Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-200,201) in Healthy Adults

This study has been completed.
Sponsor:
Collaborator:
Johns Hopkins Bloomberg School of Public Health
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00270699
First received: December 27, 2005
Last updated: December 31, 2012
Last verified: December 2012
  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 test the safety of and immune response to a new dengue virus vaccine in healthy adults.


Condition Intervention Phase
Dengue Fever
Biological: rDEN4delta30-200,201
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 rDEN4delta30-200,201, 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, as classified by intensity and severity through active and passive surveillance and separate assessments of systemic and local reactions [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Determine the number of vaccinees who have seroconverted to DEN4 up to and including Day 42 [ Time Frame: At 42 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Durability of antibody responses to DEN4 virus [ Time Frame: At 180 days ] [ Designated as safety issue: No ]
  • Frequency, quantity, and duration of viremia in each dose cohort [ Time Frame: Thoughout study ] [ Designated as safety issue: No ]
  • Number of vaccinees infected with vaccine virus in each dose cohort [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Duration of antibody response determined by serum neutralizing antibody [ Time Frame: At 180 days ] [ Designated as safety issue: No ]
  • Determine cellular targets of vaccine infection in participants willing to undergo skin biopsy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Compare infectivity rates, safety, and immunogenicity between dose cohorts [ Time Frame: At study completion ] [ Designated as safety issue: Yes ]
  • Evaluate immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 56
Study Start Date: June 2006
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^5 PFU dose) into the deltoid region of either arm.
Biological: rDEN4delta30-200,201
Live attenuated dengue 4 vaccine (one of three doses)
Experimental: 2
One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^3 PFU dose) into the deltoid region of either arm. This arm will enroll after Arm 1.
Biological: rDEN4delta30-200,201
Live attenuated dengue 4 vaccine (one of three doses)
Experimental: 3
One subcutaneous vaccination with rDEN4delta30-200,201 vaccine (10^1 PFU dose) into the deltoid region of either arm. This arm will enroll after Arms 1 and 2.
Biological: rDEN4delta30-200,201
Live attenuated dengue 4 vaccine (one of three doses)
Placebo Comparator: 4
One subcutaneous vaccination with placebo into the deltoid region of either arm.
Biological: Placebo
Placebo for rDEN4delta30-200,201

Detailed Description:

Dengue viruses cause dengue fever and the more severe dengue hemorrhagic fever/shock syndrome. More than 2 billion people living in tropical and subtropical regions of the world are at risk of dengue virus infection, which is the leading cause of hospitalization and death in children in several tropical Asian countries. This study will evaluate the safety and immunogenicity of a live attenuated dengue virus vaccine called rDEN4delta30-200,201. This vaccine is derived from rDEN4delta30, another dengue virus vaccine candidate that has been shown to be safe and immunogenic in Phase I and II trials in healthy adults.

This study will last 180 days. There will be three cohorts in this dose de-escalation study. Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30-200,201 or placebo at study entry. Cohort 2 will begin only after safety review of all participants in Cohort 1. Participants in Cohort 2 will receive a lower dose of rDEN4delta30-200,201 or placebo. Cohort 3 will begin only after safety review of all participants in Cohort 2. Participants in Cohort 3 will receive the lowest dose of rDEN4delta30-200,201 or placebo.

After vaccination, participants will be asked to monitor their temperatures every day for 16 days. Study visits will occur every other day after vaccination until Day 16, followed by four additional visits at selected days through Day 180. Blood collection, vital signs measurement, and a targeted physical exam will occur at each study visit. Some participants will 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:

  • Willing to be followed for the duration of the study
  • Willing to use acceptable methods of contraception
  • Good general health

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 affect the ability of the volunteer to understand and cooperate with the study
  • Laboratory abnormalities at study screening
  • Alcohol or drug abuse 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 infected
  • Hepatitis B surface antigen positive
  • Known immunodeficiency syndrome
  • Use of corticosteroids or immunosuppressive drugs within 30 days prior to study entry. Participants who have used 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
  • Blood products within 6 months prior to study entry
  • Previously received a licensed or experimental yellow fever or dengue vaccine
  • Surgical removal of spleen
  • History of dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis virus, West Nile virus, Japanese encephalitis virus)
  • Other condition that, in the opinion of the investigator, would affect the participant's participation in the study
  • Plan to travel to an area where dengue infection is common
  • 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: NCT00270699

Locations
United States, Maryland
Center for Immunization Research, Johns Hopkins School of Public Health
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: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00270699     History of Changes
Other Study ID Numbers: CIR 214, WIRB Protocol Number 2006478
Study First Received: December 27, 2005
Last Updated: December 31, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
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 October 19, 2014