Clinical trial NCT01702857: A Two-dose Primary Vaccination Study of a Tetravalent Dengue Virus Purified Inactivated Vaccine vs. Placebo in Healthy Adults (in Puerto Rico)
Official title: A Phase I, Randomized, Placebo-Controlled, Observer-blind, Two-dose (0-28 Day Schedule) Primary Vaccination Study of WRAIR Tetravalent Dengue Virus Purified Inactivated Vaccine (TDENV-PIV) in Healthy Adults in Puerto Rico
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dengue Fever
Keywords: Dengue
Dengue fever
Dengue Hemorrhagic Fever
Flavivirus
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: 2012-10-10
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Primary outcomes:
measure: Safety and reactogenicity of various TDENV-PIV formulations from Day 0 through 28 days after the second dose (Day 0 - Day 56)
timeFrame: Up to Day 56
measure: Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations 28 days after the second dose (Day 56)
timeFrame: Day 56
Secondary outcomes:
measure: Safety of various TDENV-PIV formulations, from Day 0 to Month 13 (Visits 1-11)
timeFrame: Up to month 13
measure: Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations on Days 0, 7 and 28 and Months 7 and 13
timeFrame: Up to month 13
measure: • To evaluate the safety of various TDENV-PIV formulations from Month 14 through the end of the study (Visit 15)
timeFrame: Up to the end of study (Month 37-39)
Other outcomes:
Locations:
city: San Juan
country: Puerto Rico
facility: Clinical Research Center, 1st Floor University Hospital
Study officials:
affiliation: University of Puerto Rico
name: Clemente Diaz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Diaz C, Lin L, Martinez LJ, Eckels KH, Campos M, Jarman RG, De La Barrera R, Lepine E, Toussaint JF, Febo I, Innis BL, Thomas SJ, Schmidt AC. Phase I Randomized Study of a Tetravalent Dengue Purified Inactivated Vaccine in Healthy Adults from Puerto Rico. Am J Trop Med Hyg. 2018 May;98(5):1435-1443. doi: 10.4269/ajtmh.17-0627. Epub 2018 Mar 1.