Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-4995) in Healthy Adults

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 1

Conditions: Dengue

Treatments: Biological: Placebo; Biological: rDEN4delta30-4995

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00322946

WIRB Protocol Number 20061807

CIR 221

Details and patient eligibility

About

Dengue fever, which is caused by dengue viruses, is a major health problem in tropical and subtropical regions of the world. The purpose of this study is to evaluate the safety and immune response to the dengue vaccine DEN4delta30-4995 in healthy adults.

Full description

Dengue viruses account for more than 50 million cases of dengue fever and a half million cases of the more severe disease, dengue hemorrhagic fever/dengue shock syndrome. Infection with dengue viruses is the leading cause of hospitalization and death in children in at least eight Asian countries. The goal of producing a vaccine against dengue fever is to induce a long-lived antibody response against all four dengue serotypes. The rDEN4delta30-4995 vaccine candidate is a live attenuated recombinant virus derived from rDEN4delta30 for protection against dengue virus serotype 4. The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of rDEN4delta30-4995 in healthy adults.

This study will last 180 days (6 months). Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30 or placebo at study entry. Participants in Cohort 2 will be randomly assigned to receive a lower dose of rDEN4delta30 or placebo. Participants in Cohort 3 will be randomly assigned to receive the lowest dose of rDEN4delta30 or placebo. Cohorts 2 and 3 will begin after a safety review of all participants in the previous cohort.

After initial vaccination, participants in Cohort 1 will be followed every other day for the first 16 days of the study, monitoring their temperature three times a day through Day 16 and recording these measurements in a diary. After Day 16, study visits will occur on Days 21, 28, 42, and 180 and will include a physical exam and blood collection. Some participants will also be asked to undergo a skin biopsy or additional blood collection at selected visits.

Enrollment: 84 estimated patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adult males and non-pregnant females between 18 and 50 years of age
• Good general health
• Available for the duration of the study
• Willing to use acceptable methods of contraception for the duration of the study

Exclusion criteria

• Significant neurologic, cardiac, 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
• Severe asthma
• HIV-1 serotype infected
• Hepatitis C virus (HCV) infected
• Hepatitis B surface antigen positive
• Immunodeficiency syndrome
• Use of corticosteroids or immunosuppressive medications within 2 weeks prior to study entry. Individuals 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
• Prior receipt of yellow fever or dengue vaccine (licensed or experimental)
• 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 affect participation in the study
• Pregnant or breastfeeding

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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84 participants in 4 patient groups, including a placebo group

1

Experimental group

Description:

One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10\^5 PFU dose) into the deltoid region of either arm.

Treatment:

Biological: rDEN4delta30-4995

2

Experimental group

Description:

One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10\^3 PFU dose) into the deltoid region of either arm. This arm will enroll after Arm 1.

Treatment:

Biological: rDEN4delta30-4995

3

Experimental group

Description:

One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10\^1 PFU dose) into the deltoid region of either arm. This arm will enroll after Arms 1 and 2.

Treatment:

Biological: rDEN4delta30-4995

4

Placebo Comparator group

Description:

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

Treatment:

Biological: Placebo