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

NCT01702857 | Completed Phase 1 DMC

• 4 other identifiers: S-12-12116614WRAIR 1945DPIV-002
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

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.

Conditions

Dengue Fever

Keywords

Dengue; Dengue fever; Dengue Hemorrhagic Fever; Flavivirus

Outcome Measures

Primary Outcomes (2)

• Safety and reactogenicity of various TDENV-PIV formulations from Day 0 through 28 days after the second dose (Day 0 - 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 56

  Up to Day 56

• Humoral immunogenicity to each of four DENV types of various TDENV-PIV formulations 28 days after the second dose (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

  Day 56

Secondary Outcomes (3)

• Safety of various TDENV-PIV formulations, from Day 0 to Month 13 (Visits 1-11)

  Up 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

  Up to month 13

• • 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)

Study Arms (5)

TDENV-PIV alum4

EXPERIMENTAL

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

TDENV-PIV AS03B

EXPERIMENTAL

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

PLACEBO COMPARATOR

Phosphate buffered saline; 0.5 mL intramuscular injection at 0 and 28 days

Other: Phosphate buffered saline

TDENV-PIV alum1

EXPERIMENTAL

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

TDENV-PIV AS01E

EXPERIMENTAL

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

Interventions

Biological/Vaccine: 4 µg TDENV-PIV with Alum adjuvant BIOLOGICAL

TDENV-PIV alum4

Biological/Vaccine: 1 µg TDENV-PIV with AS03B adjuvant BIOLOGICAL

TDENV-PIV AS03B

Phosphate buffered saline OTHER

Placebo

1 µg TDENV-PIV with Alum adjuvant BIOLOGICAL

TDENV-PIV alum1

1 µg TDENV-PIV with AS01E adjuvant BIOLOGICAL

TDENV-PIV AS01E

Eligibility Criteria

• Age: 20 Years - 39 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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)
• 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

Sponsors & Collaborators

• U.S. Army Medical Research and Development Command: lead
• GlaxoSmithKline: collaborator
• Walter Reed Army Institute of Research (WRAIR): collaborator

Study Sites (1)

Clinical Research Center, 1st Floor University Hospital

San Juan, 00936-5067, Puerto Rico

Location

Related Publications (1)

• 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.

  PMID: 29512481 DERIVED

MeSH Terms

Conditions

Dengue; Severe Dengue

Interventions

Biological Products; Vaccines; Aluminum Hydroxide

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Intervention Hierarchy (Ancestors)

Complex Mixtures; Hydroxides; Alkalies; Inorganic Chemicals; Aluminum Compounds; Anions; Ions; Electrolytes

Study Officials

• Clemente Diaz, MD

  University of Puerto Rico

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 4, 2012
• First Posted: October 10, 2012
• Study Start: November 1, 2012
• Primary Completion: January 20, 2017
• Study Completion: March 23, 2017
• Last Updated: May 23, 2017

Record last verified: 2017-05

Locations

PR (1)