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

Dengue Hemorrhagic Fever Clinical Trial

Official title:

Evaluation of the Safety and Immunogenicity of Heterologous Dengue Vaccine Administration in Dengue Immune Individuals

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00458120
• Other study ID #: CIR 227
• Secondary ID: WIRB Protocol Nu
• Status: Completed
• Phase: Phase 1
• First received: April 6, 2007
• Last updated: December 13, 2010
• Start date: March 2007
• Est. completion date: August 2008

Study information

• Verified date: December 2010
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Dengue
• Dengue Hemorrhagic Fever
• Severe Dengue

Intervention

Biological:
• rDEN1delta30
Live attenuated 10^3 dose of rDEN1delta30 vaccine. Participants must have been previously vaccinated with rDEN4delta30 or rDEN2/4delta30(ME) vaccines.
• 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 to rDEN1delta30 or rDEN2/4delta30(ME)
Placebo vaccines for rDEN1delta30 and rDEN2/4delta30(ME)

Locations

Country	Name	City	State
United States	Center for Immunization Research	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Johns Hopkins Bloomberg School of Public Health

Country where clinical trial is conducted

United States, 

References & Publications (3)

Chaturvedi UC, Shrivastava R, Nagar R. Dengue vaccines: problems and prospects. Indian J Med Res. 2005 May;121(5):639-52. Review. — View 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. Epub 2005 Jan 27. — View Citation

Guzmán MG, Muné M, Kourí G. Dengue vaccine: priorities and progress. Expert Rev Anti Infect Ther. 2004 Dec;2(6):895-911. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number, severity, and seriousness of vaccine-related adverse events observed through active and passive surveillance		Throughout study	Yes
Primary	Neutralizing antibody to all four dengue serotypes		At Days 0, 28, and 42	No
Secondary	Assess the frequency, quantity, and duration of viremia in each vaccine cohort studied		Throughout study	No
Secondary	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		Throughout study	No
Secondary	Compare the safety and immunogenicity between each heterologous dengue vaccine virus cohort		At study completion	No
Secondary	Evaluate the immunopathological mechanism of heterologous vaccine virus associated rash in those volunteers who are willing to undergo skin biopsy		Throughout study	No
Secondary	Characterize the antibody response after heterolouous vaccine infection		Throughout study	No