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

Phase I Study of the Safety and Immunogenicity of rDEN1delta30, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 1

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.

Study Overview

• Status: Completed
• Conditions: Dengue Fever
• Intervention / Treatment: Biological: rDEN1delta30; Biological: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Center for Immunization Research, Johns Hopkins School of Public Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; One subcutaneous vaccination with rDEN1delta30 vaccine (10^3 PFU dose) into the deltoid region of either arm.	Biological: rDEN1delta30; Live attenuated rDEN1delta30 vaccine
Experimental: 2; One subcutaneous vaccination with rDEN1delta30 vaccine (10^5 PFU dose) into the deltoid region of either arm. This arm may enroll after Arm 1 depending on the effect of the vaccine on subjects in Arm 1.	Biological: rDEN1delta30; Live attenuated rDEN1delta30 vaccine
Placebo Comparator: 3; One subcutaneous vaccination with placebo into the deltoid region of either arm.	Biological: Placebo; Placebo for rDEN1delta30

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Determine the frequency of vaccine related AEs for each dose graded by severity	Throughout study
Determine the amount of dengue 1 neutralizing antibody induced by the vaccine	At Day 42

Secondary Outcome Measures

Outcome Measure	Time Frame
To assess the durability of the antibody response	At Day 180
To assess the frequency, quantity, and duration of viremia in each dose cohort studied	Throughout study
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
If both doses of vaccine are administered, to compare the infectivity rates, safety, and immunogenicity between dose groups	At study completion
To evaluate the immunopathological mechanism of vaccine-associated rash in those volunteers who are willing to undergo skin biopsy	Throughout study

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Johns Hopkins Bloomberg School of Public Health
• Investigators: Principal Investigator: Anna Durbin, MD, Center for Immunization Research, John Hopkins School of Public Health

Publications and helpful links

General Publications

• Jacobs M, Young P. Dengue vaccines: preparing to roll back dengue. Curr Opin Investig Drugs. 2003 Feb;4(2):168-71.
• Pang T. Vaccines for the prevention of neglected diseases--dengue fever. Curr Opin Biotechnol. 2003 Jun;14(3):332-6. doi: 10.1016/s0958-1669(03)00061-2.
• Rothman AL. Dengue: defining protective versus pathologic immunity. J Clin Invest. 2004 Apr;113(7):946-51. doi: 10.1172/JCI21512.
• 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. doi: 10.4269/ajtmh.2003.69.6_suppl.0690024.

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): November 1, 2005
• Study Completion (Actual): November 1, 2005

Study Registration Dates

• First Submitted: August 17, 2004
• First Submitted That Met QC Criteria: August 18, 2004
• First Posted (Estimate): August 19, 2004

Study Record Updates

• Last Update Posted (Estimate): January 18, 2008
• Last Update Submitted That Met QC Criteria: January 17, 2008
• Last Verified: January 1, 2008

More Information

Terms related to this study

• Keywords: Dengue Hemorrhagic Fever; Dengue Vaccine; Dengue Virus; Dengue Shock Syndrome
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Hemorrhagic Fevers, Viral; Dengue
• Other Study ID Numbers: CIR 199; H.22.04.04.23.B2