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

August 5, 2009 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-4995, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 4

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Anticipated)

84

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37232-2581
        • Vanderbilt University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 4
One subcutaneous vaccination with placebo into the deltoid region of either arm.
Biological: Placebo
Placebo for rDEN4delta30-4995
Experimental: 1
One subcutaneous vaccination with rDEN4delta30-4995 vaccine (10^5 PFU dose) into the deltoid region of either arm.
Biological: rDEN4delta30-4995
Live attenuated rDEN4delta30-4995 vaccine (one of three doses)
Experimental: 2
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.
Biological: rDEN4delta30-4995
Live attenuated rDEN4delta30-4995 vaccine (one of three doses)
Experimental: 3
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.
Biological: rDEN4delta30-4995
Live attenuated rDEN4delta30-4995 vaccine (one of three doses)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Frequency of vaccine-related adverse events, graded by severity for each dose
Time Frame: Throughout study
Throughout study
Immunogenicity of the rDEN4delta30-4995 vaccine against DEN4 virus by measurement of plaque reduction neutralization titers (PRNT)
Time Frame: At Days 28 and 42
At Days 28 and 42

Secondary Outcome Measures

Outcome Measure
Time Frame
Durability of antibody responses to DEN4 virus
Time Frame: At Month 6
At Month 6
Frequency, quantity, and duration of viremia in each dose cohort studied based on the mean peak viremia, mean day onset of viremia, and mean duration of viremia of each dose cohort
Time Frame: Throughout study
Throughout study
Number of vaccinees infected with the rDEN4delta30-4995 chimeric vaccine
Time Frame: Throughout study
Throughout study

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Johns Hopkins Bloomberg School of Public Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Primary Completion (Actual)

August 1, 2009

Study Registration Dates

First Submitted

May 4, 2006

First Submitted That Met QC Criteria

May 4, 2006

First Posted (Estimate)

May 8, 2006

Study Record Updates

Last Update Posted (Estimate)

August 7, 2009

Last Update Submitted That Met QC Criteria

August 5, 2009

Last Verified

November 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIR 221
  • WIRB Protocol Number 20061807

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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