Clinical trial NCT01666652: A Two-dose Primary Vaccination Study of a Tetravalent Dengue Virus Purified Inactivated Vaccine vs. Placebo in Healthy Adults
Official title: A Phase I, Randomized, Placebo-Controlled, Observer-blind, Two-dose (0-28 Day Schedule) Primary Vaccination Study of Walter Reed Army Institute of Research (WRAIR) Tetravalent Dengue Virus Purified Inactivated Vaccine (TDENV-PIV) in Healthy Adults in a Non-Endemic Region
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: 2012-08-16
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 39
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The study is designed to afford a safety and immunogenicity assessment of three Tetravalent Dengue Virus-Purified Inactivated Vaccine(TDENV-PIV) vaccine candidates.

Detailed description: The study is designed to afford a safety and immunogenicity assessment of three Tetravalent Dengue Virus-Purified Inactivated Vaccine(TDENV-PIV) vaccine candidates, each formulated with a different adjuvant: either aluminum hydroxide, AS01E or AS03B (adjuvants used in Glaxo Smith Kline (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.

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 18 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
* 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). See Definition of Terms for adequate contraception.
* 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 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)
* Planned administration of any flavivirus vaccine for the entire study duration
* 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 acceptable values at screening. The following values are not acceptable:

  * \>110% upper limit of normal (ULN) for alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, creatinine, serum urea nitrogen (SUN) and bilirubin (total and direct)
  * \<100% lower limit of normal (LLN) or \> 120% ULN for hemoglobin, hematocrit and platelet count
  * \<75% LLN or \>110% ULN for total white blood cell count (WBC) Note that all screening laboratory results must be either within normal limits (WNL) or no more than Grade l not clinically significant (NCS)

(LLN=lower limit of normal; ULN= upper limit of normal, WNL= within normal limits, NCS= not clinically significant)

Primary outcomes:
measure: Number of Subjects With Adverse Events Within the 28 Day Follow-up
timeFrame: Days 0-28
measure: Incidence of Any Symptoms (Solicited and Unsolicited) Reported During the 7-day Post Vaccination Period. Total Vaccinated Cohort (TVC)
timeFrame: Days 0-6 post vaccination
measure: Incidence of General Symptoms (Solicited and Unsolicited) Reported During the 7-day Post Vaccination Period, Total Vaccinated Cohort (TVC)
timeFrame: Days 0-6 post vaccination
measure: Incidence of Local Symptoms (Solicited and Unsolicited) Reported During the 7-day Post Vaccination Period, Total Vaccinated Cohort (TVC)
timeFrame: Days 0-6 post vaccination
measure: Summary of Subjects With Serious Adverse Events
timeFrame: days 0-392
Secondary outcomes:
measure: Number of Subjects With Laboratory Values Within and Outside the Normal Ranges and With Different Grade of Adverse Event From Screening to Day 56 Visit
timeFrame: day 56 visit
measure: Geometric Mean Titers (GMTs) of Neutralizing Antibody Titers Specific to Each DENV Type - According to Protocol Population (ATP)
timeFrame: up to month 13
measure: Number of Subject Showing Monovalent, Bivalent, Trivalent and Tetravalent Response for Neutralizing Antibodies - Total Vaccinated Cohort (TVC)
timeFrame: up to month 13
Other outcomes:
Locations:
city: Silver Spring
country: United States
facility: WRAIR, Clinical Trials Center
state: Maryland
Study officials:
affiliation: Walter Reed Army Institute of Research (WRAIR)
name: Leyi Lin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schmidt AC, Lin L, Martinez LJ, Ruck RC, Eckels KH, Collard A, De La Barrera R, Paolino KM, Toussaint JF, Lepine E, Innis BL, Jarman RG, Thomas SJ. Phase 1 Randomized Study of a Tetravalent Dengue Purified Inactivated Vaccine in Healthy Adults in the United States. Am J Trop Med Hyg. 2017 Jun;96(6):1325-1337. doi: 10.4269/ajtmh.16-0634.