NCT03416036

Brief Summary

The purpose of this study is to evaluate the ability of a single dose of a live attenuated recombinant tetravalent dengue vaccine (TetraVax-DV-TV003, referred to as TV003) to protect against infection with a controlled human infection strain of either DENV-2 (rDEN2Δ30-7169) or DENV-3 (rDEN3Δ30) in adults 18 to 50 years of age with no history of previous flavivirus infection.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
64

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Nov 2017

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 28, 2017

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

January 24, 2018

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 30, 2018

Completed
12 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 17, 2019

Completed
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

June 4, 2019

Completed
Last Updated

January 18, 2020

Status Verified

January 1, 2020

Enrollment Period

1.1 years

First QC Date

January 24, 2018

Last Update Submit

January 15, 2020

Conditions

Dengue

Outcome Measures

Primary Outcomes (5)

  • Frequency of rDEN2Δ30-7160 viremia

    Based on statistical analysis of laboratory evaluations

    Measured through Month 1

  • Frequency of rDEN3Δ30 viremia

    Based on statistical analysis of laboratory evaluations

    Measured through Month 1

  • Occurrence of solicited local and general adverse events (AEs)

    Evaluated using the Adverse Event Grading Table in the study protocol

    Measured through Day 56

  • Occurrence of unsolicited AEs

    Evaluated using the Adverse Event Grading Table in the study protocol

    Measured through Day 56

  • Occurrence of serious adverse events (SAEs)

    Evaluated using the Adverse Event Grading Table in the study protocol

    Measured through Day 208

Secondary Outcomes (3)

  • Frequency of viremia after vaccination with TV003

    Measured through Day 208

  • Number of TV003 recipients infected with vaccine virus DENV-1, DENV-2, DENV-3, and DENV-4

    Measured through Day 208

  • Serum plaque reduction neutralization titer 50% (PRNT50) to DENV-1, DENV-2, DENV-3, and DENV-4 viruses

    Measured through Day 180

Study Arms (4)

Arm 1: TV003 + rDEN2Δ30-7169

EXPERIMENTAL

Participants will receive a single dose of TV003 at study entry (Day 0) and rDEN2Δ30-7169 on Day 28.

Biological: TetraVax-DV-TV003 (TV003)Biological: rDEN2Δ30-7169 (DENV-2)

Arm 2: TV003 + rDEN3Δ30

EXPERIMENTAL

Participants will receive a single dose of TV003 at study entry (Day 0) and rDEN3Δ30 on Day 28.

Biological: TetraVax-DV-TV003 (TV003)Biological: rDEN3Δ30 (DENV-3)

Arm 3: Placebo + rDEN2Δ30-7169

PLACEBO COMPARATOR

Participants will receive placebo at study entry (Day 0) and rDEN2Δ30-7169 on Day 28.

Biological: rDEN2Δ30-7169 (DENV-2)Biological: Placebo

Arm 4: Placebo + rDEN3Δ30

PLACEBO COMPARATOR

Participants will receive placebo at study entry (Day 0) and rDEN3Δ30 on Day 28.

Biological: rDEN3Δ30 (DENV-3)Biological: Placebo

Interventions

TetraVax-DV-TV003 (TV003)BIOLOGICAL

TV003 contains 10\^3.3 plaque-forming units (PFU)/mL of rDEN1Δ30, 10\^3.3 PFU/mL of rDEN2/4Δ30(ME), 10\^3.3 PFU/mL of rDEN3Δ30/31-7164, and 10\^3.3 PFU/mL of rDEN4Δ30. Administered by subcutaneous injection in the deltoid region of the upper arm

Arm 1: TV003 + rDEN2Δ30-7169Arm 2: TV003 + rDEN3Δ30
rDEN2Δ30-7169 (DENV-2)BIOLOGICAL

Administered at a dose of 10\^3 PFU by subcutaneous injection in the deltoid region of the upper arm

Arm 1: TV003 + rDEN2Δ30-7169Arm 3: Placebo + rDEN2Δ30-7169
rDEN3Δ30 (DENV-3)BIOLOGICAL

Administered at a dose of 10\^3 PFU by subcutaneous injection in the deltoid region of the upper arm

Arm 2: TV003 + rDEN3Δ30Arm 4: Placebo + rDEN3Δ30
PlaceboBIOLOGICAL

Administered by subcutaneous injection in the deltoid region of the upper arm

Arm 3: Placebo + rDEN2Δ30-7169Arm 4: Placebo + rDEN3Δ30

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • Adult male or female between 18 and 50 years of age, inclusive.
  • Good general health as determined by physical examination, laboratory screening, and review of medical history.
  • Available for the duration of the study, which is approximately 28 weeks.
  • Willingness to participate in the study as evidenced by signing the informed consent document.
  • Females only: Female subjects of childbearing potential should be willing to use effective contraception and have no plans to undergo IVF (in vitro fertilization) during participation in the trial. Reliable methods of contraception include hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, intrauterine device, and abstinence (greater than or equal to 6 months since last sexual encounter with a male). All female subjects will be considered as having childbearing potential, except for those who have had a hysterectomy, tubal ligation, or tubal coil (at least 3 months prior to vaccination), or are considered to be post-menopausal, as documented by at least 1 year since last menstrual period.

You may not qualify if:

  • Females only: Currently pregnant, as determined by positive β-human choriogonadotropin (HCG) test, or breast-feeding.
  • Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease based on history, physical examination, and/or laboratory studies.
  • Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the subject's ability to understand and cooperate with the requirements of the study protocol.
  • Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in this protocol.
  • Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, or would render the subject unable to comply with the protocol.
  • Any significant alcohol or drug abuse in the past 12 months that has caused medical, occupational, or family problems, as indicated by subject history.
  • History of a severe allergic reaction or anaphylaxis.
  • Severe asthma (emergency room visit or hospitalization within the last 6 months).
  • HIV infection, as indicated by screening and confirmatory assays.
  • Hepatitis C virus (HCV) infection, as indicated by screening and confirmatory assays.
  • Hepatitis B virus (HBV) infection, as indicated by hepatitis B surface antigen (HBsAg) screening.
  • Any known immunodeficiency syndrome.
  • Current use of anticoagulant medications (this does not include anti-platelet medication such as aspirin or non-steroidal anti-inflammatory medications).
  • Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 28 days prior to or following vaccination. An immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg of a prednisone equivalent per day for greater than or equal to 14 days.
  • Receipt of a live vaccine within 28 days or a killed vaccine within 14 days prior to vaccination, or anticipated receipt of any vaccine during the 28 days following vaccination.
  • +34 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health

Baltimore, Maryland, 21205, United States

Location

Vaccine Testing Center, University of Vermont

Burlington, Vermont, 05405, United States

Location

Related Publications (1)

  • Kirkpatrick BD, Whitehead SS, Pierce KK, Tibery CM, Grier PL, Hynes NA, Larsson CJ, Sabundayo BP, Talaat KR, Janiak A, Carmolli MP, Luke CJ, Diehl SA, Durbin AP. The live attenuated dengue vaccine TV003 elicits complete protection against dengue in a human challenge model. Sci Transl Med. 2016 Mar 16;8(330):330ra36. doi: 10.1126/scitranslmed.aaf1517. Epub 2016 Mar 16.

    PMID: 27089205BACKGROUND

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne DiseasesVector Borne DiseasesInfectionsArbovirus InfectionsVirus DiseasesFlavivirus InfectionsFlaviviridae InfectionsRNA Virus InfectionsHemorrhagic Fevers, Viral

Study Officials

  • Anna Durbin, MD

    Johns Hopkins Bloomberg School of Public Health

    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
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 24, 2018

First Posted

January 30, 2018

Study Start

November 28, 2017

Primary Completion

January 17, 2019

Study Completion

June 4, 2019

Last Updated

January 18, 2020

Record last verified: 2020-01

Locations

US(2)