A Two-dose Primary Vaccination Study of a Tetravalent Dengue Virus Purified Inactivated Vaccine vs. Placebo in Healthy Adults (in Puerto Rico) (DPIV-002)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
GlaxoSmithKline
Walter Reed Army Institute of Research (WRAIR)
Information provided by (Responsible Party):
U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier:
NCT01702857
First received: October 4, 2012
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Dengue Fever
Biological: Biological/Vaccine: 4 µg TDENV-PIV with Alum adjuvant
Biological: Biological/Vaccine: 1 µg TDENV-PIV with AS03B adjuvant
Other: Phosphate buffered saline
Biological: 1 µg TDENV-PIV with Alum adjuvant
Biological: 1 µg TDENV-PIV with AS01E adjuvant
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by U.S. Army Medical Research and Materiel Command:

Primary Outcome Measures:
  • Safety and reactogenicity of various TDENV-PIV formulations from Day 0 through 28 days after the second dose (Day 0 - Day 56) [ Time Frame: Up to Day 56 ] [ Designated as safety issue: Yes ]

    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 56

  • Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations 28 days after the second dose (Day 56) [ Time Frame: Day 56 ] [ Designated as safety issue: No ]

    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:
  • Safety of various TDENV-PIV formulations, from Day 0 to Month 13 (Visits 1-11) [ Time Frame: Up to month 13 ] [ Designated as safety issue: Yes ]

    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 13

  • Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations on Days 0, 7 and 28 and Months 7 and 13 [ Time Frame: Up to month 13 ] [ Designated as safety issue: No ]

    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) [ Time Frame: Up to the end of study (Month 37-39) ] [ Designated as safety issue: Yes ]
    Occurrence of serious adverse events (SAEs) related to study procedures from Month 14 to end of study (Month 37-39)


Estimated Enrollment: 100
Study Start Date: October 2012
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TDENV-PIV alum4
4 µg TDENV-PIV with Alum adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
Biological: Biological/Vaccine: 4 µg TDENV-PIV with Alum adjuvant
Experimental: TDENV-PIV AS03B
1 µg TDENV-PIV with AS03B adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
Biological: Biological/Vaccine: 1 µg TDENV-PIV with AS03B adjuvant
Placebo Comparator: Placebo
Phosphate buffered saline; 0.5 mL intramuscular injection at 0 and 28 days
Other: Phosphate buffered saline
Experimental: TDENV-PIV alum1
1 µg TDENV-PIV with Alum adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
Biological: 1 µg TDENV-PIV with Alum adjuvant
Experimental: TDENV-PIV AS01E
1 µg TDENV-PIV with AS01E adjuvant; 0.5 mL intramuscular injection at 0 and 28 days
Biological: 1 µg TDENV-PIV with AS01E adjuvant

  Eligibility

Ages Eligible for Study:   20 Years to 39 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01702857

Locations
Puerto Rico
Clinical Research Center, 1st Floor University Hospital
San Juan, Puerto Rico, 00936-5067
Sponsors and Collaborators
U.S. Army Medical Research and Materiel Command
GlaxoSmithKline
Walter Reed Army Institute of Research (WRAIR)
Investigators
Principal Investigator: Clemente Diaz, MD University of Puerto Rico
  More Information

No publications provided

Responsible Party: U.S. Army Medical Research and Materiel Command
ClinicalTrials.gov Identifier: NCT01702857     History of Changes
Other Study ID Numbers: S-12-12, 116614, WRAIR 1945, DPIV-002
Study First Received: October 4, 2012
Last Updated: February 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by U.S. Army Medical Research and Materiel Command:
Dengue
Dengue fever
Dengue Hemorrhagic Fever
Flavivirus

Additional relevant MeSH terms:
Dengue
Arbovirus Infections
Flaviviridae Infections
Flavivirus Infections
Hemorrhagic Fevers, Viral
RNA Virus Infections
Virus Diseases
Aluminum Hydroxide
Aluminum sulfate
Adjuvants, Immunologic
Antacids
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 22, 2014