Safety of and Immune Response to a Dengue Virus Vaccine (rDEN2/4delta30[ME]) in Healthy Adults

Dengue Fever Clinical Trial

Official title:

Phase 1 Study of the Safety and Immunogenicity of rDEN2/4delta30(ME), a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 2

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00094705
• Other study ID #: CIR 189
• Secondary ID: H.22.03.09.26.A2
• Status: Completed
• Phase: Phase 1
• First received: October 21, 2004
• Last updated: January 18, 2008
• Start date: January 2005
• Est. completion date: April 2006

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:

Dengue viruses cause dengue fever, as well as 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 rDEN2/4delta30(ME), which is derived from the DEN2 and DEN4 serotypes.

This study will last 180 days. Participants in Cohort 1 will be randomly assigned to receive rDEN2/4delta30(ME) 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 rDEN2/4delta30(ME) or placebo.

After vaccination, participants will be observed for at least 30 minutes for immediate adverse reactions. Participants will also 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: April 2006
• Est. primary completion date: April 2006
• 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

• Hematologic disease

• 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

• Participation in another investigational vaccine or drug trial within 60 days of starting this study, or while this trial is ongoing

• 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, 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 Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Dengue
• Dengue Fever

Intervention

Biological:
• rDEN2/4delta30(ME) Vaccine
Live attenuated rDEN2/4delta30(ME) vaccine (one of two doses)
• Placebo
Placebo for rDEN2/4delta30(ME) vaccine

Locations

Country	Name	City	State
United States	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)

Edelman R. Dengue and dengue vaccines. J Infect Dis. 2005 Mar 1;191(5):650-3. 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

Sabchareon A, Lang J, Chanthavanich P, Yoksan S, Forrat R, Attanath P, Sirivichayakul C, Pengsaa K, Pojjaroen-Anant C, Chokejindachai W, Jagsudee A, Saluzzo JF, Bhamarapravati N. Safety and immunogenicity of tetravalent live-attenuated dengue vaccines in Thai adult volunteers: role of serotype concentration, ratio, and multiple doses. Am J Trop Med Hyg. 2002 Mar;66(3):264-72. — 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

Whitehead SS, Hanley KA, Blaney JE Jr, Gilmore LE, Elkins WR, Murphy BR. Substitution of the structural genes of dengue virus type 4 with those of type 2 results in chimeric vaccine candidates which are attenuated for mosquitoes, mice, and rhesus monkeys. Vaccine. 2003 Oct 1;21(27-30):4307-16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency and severity of vaccine-related adverse effects for each dose graded by severity		Throughout study	No
Primary	Amount of dengue 2 neutralizing antibody induced by the vaccine		At Day 42	No
Secondary	To assess the durability of the antibody response out to Day 180		Throughout study	No
Secondary	To assess the frequency, quantity, and duration of viremia in each dose cohort studied		Throughout study	No
Secondary	To determine the number of vaccinees infected with rDEN2/4delta30(ME)		Throughout study	No
Secondary	To compare the T cell mediated immune response against dengue viruses of those volunteers infected with the rDEN2/4delta30(ME) 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