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
- Interventions
- Biological: 1 µg TDENV-PIV with Alum adjuvantBiological: 1 µg TDENV-PIV with AS01E adjuvantOther: Phosphate buffered saline
- Registration Number
- NCT01702857
- Lead Sponsor
- U.S. Army Medical Research and Development Command
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 100
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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.)
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A male or female between 20 and 39 years of age (inclusive) at the time of consent
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Written informed consent obtained from the subject
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Healthy subjects as established by medical history and clinical examination before entering into the study
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Subject has lived in the Caribbean for more than 10 years
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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).
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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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TDENV-PIV alum1 1 µg TDENV-PIV with Alum adjuvant 1 µg TDENV-PIV with Alum adjuvant; 0.5 mL intramuscular injection at 0 and 28 days TDENV-PIV AS01E 1 µg TDENV-PIV with AS01E adjuvant 1 µg TDENV-PIV with AS01E adjuvant; 0.5 mL intramuscular injection at 0 and 28 days Placebo Phosphate buffered saline Phosphate buffered saline; 0.5 mL intramuscular injection at 0 and 28 days
- Primary Outcome Measures
Name Time Method Safety and reactogenicity of various TDENV-PIV formulations from Day 0 through 28 days after the second dose (Day 0 - Day 56) Up to Day 56 Safety and Reactogenicity:
* Occurrence, intensity and relationship to vaccination of solicited local and general adverse events (AEs) during the 7-day follow-up period post each vaccination (Day 0-6)
* Occurrence, intensity and relationship to vaccination of unsolicited AEs during the 28-day follow-up period post each vaccination (Day 0-27)
* Hematological and biochemical levels at study visits on Days 0, 7, 28, 35 and 56
* Occurrence of serious adverse events (SAEs) from Day 0 to Day 56
* Occurrence of potential immune-mediated diseases (pIMDs) and medically attended AEs from Day 0 to Day 56Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations 28 days after the second dose (Day 56) Day 56 Humoral Immunogenicity:
Neutralizing antibody titers specific to each DENV type at Day 56
* Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type
* Rate of fold increases in neutralizing antibody from Day 0 for each DENV type
* Seropositivity rates for each DENV type
* Trivalent and tetravalent seropositivity rates
- Secondary Outcome Measures
Name Time Method Safety of various TDENV-PIV formulations, from Day 0 to Month 13 (Visits 1-11) Up to month 13 Safety:
* Hematological and biochemical levels at study visits on Months 4, 7, 10 and Month 13
* Occurrence of pIMDs and medically attended AEs from Day 0 to Month 13
* Occurrence of any SAE from Day 0 to Month 13Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations on Days 0, 7 and 28 and Months 7 and 13 Up to month 13 Humoral Immunogenicity:
* Geometric mean titers (GMTs) of neutralizing antibody titers to each DENV type
* Rate of fold increases in neutralizing antibody from Day 0 for each DENV type
* Seropositivity rates for each DENV type
* Trivalent and tetravalent seropositivity rates• To evaluate the safety of various TDENV-PIV formulations from Month 14 through the end of the study (Visit 15) Up to the end of study (Month 37-39) Occurrence of serious adverse events (SAEs) related to study procedures from Month 14 to end of study (Month 37-39)
Trial Locations
- Locations (1)
Clinical Research Center, 1st Floor University Hospital
🇵🇷San Juan, Puerto Rico