booster phase of the study (from pre-vaccination up to Month 6 post-vaccination with the booster dose)
measure: Number of Subjects With Hematological and Biochemical Determinations Within and Outside the Normal Ranges
timeFrame: 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]
measure: Number of Subjects With Alert Values for Safety Laboratory Determinations
timeFrame: During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
measure: Number of Subjects With Abnormal Findings at Dengue Physical Examination
timeFrame: At Month 1 post-booster vaccination
measure: Number of Subjects With Suspected and Confirmed Dengue
timeFrame: During the 31-day (Days 0-30) follow-up after the study vaccine booster dose
measure: Number of Subjects With Measurable Dengue Viremia
timeFrame: 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)
measure: Number of Subjects With Antibody Titers Above the Assay Cut-off Value for Each DEN Serotype
timeFrame: Before (PRE) and one month after the booster vaccination (Month 1)
Other outcomes:
Locations:
city: Silver Spring
country: United States
facility: GSK Investigational Site
state: Maryland
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: