Safety of and Immune Response to a Dengue Virus Vaccine (rDEN1delta30) 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:
NCT00089908
First received: August 17, 2004
Last updated: January 17, 2008
Last verified: January 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 test the safety of and immune response to a new dengue virus vaccine in healthy adults.


Condition Intervention Phase
Dengue Fever
Biological: rDEN1delta30
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 I Study of the Safety and Immunogenicity of rDEN1delta30, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 1

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Determine the frequency of vaccine related AEs for each dose graded by severity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Determine the amount of dengue 1 neutralizing antibody induced by the vaccine [ Time Frame: At Day 42 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the durability of the antibody response [ Time Frame: At Day 180 ] [ Designated as safety issue: No ]
  • To assess the frequency, quantity, and duration of viremia in each dose cohort studied [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • To compare the T cell mediated immune response against dengue viruses of those volunteers infected with the rDEN1delta30 vaccine virus with that of uninfected volunteers and placebo recipients [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • If both doses of vaccine are administered, to compare the infectivity rates, safety, and immunogenicity between dose groups [ Time Frame: At study completion ] [ Designated as safety issue: No ]
  • To 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: 28
Study Start Date: September 2004
Study Completion Date: November 2005
Primary Completion Date: November 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
One subcutaneous vaccination with rDEN1delta30 vaccine (10^3 PFU dose) into the deltoid region of either arm.
Biological: rDEN1delta30
Live attenuated rDEN1delta30 vaccine
Experimental: 2
One subcutaneous vaccination with rDEN1delta30 vaccine (10^5 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the effect of the vaccine on subjects in Arm 1.
Biological: rDEN1delta30
Live attenuated rDEN1delta30 vaccine
Placebo Comparator: 3
One subcutaneous vaccination with placebo into the deltoid region of either arm.
Biological: Placebo
Placebo for rDEN1delta30

Detailed Description:

More than 2 billion people living in tropical and subtropical regions of the world are at risk of dengue virus infection. Dengue viruses cause dengue fever, as well as the more severe dengue hemorrhagic fever/shock syndrome, and dengue virus infection 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 called rDEN1delta30, which is derived from the Western Pacific DEN1 serotype.

This study will last 180 days. Participants in Cohort 1 will be randomly assigned to receive rDEN1delta30 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 higher dose of rDEN1delta30 or placebo.

After vaccination, participants will be asked to monitor their temperature every day for 16 days. Study visits will occur every other day after vaccination until Day 16, followed by 4 additional visits at selected days through Day 180. Blood collection 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, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease
  • Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the ability of the volunteer to understand and cooperate with the study
  • Liver, renal, or hematologic disease
  • Alcohol or drug abuse within 12 months of study entry
  • History of severe allergic reaction or anaphylaxis
  • Emergency room visit or hospitalization for severe asthma within 6 months of study entry
  • HIV-1 infected
  • HCV infected
  • Hepatitis B surface antigen positive
  • Known immunodeficiency syndrome
  • Use of corticosteroids or immunosuppressive drugs within 30 days of study entry. Participants who have used topical or nasal corticosteroids are not excluded.
  • Live vaccine within 4 weeks of study entry
  • Killed vaccine within 2 weeks of study entry
  • Blood products within 6 months of study entry
  • Investigational drugs or vaccines within 60 days prior to study entry or while currently enrolled in this clinical trial
  • Previously received a licensed or experimental yellow fever or dengue vaccine
  • Surgical removal of spleen
  • History of dengue virus infection or other flavivirus infection
  • Other condition that, in the opinion of the investigator, would affect the participant's participation in the study
  • Pregnancy or breastfeeding
  • Plan to travel to an area where dengue infection is common
  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: NCT00089908

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, John 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: NCT00089908     History of Changes
Other Study ID Numbers: CIR 199, H.22.04.04.23.B2
Study First Received: August 17, 2004
Last Updated: January 17, 2008
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