a two-dose primary vaccination study of a tetravalent dengue virus purified inactivated vaccine vs. placebo in healthy adults (in puerto rico)

Conditions: Dengue Fever

Summary: this is a first time in humans (ftih) study designed to assess the experimental tdenv-piv vaccine in a predominantly dengue-primed adult population. the study is designed to afford a first time in humans (ftih) safety and immunogenicity assessment of three tdenv-piv vaccine candidates, each formulated with a different adjuvant: either aluminum hydroxide, as01e or as03b (adjuvants used in gsk biologicals' hepatitis b candidate vaccine, malaria candidate vaccine and pandemic flu vaccine, respectively). each vaccine candidate will contain 1 µg of purified virus antigen per each of the four denv types. additionally, the study will evaluate an alum adjuvanted tdenv-piv vaccine candidate containing 4 µg of purified virus antigen per each of the four denv types. the control group will receive a saline placebo. all experimental vaccinations will be administered according to a 2-dose schedule, 28 days apart. there is a parallel ftih study that is conducted in the united states in a dengue-naive population using the same investigational vaccines.


Eligibility criteria:
inclusion criteria: * 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, etc.) * a male or female between 20 and 39 years of age (inclusive) at the time of consent * written informed consent obtained from the subject * healthy subjects as established by medical history and clinical examination before entering into the study * subject has lived in the caribbean for more than 10 years * female subjects of non-childbearing potential (non-childbearing potential is defined as having either a current tubal ligation at least three months prior to enrollment, hysterectomy, ovariectomy, or is post-menopause). * female subjects of childbearing potential may be enrolled in the study, if the subject has: * practiced adequate contraception for 30 days prior to vaccination, and * a negative urine pregnancy test on the day of vaccination, and * agreed to continue adequate contraception until two months after completion of the vaccination series exclusion criteria: * use of any investigational or non-registered product (drug or vaccine) other than the study vaccines/placebo during the period starting 30 days preceding the first dose of study vaccine/placebo and/or planned use during the study period * chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 180 days prior to the first vaccine/placebo dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day or equivalent; inhaled and topical steroids are allowed) * planned administration or administration of a vaccine/product not foreseen by the study protocol during the exclusion: * use of any investigational or non-registered product (drug or vaccine) other than the study vaccines/placebo during the period starting 30 days preceding the first dose of study vaccine/placebo and/or planned use during the study period * chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 180 days prior to the first vaccine/placebo dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day or equivalent; inhaled and topical steroids are allowed) * planned administration or administration of a vaccine/product not foreseen by the study protocol during the period starting 30 days prior to the first dose of vaccine/placebo until after the visit at day 56 (if influenza activity warrants vaccination of healthy young adults, influenza vaccination will be encouraged and will not lead to study exclusion) * previous or planned administration of any other flavivirus vaccine (approved or investigational) for the entire study duration * previous receipt of any investigational dengue virus vaccine * concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). * any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). * family history of congenital or hereditary immunodeficiency * history of, or current auto-immune disease * history of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine/placebo or related to a study procedure * major congenital defects or serious chronic illness * history of any neurological disorders or seizures * acute disease and/or fever (≥37.5°c/99.5°f oral body temperature) at the time of enrollment (a subject with a minor illness, i.e., mild diarrhea, mild upper respiratory infection, etc., without fever, may be enrolled at the discretion of the investigator) * acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests * administration of immunoglobulins and/or any blood products during the period starting 90 days preceding the first dose of study vaccine/placebo or planned administration during the study period * history of chronic alcohol consumption and/or drug abuse * pregnant or lactating female or female planning to become pregnant or planning to discontinue contraceptive precautions * a planned move to a location that will prohibit participating in the trial until study end for the participant * any other condition which, in the opinion of the investigator, prevents the subject from participating in the study. * subject seropositive for hepatitis b surface antigen (hbsag), hepatitis c virus antibodies (anti-hcv), or human immunodeficiency virus antibodies (anti-hiv) * safety laboratory test results that are outside the normal limits for their age, gender, and locality at screening.

Keywords: dengue dengue fever dengue hemorrhagic fever flavivirus