Evaluating the Safety and Immune Response to Two Doses of a Dengue Virus Vaccine Administered 12 Months Apart

NCT01782300 | Completed Phase 1 DMC

• 1 other identifier: CIR 283
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

Dengue viruses can cause dengue fever and other more severe forms of disease. This study will evaluate the safety and immune response to two doses of a dengue virus vaccine given 12 months apart in healthy adults.

Conditions

Dengue

Outcome Measures

Primary Outcomes (3)

• Frequency of vaccine-related adverse events (AEs), graded by severity

  Measured through Day 540

• Measurement of neutralizing antibody titers to DEN1, DEN2, DEN3, and DEN4 at Day 0 and 28, 56, and 90 days after each vaccination

  Monovalent, bivalent, trivalent, and tetravalent seropositivity and seroconversion rates will be determined at Day 0 and 28, 56, and 90 days after each vaccination.

  Measured at Day 0 and 28, 56, and 90 days after each vaccination

• Determination if a second dose of vaccine given at Day 360 will induce seropositivity in those vaccinees who remained seronegative to one or more DENV serotypes following the first vaccination

  Measured through Day 540

Secondary Outcomes (4)

• Frequency, quantity, and duration of viremia following each vaccination

  Measured through Day 540

• Number of vaccinees infected with DEN1, DEN2, DEN3, and DEN4

  Measured through Day 540

• Duration of the antibody response in recipients of the tetravalent vaccine

  Measured through Day 540

• Greater than or equal to 4-fold rise in serum neutralizing antibody titer by Day 450 compared with Day 360

  Measured at Day 450

Study Arms (2)

TV003 Vaccine

EXPERIMENTAL

Participants will receive an injection of the TV003 vaccine at study entry and Day 360.

Biological: TV003 Vaccine

Placebo Vaccine

PLACEBO COMPARATOR

Participants will receive an injection of the placebo vaccine at study entry and Day 360.

Biological: Placebo Vaccine

Interventions

TV003 Vaccine BIOLOGICAL

TV003 will contain an admixture of the following monovalent dengue vaccines: 10\^3 PFU of rDEN1Δ30, 10\^3 PFU of rDEN2/4Δ30(ME), 10\^3 PFU of rDEN3Δ30/31-7164, and 10\^3 PFU of rDEN4Δ30. TV003 vaccine will be administered by subcutaneous injection in participants' deltoid region of the upper arm.

TV003 Vaccine

Placebo Vaccine BIOLOGICAL

Placebo vaccine will be administered by subcutaneous injection in participants' deltoid region of the upper arm.

Placebo Vaccine

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 post-second vaccination
• Willingness to participate in the study as evidenced by signing the informed consent document
• Female participants of childbearing potential willing to use effective contraception for the duration of the trial. More information on this criterion can be found in the protocol.

You may not qualify if:

• Currently pregnant, as determined by positive beta-human choriogonadotropin (HCG) test, or breastfeeding
• 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 this protocol
• Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant 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 that 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 42 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 greater than or equal to 14 days.
• 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, 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 (2)

• Durbin AP, Kirkpatrick BD, Pierce KK, Elwood D, Larsson CJ, Lindow JC, Tibery C, Sabundayo BP, Shaffer D, Talaat KR, Hynes NA, Wanionek K, Carmolli MP, Luke CJ, Murphy BR, Subbarao K, Whitehead SS. A single dose of any of four different live attenuated tetravalent dengue vaccines is safe and immunogenic in flavivirus-naive adults: a randomized, double-blind clinical trial. J Infect Dis. 2013 Mar 15;207(6):957-65. doi: 10.1093/infdis/jis936. Epub 2013 Jan 17.

  PMID: 23329850 BACKGROUND

• Durbin AP, Kirkpatrick BD, Pierce KK, Carmolli MP, Tibery CM, Grier PL, Hynes N, Opert K, Jarvis AP, Sabundayo BP, McElvany BD, Sendra EA, Larsson CJ, Jo M, Lovchik JM, Luke CJ, Walsh MC, Fraser EA, Subbarao K, Whitehead SS. A 12-Month-Interval Dosing Study in Adults Indicates That a Single Dose of the National Institute of Allergy and Infectious Diseases Tetravalent Dengue Vaccine Induces a Robust Neutralizing Antibody Response. J Infect Dis. 2016 Sep 15;214(6):832-5. doi: 10.1093/infdis/jiw067. Epub 2016 Feb 16.

  PMID: 26908742 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

Study Design

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

Study Record Dates

• First Submitted: January 30, 2013
• First Posted: February 1, 2013
• Study Start: January 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: September 1, 2016
• Last Updated: June 14, 2017

Record last verified: 2017-06

Locations

US (2)