Safety of and Immune Response to a Dengue Virus Vaccine (rDEN1delta30) in Healthy Adults

Dengue Fever Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00089908
• Other study ID #: CIR 199
• Secondary ID: H.22.04.04.23.B2
• Status: Completed
• Phase: Phase 1
• First received: August 17, 2004
• Last updated: January 17, 2008
• Start date: September 2004
• Est. completion date: November 2005

Study information

• Verified date: January 2008
• 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:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: November 2005
• Est. primary completion date: November 2005
• 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, 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

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:
• rDEN1delta30
Live attenuated rDEN1delta30 vaccine
• Placebo
Placebo for rDEN1delta30

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 (4)

Jacobs M, Young P. Dengue vaccines: preparing to roll back dengue. Curr Opin Investig Drugs. 2003 Feb;4(2):168-71. Review. — View Citation

Pang T. Vaccines for the prevention of neglected diseases--dengue fever. Curr Opin Biotechnol. 2003 Jun;14(3):332-6. 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	Determine the frequency of vaccine related AEs for each dose graded by severity		Throughout study	Yes
Primary	Determine the amount of dengue 1 neutralizing antibody induced by the vaccine		At Day 42	No
Secondary	To assess the durability of the antibody response		At Day 180	No
Secondary	To assess the frequency, quantity, and duration of viremia in each dose cohort studied		Throughout study	No
Secondary	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		Throughout study	No
Secondary	If both doses of vaccine are administered, to compare the infectivity rates, safety, and immunogenicity between dose groups		At study completion	No
Secondary	To evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy		Throughout study	No