Safety of and Immune Response of a 2-dose Regimen of rDEN1delta30 Dengue Virus Vaccine

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 1

Conditions: Dengue

Treatments: Biological: Placebo; Biological: rDEN1delta30

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00473135

CIR 229

WIRB Protocol Number 20070718

Details and patient eligibility

About

Dengue fever, 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 of and immune response to a 2-dose regimen of a new monovalent dengue virus vaccine. This study will test the dengue virus vaccine DEN1delta30 in healthy adults.

Full description

Dengue viruses account for more than 50 million cases of dengue fever and one half million cases annually of dengue hemorrhagic fever/shock syndrome. Dengue virus infections can cause illness ranging from mild, self-limited febrile illness to life threatening diseases. The goal of dengue vaccine development is to induce a long-lived antibody response against all four dengue serotypes. The rDEN1delta30 vaccine is a live attenuated dengue virus vaccine that may be protective against dengue serotype 1 (DEN1). The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of a 2-dose regimen of rDEN1delta30 dengue virus vaccine. The regimen will differ in when the second booster shot of the vaccine is given.

This study will last 162 days (about 23 weeks) for those participants in Cohort 1, and 222 days (about 32 weeks) for those in Cohort 2. Participants in Cohort 1 will be randomly assigned to receive rDEN1delta30 vaccine or placebo on Study Day 0 and Study Day 120. Participants in Cohort 2 will be randomly assigned to receive rDEN1delta30 vaccine or placebo on Study Day 0 and Study Day 180.

There will be a total of 25 visits for each cohort. For both cohorts, the first and second vaccination days will include a physical exam and blood and urine collection, vital signs measurements, and receipt of the vaccine. A 30 minute observation period will follow vaccination. Participants will take their temperature at home three times a day for the first 16 days and report it in a diary. At all other study visits, vital signs measurements, a physical exam, and blood and/or urine collection will occur. At selected study visits, participants will turn in their diary cards.

Some participants may be asked to join an optional skin biopsy substudy.

Enrollment: 60 estimated 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 (23 weeks for Cohort 1 and 32 weeks for Cohort 2)
• Willing to use acceptable forms of contraception for the duration of the study

Exclusion criteria

• Clinically 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
• Severe asthma
• HIV-1 infected
• Hepatitis C virus (HCV) infected
• Hepatitis B surface antigen positive
• Known immunodeficiency syndrome
• Use of corticosteroids or immunosuppressive medications within 30 days prior to study entry. Individuals using topical or nasal corticosteroids are not excluded.
• Previous receipt of a live vaccine within 4 weeks prior to study entry
• Previous receipt of a killed vaccine within 2 weeks prior to study entry
• Absence of spleen
• Previous receipt of blood products within 6 months prior to study entry
• Previous receipt of dengue virus or other flavivirus (e.g., yellow fever virus, St.Louis encephalitis, West Nile virus) infection
• Previous receipt of yellow fever or dengue vaccine
• Plans to travel to an area where dengue infection is common
• Previous receipt of any 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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60 participants in 3 patient groups, including a placebo group

1

Experimental group

Description:

Two subcutaneous vaccinations with rDEN1delta30 into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on Day 120.

Treatment:

Biological: rDEN1delta30

2

Experimental group

Description:

Two subcutaneous vaccinations with rDEN1delta30 into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on Day 180.

Treatment:

Biological: rDEN1delta30

3

Placebo Comparator group

Description:

Two subcutaneous vaccinations with placebo into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on either Day 120 or 180, depending on arm assignment.

Treatment:

Biological: Placebo