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Safety of and Immune Response to Two Different Dengue Virus Vaccines in Individuals Previously Immunized Against Dengue Virus

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:
NCT00458120
First received: April 6, 2007
Last updated: December 13, 2010
Last verified: December 2010
  Purpose

Dengue fever, which is caused by dengue viruses, is a major health problem in subtropical regions of the world. There are four different forms (serotypes) of dengue virus that can cause dengue fever. The purpose of this study is to determine the safety and immune response to a vaccine containing a particular dengue serotype when an individual has been previously vaccinated with a different dengue serotype.


Condition Intervention Phase
Dengue Hemorrhagic Fever
Biological: rDEN1delta30
Biological: rDEN2/4delta30(ME)
Biological: Placebo to rDEN1delta30 or rDEN2/4delta30(ME)
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: Evaluation of the Safety and Immunogenicity of Heterologous Dengue Vaccine Administration in Dengue Immune Individuals

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Neutralizing antibody to all four dengue serotypes [ Time Frame: At Days 0, 28, and 42 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Assess the frequency, quantity, and duration of viremia in each vaccine cohort studied [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • To determine if cellular targets of vaccine infection, including peripheral blood mononuclear cells and skin, are different after heterologous infection of a second dengue virus vaccine of a different serotype [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Compare the safety and immunogenicity between each heterologous dengue vaccine virus cohort [ Time Frame: At study completion ] [ Designated as safety issue: No ]
  • Evaluate the immunopathological mechanism of heterologous vaccine virus associated rash in those volunteers who are willing to undergo skin biopsy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  • Characterize the antibody response after heterolouous vaccine infection [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: March 2007
Study Completion Date: August 2008
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Participants previously vaccinated with rDEN4delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN1delta30 vaccine into the deltoid region of either arm.
Biological: rDEN1delta30
Live attenuated 10^3 dose of rDEN1delta30 vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN2/4delta30(ME) vaccines.
Experimental: 2
Participants previously vaccinated with rDEN4delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN2/4delta30(ME) into the deltoid region of either arm.
Biological: rDEN2/4delta30(ME)
Live attenuated 10^3 dose of rDEN2/4delta30(ME) vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN1delta30 vaccines.
Experimental: 3
Participants previously vaccinated with rDEN2/4delta30(ME) will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN1delta30 vaccine into the deltoid region of either arm.
Biological: rDEN1delta30
Live attenuated 10^3 dose of rDEN1delta30 vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN2/4delta30(ME) vaccines.
Experimental: 4
Participants previously vaccinated with rDEN1delta30 will receive one subcutaneous vaccination (10^3 dose of vaccine) of rDEN2/4delta30(ME) vaccine into the deltoid region of either arm.
Biological: rDEN2/4delta30(ME)
Live attenuated 10^3 dose of rDEN2/4delta30(ME) vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN1delta30 vaccines.
Placebo Comparator: 5
One subcutaneous vaccination with placebo into the deltoid region of either arm.
Biological: Placebo to rDEN1delta30 or rDEN2/4delta30(ME)
Placebo vaccines for rDEN1delta30 and rDEN2/4delta30(ME)

Detailed Description:

The World Health Organization estimates that dengue virus causes more than 50 million cases of dengue fever a year. Dengue virus infection is the leading cause of hospitalization and death in children of most tropical Asian countries. There are four different serotypes of dengue virus. Most cases of dengue hemorrhagic fever/dengue shock syndrome are caused by secondary infection with a dengue serotype different from the first serotype the individual was infected with. A vaccine that would be effective in preventing infection by multiple dengue serotypes is desirable. The purpose of this study is to determine the safety of and immune response to two different dengue virus vaccines in individuals who have been previously vaccinated against a different serotype.

This study will last at least 42 days. Participants will be recruited from a database of previous dengue vaccine recipients and will be stratified by the type of vaccine previously received. Participants assigned to Cohort 1 and Cohort 2 will have already been vaccinated with the rDEN4delta30 vaccine. Participants assigned to Cohort 3 will have already been vaccinated with the rDEN2/4delta30(ME) vaccine. Participants in Cohort 4 will have already been vaccinated with the rDEN1delta30 vaccine. Participants in Cohorts 1 and 3 will be randomly assigned to receive either the rDEN1delta30 vaccine or placebo. Participants in Cohorts 2 and 4 will be randomly assigned to receive either the rDEN2/4delta30(ME) vaccine or placebo.

Participants will receive their assigned vaccination on Day 0. Study visits will occur every other day until Day 16, and then at Days 21, 28, and 42. At each visit, blood collection, vital signs measurement, and a physical exam will occur. In addition, participants will be asked to monitor their temperature daily, 3 times a day, from Day 0 to Day 16. Patients will also be asked to enroll in an optional skin biopsy sub-study.

  Eligibility

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

Inclusion Criteria:

  • Previous vaccination with rDEN1delta30, rDEN2/4delta30(ME), OR rDEN4delta30 vaccine
  • General good health
  • Available for the duration of the study
  • Willing to use accepted forms of contraception

Exclusion Criteria:

  • Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease by history, physical examination, or laboratory studies including urinalysis
  • Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study
  • Certain abnormal laboratory values
  • Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months of study entry
  • History of severe allergy or anaphylaxis
  • Severe asthma requiring an emergency room visit or hospitalization within 6 months of study entry
  • HIV infected
  • Hepatitis C virus infected
  • Hepatitis B surface antibody positive
  • Known immunodeficiency syndrome
  • Use of corticosteroids or immunosuppressive drugs 30 days prior to study entry. Participants who have used topical or nasal corticosteroids are not excluded.
  • Receipt of live vaccine within 4 weeks of study entry
  • Receipt of killed vaccine within 2 weeks of study entry
  • Absence of spleen
  • Plan to travel to an area where dengue virus is common
  • Any investigational product within 30 days of 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: NCT00458120

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:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Anna Durbin, MD, Center for Immunization Research, Johns Hopkins School of Public Health
ClinicalTrials.gov Identifier: NCT00458120     History of Changes
Other Study ID Numbers: CIR 227, WIRB Protocol Number 20070409
Study First Received: April 6, 2007
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 Hemorrhagic Fever
Dengue Vaccination

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

ClinicalTrials.gov processed this record on November 19, 2014