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

This study has been completed.
Sponsor:
Collaborator:
Johns Hopkins Bloomberg School of Public Health
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00322946
First received: May 4, 2006
Last updated: August 5, 2009
Last verified: November 2008
  Purpose

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.


Condition Intervention Phase
Dengue
Biological: rDEN4delta30-4995
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-4995, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 4

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Frequency of vaccine-related adverse events, graded by severity for each dose [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Immunogenicity of the rDEN4delta30-4995 vaccine against DEN4 virus by measurement of plaque reduction neutralization titers (PRNT) [ Time Frame: At Days 28 and 42 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Durability of antibody responses to DEN4 virus [ Time Frame: At Month 6 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Number of vaccinees infected with the rDEN4delta30-4995 chimeric vaccine [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment: 84
Study Start Date: January 2007
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
Placebo Comparator: 4
One subcutaneous vaccination with placebo into the deltoid region of either arm.
Biological: Placebo
Placebo for rDEN4delta30-4995

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00322946

Locations
United States, Tennessee
Vanderbilt University School of Medicine
Nashville, Tennessee, United States, 37232-2581
Sponsors and Collaborators
Johns Hopkins Bloomberg School of Public Health
Investigators
Principal Investigator: Anna Durbin, MD Center for Immunization Research (CIR), Johns Hopkins School of Public Health
  More Information

Publications:
Responsible Party: Anna Durbin, MD, Center for Immunization Research, Johns Hopkins School of Public Health
ClinicalTrials.gov Identifier: NCT00322946     History of Changes
Other Study ID Numbers: CIR 221, WIRB Protocol Number 20061807
Study First Received: May 4, 2006
Last Updated: August 5, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Dengue Fever
Dengue Vaccine
Dengue Virus
Dengue Hemorrhagic Fever
Dengue Shock Syndrome

Additional relevant MeSH terms:
Dengue
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral

ClinicalTrials.gov processed this record on April 17, 2014