Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3/4delta30[ME]) in Healthy Adults

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 1

Conditions: Dengue

Treatments: Biological: rDEN3/4delta30(ME); Biological: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00375726

CIR 228

WIRB Protocol Number 20061667

Details and patient eligibility

About

Dengue fever, caused by dengue viruses, is a major health problem in the tropical and subtropical regions of the world. The purpose of this study is to test the safety of and immune response to a new dengue virus vaccine in healthy adults.

Full description

Dengue viruses, which cause dengue fever and dengue shock syndrome, are a major cause of morbidity and mortality in several of the world's tropical and subtropical regions. The rDEN3/4delta30(ME) vaccine is a live attenuated dengue virus vaccine that may be protective against dengue virus serotype 3 (DEN3). The purpose of this study is to evaluate the safety and immunogenicity of the rDEN3/4delta30(ME) vaccine in healthy adults.

This study will last 40 weeks. Participants will be randomly assigned to receive one of three doses of rDEN3/4delta30(ME) or placebo. Participants in Group 1 will receive the middle dose of rDEN3/4delta30(ME) or placebo at study entry. Group 2a will begin enrollment after the immunogenicity review of all participants in Group 1. Participants in Group 2a will receive the highest dose of rDEN4delta30(ME) or placebo at study entry. Group 2b will begin enrollment after the immunogenicity review of all participants in Group 2a. Participants in Group 2b will receive the lowest dose of rDEN4delta30(ME) or placebo.

After vaccination, participants in all groups will be followed closely every other day for the first 16 days of the study. Participants will take their temperature three times a day through Day 16 and record each measurement in a diary. After Day 16, participants will have study visits on Days 21, 28, 42, and 180; a physical exam and blood collection will occur at all visits. Some participants may be asked to join a skin biopsy substudy.

Enrollment: 58 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Good general health
• Available for the duration of the study
• Willing to use acceptable forms of contraception for the duration of the study

Exclusion criteria

• Significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease
• Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study
• Significant laboratory abnormalities
• Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months prior to study entry
• History of severe allergic reaction or anaphylaxis
• Emergency room visit or hospitalization for severe asthma within 6 months prior to study entry
• HIV-1 infected
• Hepatitis C virus (HCV) infected
• Hepatitis B surface antigen positive
• Immunodeficiency syndrome
• Use of corticosteroids or immunosuppressive medications within 30 days prior to study entry. Participants using topical or nasal corticosteroids are not excluded.
• Live vaccine within 4 weeks prior to study entry
• Killed vaccine within 2 weeks prior to study entry
• Absence of spleen
• Blood products within 6 months prior to study entry
• Previous dengue virus or other flavivirus (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus) infection
• Previously received yellow fever or dengue vaccine
• Plans to travel to an area where dengue infection is common
• Received an investigational agent within 30 days prior to study entry
• Other condition that, in the opinion of the investigator, would interfere with the study
• Pregnancy or breastfeeding

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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58 participants in 4 patient groups, including a placebo group

1

Experimental group

Description:

One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10\^3 PFU dose) into the deltoid region of either arm.

Treatment:

Biological: rDEN3/4delta30(ME)

2

Experimental group

Description:

One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10\^5 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1.

Treatment:

Biological: rDEN3/4delta30(ME)

3

Experimental group

Description:

One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10\^1 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the immunological response of Arm 1.

Treatment:

Biological: rDEN3/4delta30(ME)

4

Placebo Comparator group

Description:

One subcutaneous vaccination with placebo into the deltoid region of either arm.

Treatment:

Biological: Placebo