Evaluation of the Safety and Efficacy of a Single Dose of a Dengue Vaccine (TV005) in Healthy Adults

NCT02317900 | Completed Phase 1 DMC

• 1 other identifier: CIR 299
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 2

Brief Summary

Dengue viruses are widespread in most tropical and subtropical regions of the world. This study will evaluate the safety and protective efficacy of a dengue vaccine (called TV005) against viremia and rash induced by a DENV-2 vaccine virus (called rDEN2∆30-7169) in healthy adults.

Conditions

Dengue

Outcome Measures

Primary Outcomes (2)

• Frequency of viremia in participants administered 10^3 PFU of rDEN2∆30-7169 at Study Day 180

  The incidence, magnitude, and duration of rDEN2∆30-7169 viremia following administration of rDEN2∆30-7169 at Study Day 180 in participants who received TV005 on Study Day 0 will be compared to those who received placebo on Study Day 0.

  Measured through Day 360

• Proportion of participants who received TV005 & develop rash and/or neutropenia following administration of rDEN2∆30-7169 compared to proportion of participants who received placebo & developed rash and/or neutropenia following receipt of rDEN2∆30-7169

  Measured through Day 360

Secondary Outcomes (9)

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

  Measured through Day 28 after each vaccination

• Frequency of virus-related AEs, graded by severity, following primary inoculation (inoculation of those participants who received placebo at Study Day 0)

  Measured through Day 28 after each vaccination

• Frequency of viremia of rDEN1∆30, rDEN2/4∆30(ME), rDEN3∆30/31, and rDEN4∆30 following TV005 vaccination

  Measured through Day 16

• Number of TV005 vaccinees infected with DENV-1, DENV-2, DENV-3, and DENV-4

  Measured through Day 360

• Evaluation of the immunogenicity of TV005, as assessed by PRNT50 to DENV-1, DENV-2, DENV-3, and DENV-4 at 28, 56, and 90 days after TV005 vaccination

  Measured through Day 360

Study Arms (2)

TV005 and rDEN2∆30-7169

EXPERIMENTAL

Participants will receive one injection of TV005 at study entry (Day 0). On Day 180, participants will receive one injection of rDEN2∆30-7169.

Biological: TV005; Biological: rDEN2∆30-7169

Placebo and rDEN2∆30-7169

PLACEBO COMPARATOR

Participants will receive one injection of placebo at study entry (Day 0). On Day 180, participants will receive one injection of rDEN2∆30-7169.

Biological: Placebo; Biological: rDEN2∆30-7169

Interventions

TV005 BIOLOGICAL

TV005 is a live attenuated recombinant tetravalent dengue virus vaccine. It will be administered as a 0.5 mL dose containing 10\^3 plaque forming units (PFUs) of each component (10\^3.3 PFUs/mL of rDEN1∆30, 10\^4.3 PFU/mL of rDEN2/4∆30(ME), 10\^3.3 PFU/mL of rDEN3∆30/31-7164 and 10\^3.3 PFU/mL of rDEN4∆30). It will be delivered by subcutaneous injection in the deltoid region of the upper arm.

TV005 and rDEN2∆30-7169

Placebo BIOLOGICAL

The placebo vaccine will be administered as a 0.5 mL dose delivered by subcutaneous injection in the deltoid region of the upper arm.

Placebo and rDEN2∆30-7169

rDEN2∆30-7169 BIOLOGICAL

rDEN2∆30-7169 is a live recombinant attenuated DENV-2 candidate vaccine virus. It 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 and rDEN2∆30-7169; TV005 and rDEN2∆30-7169

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (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, approximately 26 weeks post-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 longer since last sexual encounter). All female participants will be considered having childbearing 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, 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 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 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 School of Public Health

Baltimore, Maryland, 21205, United States

Location

University of Vermont Vaccine Testing Center

Burlington, Vermont, 05405, United States

Location

Related Publications (1)

• Pierce KK, Durbin AP, Walsh MR, Carmolli M, Sabundayo BP, Dickson DM, Diehl SA, Whitehead SS, Kirkpatrick BD. TV005 dengue vaccine protects against dengue serotypes 2 and 3 in two controlled human infection studies. J Clin Invest. 2024 Feb 1;134(3):e173328. doi: 10.1172/JCI173328.

  PMID: 37971871 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: 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 15, 2014
• First Posted: December 17, 2014
• Study Start: December 1, 2014
• Primary Completion: November 1, 2016
• Last Updated: February 1, 2017

Record last verified: 2017-01

Locations

US (2)