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

December 13, 2010 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Phase 1 Study of the Safety and Immunogenicity of rDEN3/4delta30(ME), a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 3

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Actual)

58

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
    • Maryland
      • Baltimore, Maryland, United States, 21205
        • Center for Immunization Research

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

No

Genders Eligible for Study

All

Description

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

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
Experimental: 1
One subcutaneous vaccination with rDEN3/4delta30(ME) vaccine (10^3 PFU dose) into the deltoid region of either arm.
Biological: rDEN3/4delta30(ME)
Live attenuated rDEN3/4delta30(ME) vaccine (one of three doses)
Experimental: 2
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.
Biological: rDEN3/4delta30(ME)
Live attenuated rDEN3/4delta30(ME) vaccine (one of three doses)
Experimental: 3
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.
Biological: rDEN3/4delta30(ME)
Live attenuated rDEN3/4delta30(ME) vaccine (one of three doses)
Placebo Comparator: 4
One subcutaneous vaccination with placebo into the deltoid region of either arm.
Biological: Placebo
Placebo for rDEN3/4delta30(ME)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety, as defined by frequency of vaccine-related adverse events, as classified by both intensity and severity through active and passive surveillance
Time Frame: Throughout study
Throughout study
Immunogenicity, as determined by anti-DEN3 neutralizing antibody measured on Days 0, 21, 28, 42, and 180
Time Frame: Throughout study
Throughout study

Secondary Outcome Measures

Outcome Measure
Time Frame
Assess the frequency, quantity, and duration of viremia in each dose cohort studied
Time Frame: Throughout study
Throughout study
Determine the number of vaccinees infected with rDEN3/4delta30(ME)
Time Frame: Throughout study
Throughout study
Determine cellular targets of vaccine infection, including peripheral blood mononuclear cells (PBMCs) and skin from participants who are willing to undergo skin biopsy
Time Frame: Throughout study
Throughout study
Compare the infectivity rates, safety, and immunogenicity between dose groups
Time Frame: At study completion
At study completion
Evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy
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

October 1, 2006

Primary Completion (Actual)

September 1, 2008

Study Completion (Actual)

September 1, 2008

Study Registration Dates

First Submitted

September 12, 2006

First Submitted That Met QC Criteria

September 12, 2006

First Posted (Estimate)

September 13, 2006

Study Record Updates

Last Update Posted (Estimate)

December 14, 2010

Last Update Submitted That Met QC Criteria

December 13, 2010

Last Verified

December 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CIR 228
  • WIRB Protocol Number 20061667

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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