Safety of and Immune Response of a 2-Dose Regimen of rDEN1delta30 Dengue Virus Vaccine - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Center for Immunization Research
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00473135

Purpose

Dengue fever, caused by dengue viruses, is a major health problem in tropical and subtropical regions of the world. The purpose of this study is to evaluate the safety of and immune response to a 2-dose regimen of a new monovalent dengue virus vaccine. This study will test the dengue virus vaccine DEN1delta30 in healthy adults.

Condition	Intervention	Phase
Dengue	Biological: rDEN1delta30 Biological: Placebo	Phase I

Study Type:	Interventional
Study Design:	Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety Study
Official Title:	Safety and Immunogenicity of a 2-Dose Regimen of rDEN1delta30 Dengue Serotype 1 Vaccine With Boosting at 4 Versus 6 Months

Resource links provided by NLM:

MedlinePlus related topics: Dengue Fever

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

To determine the safety and immunogenicity of a two-dose regimen of the rDEN1delta30 vaccine given as two doses separated by four or six months [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
To determine the optimum interval between first and second dose of rDEN1delta30 vaccine, as assessed by neutralizing antibody response to DEN1 induced by the vaccine [ Time Frame: At 4 and 6 weeks after first and second vaccination ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To assess the frequency, quantity, and duration of viremia following each vaccine dose, based on the mean peak viremia, mean day of onset, and mean duration of viremia [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
To determine the number of vaccinees infected with rDEN1delta30 virus [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
To compare the infectivity rates, safety, and immunogenicity between dose 1 and 2 within a cohort and between cohorts [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
To evaluate the immunopathological mechanism of vaccine-associated rash in participants willing to undergo skin biopsy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
To evaluate the phenotype and activation of peripheral blood mononuclear cells (PBMCs) at primary infection and challenge with DEN1 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	May 2007
Estimated Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Two subcutaneous vaccinations with rDEN1delta30 into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on Day 120.	Biological: rDEN1delta30 Live attenuated rDEN1delta30 vaccine at a dose of 10^3 PFU
2: Experimental Two subcutaneous vaccinations with rDEN1delta30 into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on Day 180.	Biological: rDEN1delta30 Live attenuated rDEN1delta30 vaccine at a dose of 10^3 PFU
3: Placebo Comparator Two subcutaneous vaccinations with placebo into the deltoid region or either arm. One vaccination is given on Day 0 and one vaccination is given on either Day 120 or 180, depending on arm assignment.	Biological: Placebo Placebo for rDEN1delta30

Detailed Description:

Dengue viruses account for more than 50 million cases of dengue fever and one half million cases annually of dengue hemorrhagic fever/shock syndrome. Dengue virus infections can cause illness ranging from mild, self-limited febrile illness to life threatening diseases. The goal of dengue vaccine development is to induce a long-lived antibody response against all four dengue serotypes. The rDEN1delta30 vaccine is a live attenuated dengue virus vaccine that may be protective against dengue serotype 1 (DEN1). The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of a 2-dose regimen of rDEN1delta30 dengue virus vaccine. The regimen will differ in when the second booster shot of the vaccine is given.

This study will last 162 days (about 23 weeks) for those participants in Cohort 1, and 222 days (about 32 weeks) for those in Cohort 2. Participants in Cohort 1 will be randomly assigned to receive rDEN1delta30 vaccine or placebo on Study Day 0 and Study Day 120. Participants in Cohort 2 will be randomly assigned to receive rDEN1delta30 vaccine or placebo on Study Day 0 and Study Day 180.

There will be a total of 25 visits for each cohort. For both cohorts, the first and second vaccination days will include a physical exam and blood and urine collection, vital signs measurements, and receipt of the vaccine. A 30 minute observation period will follow vaccination. Participants will take their temperature at home three times a day for the first 16 days and report it in a diary. At all other study visits, vital signs measurements, a physical exam, and blood and/or urine collection will occur. At selected study visits, participants will turn in their diary cards.

Some participants may be asked to join an optional skin biopsy substudy.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Good general health
Available for the duration of the study (23 weeks for Cohort 1 and 32 weeks for Cohort 2)
Willing to use acceptable forms of contraception for the duration of the study

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 interfere with the study
Significant laboratory abnormalities
Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months prior to study entry
History of severe allergic reaction or anaphylaxis
Severe asthma
HIV-1 infected
Hepatitis C virus (HCV) infected
Hepatitis B surface antigen positive
Known immunodeficiency syndrome
Use of corticosteroids or immunosuppressive medications within 30 days prior to study entry. Individuals using topical or nasal corticosteroids are not excluded.
Previous receipt of a live vaccine within 4 weeks prior to study entry
Previous receipt of a killed vaccine within 2 weeks prior to study entry
Absence of spleen
Previous receipt of blood products within 6 months prior to study entry
Previous receipt of dengue virus or other flavivirus (e.g., yellow fever virus, St.Louis encephalitis, West Nile virus) infection
Previous receipt of yellow fever or dengue vaccine
Plans to travel to an area where dengue infection is common
Previous receipt of any investigational agent within 30 days prior to study entry
Other condition that, in the opinion of the investigator, would affect participation in the study
Pregnant or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00473135

Contacts

Contact: Central Recruiting Line

410-955-7283

Locations

United States, Maryland
Center for Immunization Research, Johns Hopkins School of Public Health	Recruiting
Baltimore, Maryland, United States, 21205
Contact: Daniel Elwood, RN, CCRC 410-614-1880 delwood@jhsph.edu
Contact: Priscilla Brooks, RN, CCRC 410-614-4625 pbrooks@jhsph.edu

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Center for Immunization Research

Investigators

Principal Investigator:

Anna Durbin, MD

Center for Immunization Research (CIR), Johns Hopkins School of Public Health

More Information

Publications:

Blaney JE Jr, Sathe NS, Hanson CT, Firestone CY, Murphy BR, Whitehead SS. Vaccine candidates for dengue virus type 1 (DEN1) generated by replacement of the structural genes of rDEN4 and rDEN4Delta30 with those of DEN1. Virol J. 2007 Feb 28;4:23.

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

Durbin AP, McArthur J, Marron JA, Blaney JE Jr, Thumar B, Wanionek K, Murphy BR, Whitehead SS. The live attenuated dengue serotype 1 vaccine rDEN1Delta30 is safe and highly immunogenic in healthy adult volunteers. Hum Vaccin. 2006 Jul-Aug;2(4):167-73. Epub 2006 Jul 24.

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

Pang T. Vaccines for the prevention of neglected diseases--dengue fever. Curr Opin Biotechnol. 2003 Jun;14(3):332-6. Review.

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

Senanayake S. Dengue fever and dengue haemorrhagic fever--a diagnostic challenge. Aust Fam Physician. 2006 Aug;35(8):609-12. Review.

Responsible Party:	Center for Immunization Research, Johns Hopkins School of Public Health ( Anna Durbin, MD )
Study ID Numbers:	CIR 229, WIRB Protocol Number 20070718
Study First Received:	May 11, 2007
Last Updated:	January 15, 2008
ClinicalTrials.gov Identifier:	NCT00473135 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Dengue Fever
Dengue Vaccine
Dengue Virus
Dengue Hemorrhagic Fever
Dengue Shock Syndrome

Additional relevant MeSH terms:

Virus Diseases
Hemorrhagic Fevers, Viral
RNA Virus Infections
Flaviviridae Infections

Flavivirus Infections
Dengue
Arbovirus Infections

ClinicalTrials.gov processed this record on November 27, 2009