Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3/4delta30[ME]) 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:
NCT00375726
First received: September 12, 2006
Last updated: December 13, 2010
Last verified: December 2010
  Purpose

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.


Condition Intervention Phase
Dengue
Biological: rDEN3/4delta30(ME)
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 rDEN3/4delta30(ME), a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 3

Resource links provided by NLM:


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

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]
  • Immunogenicity, as determined by anti-DEN3 neutralizing antibody measured on Days 0, 21, 28, 42, and 180 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the frequency, quantity, and duration of viremia in each dose cohort studied [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Determine the number of vaccinees infected with rDEN3/4delta30(ME) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Compare the infectivity rates, safety, and immunogenicity between dose groups [ Time Frame: At study completion ] [ Designated as safety issue: No ]
  • Evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 58
Study Start Date: October 2006
Study Completion Date: September 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00375726

Locations
United States, Maryland
Center for Immunization Research
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Johns Hopkins Bloomberg School of Public Health
Investigators
Principal Investigator: Anna Durbin, MD Center for Immunization Research, 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: NCT00375726     History of Changes
Other Study ID Numbers: CIR 228, WIRB Protocol Number 20061667
Study First Received: September 12, 2006
Last Updated: December 13, 2010
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 September 16, 2014