Study of Varying Injection Schedules of TDENV-PIV Vaccine With AS03B Adjuvant and Placebo in Healthy US Adults

NCT02421367 | Completed Phase 1

• 3 other identifiers: S-14-13WRAIR # 2195201658
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 2

Brief Summary

This study is being conducted to evaluate the safety and immunogenicity and antibody persistence of the candidate dengue vaccine.

Conditions

Dengue

Outcome Measures

Primary Outcomes (12)

• Number of solicited local adverse events related to product

  7-day follow-up period after each dose

• Intensity of solicited local adverse events related to product

  7-day follow-up period after each dose

• Number of unsolicited adverse events related to product

  28-day follow-up period after each dose

• Intensity of unsolicited adverse events related to product

  28-day follow-up period after each dose

• Number of Grade 2 laboratory abnormalities

  7-day follow-up period after each dose

• Number of Grade 3 laboratory abnormalities

  7-day follow-up period after each dose

• Number of serious adverse events from day 0 through 28 days after the last dose

  7 months after first dose

• Number of potential immune-mediated diseases from Day 0 through 28 days after the last dose

  7 months after first dose

• Neutralizing antibody titers to each DENV type

  Day 0 and 28 days after the second and third doses of TDENV-PIV

• Number of general adverse events related to product

  7-day follow-up period after each dose

• Intensity of solicited general adverse events related to product

  7-day follow-up period after each dose

• Number of medically attended AEs related to product

  Day 0 through 28 days after the last dose

Secondary Outcomes (16)

• Number of potential immune-mediated diseases from post Month 7 to Study End

  7 months after first dose to the end of study

• Number of serious adverse events related to product

  7 months after first dose to the end of study

• Neutralizing antibody titers to each DENV type

  56 days after the second dose of active vaccine

• Seropositivity status for each DENV type

  28 days after the second dose of active vaccine for all groups

• Number of medically attended AEs from post Month 7 to Study End

  7 months after first dose to the end of study

Study Arms (3)

TDENV-PIV (0-1)

EXPERIMENTAL

The intervention is a tetravalent dengue virus purified inactivated vaccine (1µg/DENV type) with adjuvant, AS03B. The placebo is sodium chloride. TDENV-PIV vaccine and placebo will be administered in a single 0.5 mL dose intramuscularly in the non-dominant (whenever possible) deltoid region of the upper arm. The intervention will be administered on Day 0 and Day 28. The placebo will be administered on Day 84 and Day 168.

Biological: TDENV-PIV with AS03B adjuvant. Placebo: 0.9% Sodium Chloride Solution.

TDENV-PIV (0-1-6)

EXPERIMENTAL

The intervention is a tetravalent dengue virus purified inactivated vaccine (1µg/DENV type) with adjuvant, AS03B. The placebo is sodium chloride. TDENV-PIV vaccine and placebo will be administered in a single 0.5 mL dose intramuscularly in the non-dominant (whenever possible) deltoid region of the upper arm. The intervention will be administered on Day 0, Day 28, and Day 168. The placebo will be administered on Day 84.

Biological: TDENV-PIV with AS03B adjuvant. Placebo: 0.9% Sodium Chloride Solution.

TDENV-PIV (0-3)

EXPERIMENTAL

The intervention is a tetravalent dengue virus purified inactivated vaccine (1µg/DENV type) with adjuvant, AS03B. The placebo is sodium chloride. TDENV-PIV vaccine and placebo will be administered in a single 0.5 mL dose intramuscularly in the non-dominant (whenever possible) deltoid region of the upper arm. The intervention will be administered on Day 84 and Day 168. The placebo will be administered on Day 0 and Day 28.

Biological: TDENV-PIV with AS03B adjuvant. Placebo: 0.9% Sodium Chloride Solution.

Interventions

TDENV-PIV with AS03B adjuvant. Placebo: 0.9% Sodium Chloride Solution. BIOLOGICAL

Tetravalent dengue virus purified inactivated vaccine (1 µg/virus type)

TDENV-PIV (0-1); TDENV-PIV (0-1-6); TDENV-PIV (0-3)

Eligibility Criteria

• Age: 20 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects must be able to provide written informed consent.
• Subjects must be healthy as established by medical history and clinical examination at study entry
• 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.)
• Subjects at WRAIR CTC must be able to pass Department of Defense (DoD) base entry requirements, including the possession of a valid government issued ID card.
• Male or non-pregnant, non-breastfeeding female between 20 and 49 years of age (inclusive) at the time of consent
• Female subjects of non-childbearing potential (non-childbearing potential is defined as having had one of the following: a tubal ligation at least 3 months prior to enrollment, a hysterectomy, an ovariectomy, or is post-menopausal).
• Female subjects of childbearing potential may be enrolled in the study, if all of the following apply:
• Practiced adequate contraception (see Definition of Terms, section 5) for 30 days prior to vaccination
• Has a negative urine pregnancy test on the day of vaccination
• Agrees 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 90 days prior to the first vaccine/placebo dose (for corticosteroids, this will mean prednisone \>=5mg/day or equivalent; inhaled, intranasal and topical steroids are allowed)
• History of dengue infection or dengue illness, or history of flavivirus vaccination (e.g., yellow fever, tick-borne-encephalitis virus \[TBEV\], Japanese encephalitis, and dengue)
• 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
• Autoimmune disease or history of autoimmune disease
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine/placebo or related to a study procedure
• Major congenital defects or serious chronic illness
• History of any neurological disorders or seizures
• Diagnosed with excessive daytime sleepiness (unintended sleep episodes during the day present almost daily for at least 1 month) or narcolepsy; or history of narcolepsy in a subject's parent, sibling, or child
• Acute disease and/or fever (≥37.5°C/99.5°F oral body temperature) at the time of enrollment: note that a subject with a minor illness such as 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

Sponsors & Collaborators

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

Study Sites (2)

University of Maryland, Center for Vaccine Development,

Baltimore, Maryland, 21201, United States

Location

WRAIR, Clinical Trials Center

Silver Spring, Maryland, 20910-7500, United States

Location

Related Publications (1)

• Lin L, Lyke KE, Koren M, Jarman RG, Eckels KH, Lepine E, McArthur MA, Currier JR, Friberg H, Moris P, Keiser PB, De La Barrera R, Vaughn DW, Paris RM, Thomas SJ, Schmidt AC. Safety and Immunogenicity of an AS03B-Adjuvanted Inactivated Tetravalent Dengue Virus Vaccine Administered on Varying Schedules to Healthy U.S. Adults: A Phase 1/2 Randomized Study. Am J Trop Med Hyg. 2020 Jul;103(1):132-141. doi: 10.4269/ajtmh.19-0738. Epub 2020 Apr 23.

  PMID: 32342848 DERIVED

MeSH Terms

Conditions

Dengue

Interventions

Sodium Chloride

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)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Leyi Lin, M.D.

  USAMRMC/WRAIR

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 15, 2015
• First Posted: April 20, 2015
• Study Start: August 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: March 1, 2018
• Last Updated: September 25, 2019

Record last verified: 2019-09

Locations

US (2)