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

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase

Completed

Phase 1

Conditions

Dengue

Treatments

Biological: Placebo Vaccine

Biological: TV003 Vaccine

Study type

Interventional

Funder types

NIH

Identifiers

NCT01782300

CIR 283

Details and patient eligibility

About

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.

Full description

Dengue viruses are a major health concern, particularly in the tropical and subtropical regions of the world. The World Health Organization (WHO) has made the development of a dengue vaccine a top priority. There are four types of dengue viruses (DEN1, DEN2, DEN3, and DEN4), each of which can cause various illnesses, including dengue fever, or the more severe disease, dengue hemorrhagic fever/shock syndrome (DHF/DSS). This study will evaluate the safety and immune response to two doses of a dengue virus vaccine (TV003) when administered 12 months apart in healthy adults. The study will also evaluate whether the candidate vaccine may protect against all four types of dengue viruses.

Participants will be randomly assigned to receive the TV003 study vaccine or placebo vaccine. At study entry, participants will undergo a blood collection and physical examination, and female participants will take a pregnancy test. Participants will then receive an injection of their assigned vaccine. They will take their temperature three times a day for 16 days after each vaccination and record the results on a diary card, which research staff will review during participants' study visits. Additional study visits will occur on Days 3, 10, 14, 21, 28, 56, 90, 180, 270, and 330. All study visits will include blood collection and a physical examination; select visits will include a pregnancy test for female participants. At a study visit on Day 360, all participants will receive an injection of the same vaccine they received at study entry. Additional study visits will occur on Days 363, 370, 374, 381, 388, 416, 450, and 540, and will include the same study procedures as previously performed.

Enrollment

48 estimated patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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
Asplenia
Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination
Anticipated receipt of any investigational agent in the 28 days before or after vaccination
Has definite plans to travel to a dengue endemic area during the study
Refusal to allow storage of specimens for future research

Inclusion Criteria for Second Dose of Vaccine:

Good general health as determined by physical examination and review of medical history
Available for the duration of the study, approximately 26 weeks after second dose
Ongoing willingness to continue to participate in the study
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.

Exclusion Criteria for Second Dose of Vaccine:

Anaphylaxis or angioedema following the first dose of vaccine
Currently pregnant (as determined by positive beta-HCG test), breastfeeding, or, for those of childbearing potential, no longer using a reliable method of contraception
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
Day 330 laboratory values of Grade 1 or above for serum ALT and 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
HCV infection, by screening and confirmatory assays
HBV infection, by 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
Asplenia
Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination
Anticipated receipt of any other investigational agent in the 28 days before or after vaccination
Has definite plans to travel to a dengue endemic area during the study
Refusal to allow storage of specimens for future research

Other Treatments and Ongoing Exclusion Criteria:

The following criteria will be reviewed on Days 28, 56, and 90 following each vaccination. If any become applicable during the study, the participant will not be included in further immunogenicity evaluations, as of the exclusionary visit. The participant will, however, be encouraged to remain in the study for safety evaluations for the duration of the study.

Ongoing Exclusion Criteria:

Use of any investigational drug or investigational vaccine other than the study vaccine during the 28-day period post-vaccination
Chronic administration (greater than or equal to 14 days) of steroids (defined as prednisone equivalent of greater than or equal to 10 mg per day), immunosuppressants, or other immune-modifying drugs initiated during the 28-day period post-vaccination (topical and nasal steroids are allowed)
Receipt of a licensed vaccine during the 28-day period post-vaccination
Receipt of immunoglobulins and/or any blood products during the 28-day period post-vaccination
Pregnancy