Safety of and Immune Response to a Dengue Virus Vaccine (rDEN4delta30-4995) in Healthy Adults

Dengue Clinical Trial

Official title:

Phase 1 Study of the Safety and Immunogenicity of rDEN4delta30-4995, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 4

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00322946
• Other study ID #: CIR 221
• Secondary ID: WIRB Protocol Nu
• Status: Completed
• Phase: Phase 1
• First received: May 4, 2006
• Last updated: August 5, 2009
• Start date: January 2007

Study information

• Verified date: November 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 evaluate the safety and immune response to the dengue vaccine DEN4delta30-4995 in healthy adults.

Description:

Dengue viruses account for more than 50 million cases of dengue fever and a half million cases of the more severe disease, dengue hemorrhagic fever/dengue shock syndrome. Infection with dengue viruses is the leading cause of hospitalization and death in children in at least eight Asian countries. The goal of producing a vaccine against dengue fever is to induce a long-lived antibody response against all four dengue serotypes. The rDEN4delta30-4995 vaccine candidate is a live attenuated recombinant virus derived from rDEN4delta30 for protection against dengue virus serotype 4. The purpose of this study is to evaluate the safety, reactogenicity, and immunogenicity of rDEN4delta30-4995 in healthy adults.

This study will last 180 days (6 months). Participants in Cohort 1 will be randomly assigned to receive the highest dose of rDEN4delta30 or placebo at study entry. Participants in Cohort 2 will be randomly assigned to receive a lower dose of rDEN4delta30 or placebo. Participants in Cohort 3 will be randomly assigned to receive the lowest dose of rDEN4delta30 or placebo. Cohorts 2 and 3 will begin after a safety review of all participants in the previous cohort.

After initial vaccination, participants in Cohort 1 will be followed every other day for the first 16 days of the study, monitoring their temperature three times a day through Day 16 and recording these measurements in a diary. After Day 16, study visits will occur on Days 21, 28, 42, and 180 and will include a physical exam and blood collection. Some participants will also be asked to undergo a skin biopsy or additional blood collection at selected visits.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. primary completion date: August 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• Adult males and non-pregnant females between 18 and 50 years of age

• Good general health

• Available for the duration of the study

• Willing to use acceptable methods of contraception for the duration of the study

Exclusion Criteria:

• Significant neurologic, cardiac, 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 serotype infected

• Hepatitis C virus (HCV) infected

• Hepatitis B surface antigen positive

• Immunodeficiency syndrome

• Use of corticosteroids or immunosuppressive medications within 2 weeks prior to study entry. Individuals using 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

• Absence of spleen

• Blood products within 6 months prior to study entry

• Previous dengue virus or other flavivirus (e.g., yellow fever virus, St. Louis encephalitis, West Nile virus) infection

• Prior receipt of yellow fever or dengue vaccine (licensed or experimental)

• Plans to travel to an area where dengue infection is common

• Received an 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

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

Intervention

Biological:
• rDEN4delta30-4995
Live attenuated rDEN4delta30-4995 vaccine (one of three doses)
• Placebo
Placebo for rDEN4delta30-4995

Locations

Country	Name	City	State
United States	Vanderbilt University School of Medicine	Nashville	Tennessee

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)

Bhamarapravati N, Sutee Y. Live attenuated tetravalent dengue vaccine. Vaccine. 2000 May 26;18 Suppl 2:44-7. — View Citation

Blaney JE Jr, Durbin AP, Murphy BR, Whitehead SS. Development of a live attenuated dengue virus vaccine using reverse genetics. Viral Immunol. 2006 Spring;19(1):10-32. Review. — View Citation

Durbin AP, Karron RA, Sun W, Vaughn DW, Reynolds MJ, Perreault JR, Thumar B, Men R, Lai CJ, Elkins WR, Chanock RM, Murphy BR, Whitehead SS. Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3'-untranslated region. Am J Trop Med Hyg. 2001 Nov;65(5):405-13. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of vaccine-related adverse events, graded by severity for each dose		Throughout study	Yes
Primary	Immunogenicity of the rDEN4delta30-4995 vaccine against DEN4 virus by measurement of plaque reduction neutralization titers (PRNT)		At Days 28 and 42	No
Secondary	Durability of antibody responses to DEN4 virus		At Month 6	No
Secondary	Frequency, quantity, and duration of viremia in each dose cohort studied based on the mean peak viremia, mean day onset of viremia, and mean duration of viremia of each dose cohort		Throughout study	No
Secondary	Number of vaccinees infected with the rDEN4delta30-4995 chimeric vaccine		Throughout study	No