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

Primary Purpose

Dengue

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
TDENV-PIV with AS03B adjuvant. Placebo: 0.9% Sodium Chloride Solution.
Sponsored by
U.S. Army Medical Research and Development Command
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Dengue

Eligibility Criteria

20 Years - 49 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. Subjects must be able to provide written informed consent.
  2. Subjects must be healthy as established by medical history and clinical examination at study entry
  3. 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.)
  4. 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.
  5. Male or non-pregnant, non-breastfeeding female between 20 and 49 years of age (inclusive) at the time of consent
  6. 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).
  7. 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.

Exclusion Criteria:

  1. 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
  2. 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)
  3. Planned administration or administration of a vaccine/product not planned in the study protocol during the period starting 30 days prior to the first dose of vaccine/placebo until 30 days after the last dose of study vaccine/placebo (routine influenza vaccination will be allowed as long as it is not administered within 14 days of the vaccine/placebo, and will not lead to study exclusion although it should be reported to the PI)
  4. 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)
  5. Planned administration of any flavivirus vaccine for the entire study duration
  6. 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)
  7. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required)
  8. Family history of congenital or hereditary immunodeficiency
  9. Autoimmune disease or history of autoimmune disease
  10. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine/placebo or related to a study procedure
  11. Major congenital defects or serious chronic illness
  12. History of any neurological disorders or seizures
  13. 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
  14. 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
  15. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests
  16. 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
  17. Recent history of chronic alcohol consumption (more than 2 drinks per day and/or drug abuse (based on subject reported history)
  18. Pregnant or breastfeeding female or female currently planning to become pregnant or planning to discontinue adequate contraception
  19. A planned move to a location that will prohibit participating in the trial until Study End for the participant
  20. Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.
  21. Subject seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)
  22. Safety laboratory test results at screening that are deemed clinically significant or more than Grade 1 deviation from normal

Sites / Locations

  • University of Maryland, Center for Vaccine Development,
  • WRAIR, Clinical Trials Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

TDENV-PIV (0-1)

TDENV-PIV (0-1-6)

TDENV-PIV (0-3)

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Number of solicited local adverse events related to product
Intensity of solicited local adverse events related to product
Number of unsolicited adverse events related to product
Intensity of unsolicited adverse events related to product
Number of Grade 2 laboratory abnormalities
Number of Grade 3 laboratory abnormalities
Number of serious adverse events from day 0 through 28 days after the last dose
Number of potential immune-mediated diseases from Day 0 through 28 days after the last dose
Neutralizing antibody titers to each DENV type
Number of general adverse events related to product
Intensity of solicited general adverse events related to product
Number of medically attended AEs related to product

Secondary Outcome Measures

Number of potential immune-mediated diseases from post Month 7 to Study End
Number of serious adverse events related to product
Neutralizing antibody titers to each DENV type
Seropositivity status for each DENV type
Number of medically attended AEs from post Month 7 to Study End
Neutralizing antibody titers to each DENV type for the TDENV-PIV (0-1-6) group
Neutralizing antibody titers to each DENV type
Neutralizing antibody titers to each DENV type
Neutralizing antibody titers to each DENV type
Neutralizing antibody titers to each DENV type
Seropositivity status for each DENV type for the TDENV-PIV (0-1-6) group
Seropositivity status for each DENV type for the TDENV-PIV (0-1-6) group
Seropositivity status for each DENV type
Seropositivity status for each DENV type
Seropositivity status for each DENV type
Seropositivity status for each DENV type

Full Information

First Posted
April 15, 2015
Last Updated
September 24, 2019
Sponsor
U.S. Army Medical Research and Development Command
Collaborators
Walter Reed Army Institute of Research (WRAIR), GlaxoSmithKline
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1. Study Identification

Unique Protocol Identification Number
NCT02421367
Brief Title
Study of Varying Injection Schedules of TDENV-PIV Vaccine With AS03B Adjuvant and Placebo in Healthy US Adults
Official Title
A Phase 1/2, Randomized, Observer-blind Study of Varying Injection Schedules of a Tetravalent Dengue Virus Purified Inactivated Vaccine (TDENV-PIV) With AS03B Adjuvant and Placebo in Healthy Adults in the US
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
August 2015 (Actual)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
March 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
U.S. Army Medical Research and Development Command
Collaborators
Walter Reed Army Institute of Research (WRAIR), GlaxoSmithKline

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
140 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TDENV-PIV (0-1)
Arm Type
Experimental
Arm Description
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.
Arm Title
TDENV-PIV (0-1-6)
Arm Type
Experimental
Arm Description
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.
Arm Title
TDENV-PIV (0-3)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
TDENV-PIV with AS03B adjuvant. Placebo: 0.9% Sodium Chloride Solution.
Intervention Description
Tetravalent dengue virus purified inactivated vaccine (1 µg/virus type)
Primary Outcome Measure Information:
Title
Number of solicited local adverse events related to product
Time Frame
7-day follow-up period after each dose
Title
Intensity of solicited local adverse events related to product
Time Frame
7-day follow-up period after each dose
Title
Number of unsolicited adverse events related to product
Time Frame
28-day follow-up period after each dose
Title
Intensity of unsolicited adverse events related to product
Time Frame
28-day follow-up period after each dose
Title
Number of Grade 2 laboratory abnormalities
Time Frame
7-day follow-up period after each dose
Title
Number of Grade 3 laboratory abnormalities
Time Frame
7-day follow-up period after each dose
Title
Number of serious adverse events from day 0 through 28 days after the last dose
Time Frame
7 months after first dose
Title
Number of potential immune-mediated diseases from Day 0 through 28 days after the last dose
Time Frame
7 months after first dose
Title
Neutralizing antibody titers to each DENV type
Time Frame
Day 0 and 28 days after the second and third doses of TDENV-PIV
Title
Number of general adverse events related to product
Time Frame
7-day follow-up period after each dose
Title
Intensity of solicited general adverse events related to product
Time Frame
7-day follow-up period after each dose
Title
Number of medically attended AEs related to product
Time Frame
Day 0 through 28 days after the last dose
Secondary Outcome Measure Information:
Title
Number of potential immune-mediated diseases from post Month 7 to Study End
Time Frame
7 months after first dose to the end of study
Title
Number of serious adverse events related to product
Time Frame
7 months after first dose to the end of study
Title
Neutralizing antibody titers to each DENV type
Time Frame
56 days after the second dose of active vaccine
Title
Seropositivity status for each DENV type
Time Frame
28 days after the second dose of active vaccine for all groups
Title
Number of medically attended AEs from post Month 7 to Study End
Time Frame
7 months after first dose to the end of study
Title
Neutralizing antibody titers to each DENV type for the TDENV-PIV (0-1-6) group
Time Frame
56 days after the third dose of active vaccine
Title
Neutralizing antibody titers to each DENV type
Time Frame
4 months after the last dose of active vaccine
Title
Neutralizing antibody titers to each DENV type
Time Frame
6 months after the last dose of active vaccine
Title
Neutralizing antibody titers to each DENV type
Time Frame
9 months after the last dose of active vaccine
Title
Neutralizing antibody titers to each DENV type
Time Frame
12 months after the last dose of active vaccine
Title
Seropositivity status for each DENV type for the TDENV-PIV (0-1-6) group
Time Frame
28 days after the third dose of active vaccine
Title
Seropositivity status for each DENV type for the TDENV-PIV (0-1-6) group
Time Frame
56 days after the third dose of active vaccine
Title
Seropositivity status for each DENV type
Time Frame
4 months after the last dose of active vaccine for all groups
Title
Seropositivity status for each DENV type
Time Frame
6 months after the last dose of active vaccine for all groups
Title
Seropositivity status for each DENV type
Time Frame
9 months after the last dose of active vaccine for all groups
Title
Seropositivity status for each DENV type
Time Frame
12 months after the last dose of active vaccine for all groups

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
49 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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. 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 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) Planned administration or administration of a vaccine/product not planned in the study protocol during the period starting 30 days prior to the first dose of vaccine/placebo until 30 days after the last dose of study vaccine/placebo (routine influenza vaccination will be allowed as long as it is not administered within 14 days of the vaccine/placebo, and will not lead to study exclusion although it should be reported to the PI) 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 Recent history of chronic alcohol consumption (more than 2 drinks per day and/or drug abuse (based on subject reported history) Pregnant or breastfeeding female or female currently planning to become pregnant or planning to discontinue adequate contraception 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 at screening that are deemed clinically significant or more than Grade 1 deviation from normal
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leyi Lin, M.D.
Organizational Affiliation
USAMRMC/WRAIR
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Maryland, Center for Vaccine Development,
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
WRAIR, Clinical Trials Center
City
Silver Spring
State/Province
Maryland
ZIP/Postal Code
20910-7500
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
32342848
Citation
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.
Results Reference
derived

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

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