Evaluating the Safety and Effectiveness of a Dengue Virus Vaccine in Healthy Adults

NCT02021968 | Completed Phase 1 DMC

• 1 other identifier: CIR 287
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

Dengue viruses can cause dengue illness ranging from a mild illness to life-threatening disease. The purpose of this study is to evaluate the protective effectiveness of a dengue virus vaccine in healthy adults.

Conditions

Dengue

Outcome Measures

Primary Outcomes (3)

• Protection against viremia induced by rDEN2∆30, determined by rDEN2∆20-7169 titer

  Participants will receive rDEN2∆30-7169 at Day 180. Viremia caused by rDEN2∆30-7160 will be measured through Day 196. Blood samples will be obtained from all participants on Days 180, 182, 184, 186, 188, 190, 192, 194, and 196, and the titer of rDEN2∆20-7169 will be determined.

  Measured through Day 196

• Frequency of TV003 and rDEN2∆30-7169-related adverse events (AEs), as classified by both severity and seriousness, through active and passive surveillance

  Measured through participants' last study visit on Day 360

• Dengue virus neutralizing antibody titer

  Seropositivity to each serotype will be defined as a PRNT50 of greater than or equal to 1:10 by Day 90 (TV003) and by Day 270 (rDEN2∆30-7169).

  Measured through participants' last study visit on Day 360

Other Outcomes (4)

• Frequency of viremia following TV003 vaccination

  Measured through Day 16 visit

• Quantity of viremia following TV003 vaccination

  Measured through Day 16 visit

• Duration of viremia following TV003 vaccination

  Measured through Day 16 visit

Study Arms (2)

TetraVax-DV-TV003 vaccine

EXPERIMENTAL

Participants in this arm will receive a single injection of the TetraVax-DV-TV003 vaccine on Day 0 (study entry). On Day 180, participants will receive a single injection of the attenuated rDEN2∆30-7169 virus.

Biological: TetraVax-DV-TV003; Biological: rDEN2∆30-7169

Placebo

PLACEBO COMPARATOR

Participants in this arm will receive a single injection of placebo on Day 0 (study entry). On Day 180, participants will receive a single injection of the attenuated rDEN2∆30-7169 virus.

Biological: rDEN2∆30-7169; Biological: Placebo

Interventions

TetraVax-DV-TV003 BIOLOGICAL

TetraVax-DV-TV003 is a live attenuated recombinant tetravalent dengue virus vaccine, which will be administered as a 0.5 mL dose containing 10\^3.0 plaque forming units (PFUs) each of DENV-1, DENV-2, DENV-3, and DENV-4. It will be delivered by subcutaneous injection in the deltoid region of the upper arm.

Also known as: TV003

TetraVax-DV-TV003 vaccine

rDEN2∆30-7169 BIOLOGICAL

The challenge virus, rDEN2∆30-7169, is a live recombinant attenuated DENV-2 candidate vaccine virus and will be administered as a 0.5 mL dose containing 10\^3 PFUs of rDEN2∆30-7169. It will be delivered by subcutaneous injection in the deltoid region of the upper arm.

Placebo; TetraVax-DV-TV003 vaccine

Placebo BIOLOGICAL

The placebo vaccine is the vaccine diluent 1X L-15, which will be administered as a 0.5 mL dose delivered by subcutaneous injection in the deltoid region of the upper arm.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Good general health as determined by physical examination, laboratory screening, and review of medical history
• Available for the duration of the study, approximately 26 weeks after second inoculation
• Willingness to participate in the study as evidenced by signing the informed consent document
• Females Only: Female participants of childbearing potential willing to use effective contraception. Reliable methods of contraception include: hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, intrauterine device, and abstinence (6 months or more since last sexual encounter). All female participants will be considered having child-bearing potential except for those with hysterectomy, tubal ligation, tubal coil (at least 3 months prior to vaccination), or post-menopausal status documented as at least 1 year since last menstrual period.

You may not qualify if:

• Females Only: Currently pregnant, as determined by positive beta-human choriogonadotropin (HCG) test, breast-feeding
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies
• Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant 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 the study protocol.
• Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the participant unable to comply with the protocol
• Any significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by participant history
• History of a severe allergic reaction or anaphylaxis
• Severe asthma (emergency room visit or hospitalization within the last 6 months)
• HIV infection, by screening and confirmatory assays
• Hepatitis C virus (HCV) infection, by screening and confirmatory assays
• Hepatitis B virus (HBV) infection, by hepatitis B surface antigen (HBsAg) screening
• Any known immunodeficiency syndrome
• Use of anticoagulant medications
• Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 28 days prior to or following vaccination. Immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg prednisone equivalent per day for 14 days or longer.
• Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 28 days following vaccination

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (2)

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

Baltimore, Maryland, 21205, United States

Location

University of Vermont Vaccine Testing Center

Burlington, Vermont, 05405, United States

Location

Related Publications (3)

• Hanley JP, Tu HA, Dragon JA, Dickson DM, Rio-Guerra RD, Tighe SW, Eckstrom KM, Selig N, Scarpino SV, Whitehead SS, Durbin AP, Pierce KK, Kirkpatrick BD, Rizzo DM, Frietze S, Diehl SA. Immunotranscriptomic profiling the acute and clearance phases of a human challenge dengue virus serotype 2 infection model. Nat Commun. 2021 May 24;12(1):3054. doi: 10.1038/s41467-021-22930-6.

  PMID: 34031380 DERIVED

• Nivarthi UK, Swanstrom J, Delacruz MJ, Patel B, Durbin AP, Whitehead SS, Kirkpatrick BD, Pierce KK, Diehl SA, Katzelnick L, Baric RS, de Silva AM. A tetravalent live attenuated dengue virus vaccine stimulates balanced immunity to multiple serotypes in humans. Nat Commun. 2021 Feb 17;12(1):1102. doi: 10.1038/s41467-021-21384-0.

  PMID: 33597521 DERIVED

• Larsen CP, Whitehead SS, Durbin AP. Dengue human infection models to advance dengue vaccine development. Vaccine. 2015 Dec 10;33(50):7075-82. doi: 10.1016/j.vaccine.2015.09.052. Epub 2015 Sep 28.

  PMID: 26424605 DERIVED

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

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

Study Officials

• Anna Durbin, MD

  Center for Immunization Research (CIR), Johns Hopkins School of Public Health

  PRINCIPAL INVESTIGATOR

• Beth Kirkpatrick, MD

  University of Vermont

  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: December 20, 2013
• First Posted: December 27, 2013
• Study Start: November 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: December 1, 2015
• Last Updated: December 15, 2015

Record last verified: 2015-12

Locations

US (2)