Clinical trial NCT00350337: Safety and Immunogenicity of Various Formulations of Live Attenuated Tetravalent Dengue Vaccine in Healthy US Adults
Official title: Phase II, Randomized, Observer-Blind, Single Center, Controlled Study of Two Doses of Various Formulations of WRAIR Live Attenuated Tetravalent Dengue Vaccine Compared to Placebo Control Administered on 0-6-Month Schedule to Healthy Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dengue
Lead sponsor: U.S. Army Medical Research and Development Command
Sponsor class: FED
Collaborators: name: GlaxoSmithKline
name: Walter Reed Army Institute of Research (WRAIR)
First posted: 2006-07-10
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 3 different formulations of the WRAIR dengue vaccine compared to a placebo.

Detailed description: Subjects will be randomized into one of 4 groups. One group will receive a placebo vaccine and the others will receive one of 3 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.

A third (booster) dose of post transfection F17 or F19 will be administered approximately 5 to 12 months after dose 2 to all subjects who received one of these formulation for their first two doses. Volunteers will return for a single visit 6 months after receiving their booster dose (long term follow-up)

Eligibility criteria: Inclusion Criteria:

* A 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 (e.g., completion of the diary cards, return for follow-up visits) should be enrolled in the study;
* If the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (i.e. intrauterine contraceptive device; oral contraceptives or other equivalent hormonal contraception, e.g. progestin implantable, cutaneous hormonal patch or injectable contraceptives) 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 Criteria:

* Pregnant or lactating female;
* Female planning to become pregnant or planning to discontinue abstinence or contraceptive precautions;
* History of any neurological or behavioral disorder or seizures, with the exception of a single febrile seizure in childhood;
* History of drug abuse or alcohol consumption (more than 2 drinks per day);
* History of allergic disease/reaction likely to be exacerbated by any component of the vaccine;
* History of urticaria related to mosquito bites requiring medical attention;
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal, hematologic or endocrine functional defect, as determined by physical examination or laboratory tests;
* Any confirmed or suspected immunosuppressive or immunodeficient condition;
* Subject seropositive for HBsAg, anti-HCV or anti-HIV;
* Acute disease at the time of enrollment (acute disease is defined as the presence of a moderate or severe illness with or without fever);
* (Vaccine can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., oral temperature \<37.5°C/\<99.5°F.)
* Chronic hepatomegaly, right upper quadrant abdominal pain or tenderness;
* Chronic splenomegaly, left upper quadrant abdominal pain or tenderness;
* Use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the study vaccine (includes placebo) or planned use during the study period;
* Planned administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before each dose of the study vaccine and ending 30 days after;
* A planned move to a location that will prohibit participating in the trial for 9 months after the initial vaccination;
* Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 90 days preceding the first dose or planned administration during the study period. For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed;
* 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 (except for vitamin/mineral supplements, a single anti-hypertension medication or routine treatment for gastro-esophageal reflux).

Primary outcomes:
measure: N Antibody, Geometric Mean Titer(GMT) to Dengue Serotypes 1, 2, 3 and 4
timeFrame: Pre dose 1, 1 month post dose 1, 7 months post dose 2, Pre dose 3 and 1 month post dose 3
measure: Percentage of Subjects Seropositive for Dengue Serotypes 1, 2, 3 and 4
timeFrame: Pre dose 1, 1 month post dose 1, 7 months post dose 2, Pre dose 3 and 1 month post dose 3
measure: Occurrence of Any, and Grade 3 Solicited Adverse Events (AEs) Within 21 Days Follow-up After Dose 1 of Study Vaccine
timeFrame: 21 days following 1st vaccination dose
Secondary outcomes:
measure: Occurrence of Any, and Grade 3 Solicited Adverse Events (AEs) Within 21 Days Follow-up After Dose 2 of Study Vaccine;
timeFrame: within 21 days after vaccination
measure: Unsolicited Adverse Events Within 31 Days After Each Dose of Study Vaccine Dose
timeFrame: within 31 days of study vaccine
measure: Occurrence of Serious Adverse Events (SAEs) Throughout the Entire Study Period.
timeFrame: Days 0 to 270
measure: Occurrence of Abnormal Findings at Physical Examination After Each Vaccine Dose
timeFrame: throughout the 202 day study
measure: Percentage of Subjects With Suspected and Confirmed Dengue Reported During the 31-day Post-vaccination Period (Total Vaccinated Cohort)
timeFrame: Days 0-30 post vaccination periods (total vaccinated cohort)
measure: Neutralizing Antibody Sero-response to Each Dengue Serotype After Each Dose
timeFrame: Days 0 to 270
measure: Neutralizing Antibody Sero-response to Each Dengue Serotype After Each Dose (Continued)
timeFrame: Days 0 to 270
measure: Occurrence of Measurable Dengue Viremia at Specified Time Points Following Each Vaccine Dose.
timeFrame: Days 0 to 270
Other outcomes:
Locations:
city: Silver Spring
country: United States
facility: Walter Reed Army Institute of Research
state: Maryland
Study officials:
affiliation: Walter Reed Army Institute of Research (WRAIR)
name: Stephen J Thomas, MD, FACP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thomas SJ, Eckels KH, Carletti I, De La Barrera R, Dessy F, Fernandez S, Putnak R, Toussaint JF, Sun W, Bauer K, Gibbons RV, Innis BL. A phase II, randomized, safety and immunogenicity study of a re-derived, live-attenuated dengue virus vaccine in healthy adults. Am J Trop Med Hyg. 2013 Jan;88(1):73-88. doi: 10.4269/ajtmh.2012.12-0361. Epub 2012 Dec 3.