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

Dengue Fever Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00270699
• Other study ID #: CIR 214
• Secondary ID: WIRB Protocol Nu
• Status: Completed
• Phase: Phase 1
• First received: December 27, 2005
• Last updated: December 31, 2012
• Start date: June 2006
• Est. completion date: December 2009

Study information

• Verified date: December 2012
• 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Dengue
• Dengue Fever

Intervention

Biological:
• rDEN4delta30-200,201
Live attenuated dengue 4 vaccine (one of three doses)
• Placebo
Placebo for rDEN4delta30-200,201

Locations

Country	Name	City	State
United States	Center for Immunization Research, Johns Hopkins School of Public Health	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 (5)

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

Malavige GN, Fernando S, Fernando DJ, Seneviratne SL. Dengue viral infections. Postgrad Med J. 2004 Oct;80(948):588-601. Review. — View Citation

Rothman AL. Dengue: defining protective versus pathologic immunity. J Clin Invest. 2004 Apr;113(7):946-51. Review. — View Citation

Sun W, Edelman R, Kanesa-Thasan N, Eckels KH, Putnak JR, King AD, Houng HS, Tang D, Scherer JM, Hoke CH Jr, Innis BL. Vaccination of human volunteers with monovalent and tetravalent live-attenuated dengue vaccine candidates. Am J Trop Med Hyg. 2003 Dec;69(6 Suppl):24-31. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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		Throughout study	Yes
Primary	Determine the number of vaccinees who have seroconverted to DEN4 up to and including Day 42		At 42 days	No
Secondary	Durability of antibody responses to DEN4 virus		At 180 days	No
Secondary	Frequency, quantity, and duration of viremia in each dose cohort		Thoughout study	No
Secondary	Number of vaccinees infected with vaccine virus in each dose cohort		Throughout study	No
Secondary	Duration of antibody response determined by serum neutralizing antibody		At 180 days	No
Secondary	Determine cellular targets of vaccine infection in participants willing to undergo skin biopsy		Throughout study	No
Secondary	Compare infectivity rates, safety, and immunogenicity between dose cohorts		At study completion	Yes
Secondary	Evaluate immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy		Throughout study	No