Clinical trial NCT00458120: Safety of and Immune Response to Two Different Dengue Virus Vaccines in Individuals Previously Immunized Against Dengue Virus
Official title: Evaluation of the Safety and Immunogenicity of Heterologous Dengue Vaccine Administration in Dengue Immune Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dengue Hemorrhagic Fever
Keywords: Dengue Fever
Dengue Hemorrhagic Fever
Dengue Vaccination
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Johns Hopkins Bloomberg School of Public Health
First posted: 2007-04-09
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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 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

Primary outcomes:
measure: Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance
timeFrame: Throughout study
measure: Neutralizing antibody to all four dengue serotypes
timeFrame: At Days 0, 28, and 42
Secondary outcomes:
measure: Assess the frequency, quantity, and duration of viremia in each vaccine cohort studied
timeFrame: Throughout study
measure: 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
timeFrame: Throughout study
measure: Compare the safety and immunogenicity between each heterologous dengue vaccine virus cohort
timeFrame: At study completion
measure: Evaluate the immunopathological mechanism of heterologous vaccine virus associated rash in those volunteers who are willing to undergo skin biopsy
timeFrame: Throughout study
measure: Characterize the antibody response after heterolouous vaccine infection
timeFrame: Throughout study
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Center for Immunization Research
state: Maryland
Study officials:
affiliation: Center for Immunization Research, Johns Hopkins School of Public Health
name: Anna Durbin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Durbin AP, Whitehead SS, McArthur J, Perreault JR, Blaney JE Jr, Thumar B, Murphy BR, Karron RA. rDEN4delta30, a live attenuated dengue virus type 4 vaccine candidate, is safe, immunogenic, and highly infectious in healthy adult volunteers. J Infect Dis. 2005 Mar 1;191(5):710-8. doi: 10.1086/427780. Epub 2005 Jan 27.
citation: Chaturvedi UC, Shrivastava R, Nagar R. Dengue vaccines: problems and prospects. Indian J Med Res. 2005 May;121(5):639-52.
citation: Guzman MG, Mune M, Kouri G. Dengue vaccine: priorities and progress. Expert Rev Anti Infect Ther. 2004 Dec;2(6):895-911. doi: 10.1586/14789072.2.6.895.
citation: Durbin AP, Schmidt A, Elwood D, Wanionek KA, Lovchik J, Thumar B, Murphy BR, Whitehead SS. Heterotypic dengue infection with live attenuated monotypic dengue virus vaccines: implications for vaccination of populations in areas where dengue is endemic. J Infect Dis. 2011 Feb 1;203(3):327-34. doi: 10.1093/infdis/jiq059. Epub 2010 Dec 14.