Safety of and Immune Response to a Dengue Virus Vaccine (rDEN3-3'Ddelta30) in Healthy Adults

Dengue Clinical Trial

Official title:

A Phase I Dose Comparison Study of the Safety and Immunogenicity of rDEN3-3'Ddelta30, a Live Attenuated Virus Vaccine Candidate for the Prevention of Dengue Serotype 3

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00712803
• Other study ID #: CIR 252
• Status: Completed
• Phase: Phase 1
• First received: July 8, 2008
• Last updated: December 31, 2012
• Start date: December 2008
• Est. completion date: September 2009

Study information

• Verified date: December 2012
• 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 of and immune response to a new dengue virus vaccine in healthy adults.

Description:

Dengue viruses cause dengue fever and 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 rDEN3-3'D4delta30. This vaccine is derived from rDEN4delta30, another dengue virus vaccine candidate that has been shown to be safe and immunogenic in Phase I and II trials in healthy adults.

There will be two groups in this study. Participants in Group 1 will be randomly assigned to receive rDEN3-3'D4delta30 vaccine or placebo at study entry. The dosing for Group 2 will be determined by a safety review of all participants in Group 1. If less than 90 % of the Group 1 participants seroconvert to DEN3 participants in Group 2 will receive a higher dose of rDEN3-3'D4delta30. If at least 90 % of Group 1 participants seroconvert to DEN3, participants in Group 2 will receive a lower dose of rDEN3-3'D4delta30.

All participants will be required to monitor their temperature three times each day for the first 16 days following each vaccination. Study visits will occur 30 minutes following each vaccination and every other day after vaccination until Day 16, followed by four additional visits at selected days through Day 180. Blood collection, vital signs measurement, 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: 29
• Est. completion date: September 2009
• Est. primary completion date: September 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• General good health

• Available for the duration of the study

• Willing to use accepted forms of contraception

Exclusion Criteria:

• Clinically significant neurologic, heart, lung, liver, rheumatologic, autoimmune, or kidney disease by history, physical examination, or laboratory studies including urinalysis

• Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, may interfere with the study

• Certain abnormal laboratory values. More information on this criterion can be found in the protocol.

• Medical, work, or family problems as a result of alcohol or illegal drug use within 12 months of study entry

• History of severe allergy or anaphylaxis

• Severe asthma requiring an emergency room visit or hospitalization within 6 months of study entry

• HIV infected

• Hepatitis C virus infected

• Hepatitis B surface antibody positive

• Known immunodeficiency syndrome

• Use of corticosteroids or immunosuppressive drugs 30 days prior to study entry. Participants who have used topical or nasal corticosteroids are not excluded.

• Receipt of live vaccine within 4 weeks of study entry

• Receipt of killed vaccine within 2 weeks of study entry

• Absence of spleen

• Plan to travel to an area where dengue virus is common

• Any investigational product within 30 days of study entry

• Other condition that, in the opinion of the investigator, would interfere with the study

• Pregnancy or breastfeeding

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Dengue

Intervention

Biological:
• rDEN3-3'D4delta30
Live attenuated 10^3 dose of rDEN3-3'D4delta30 vaccine.
• rDEN3-3'D4delta30
Live attenuated 10^5 dose of rDEN3-3'D4delta30 vaccine.
• rDEN3-3'D4delta30
Live attenuated 10^1 dose of rDEN3-3'D4delta30 vaccine.

Locations

Country	Name	City	State
United States	Center for Immunization Research, Johns Hopkins University of Public Health	Baltimore	Maryland
United States	Center for Immunization Research, Johns Hopkins School of Public Health	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Blaney JE Jr, Hanson CT, Firestone CY, Hanley KA, Murphy BR, Whitehead SS. Genetically modified, live attenuated dengue virus type 3 vaccine candidates. Am J Trop Med Hyg. 2004 Dec;71(6):811-21. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and immunogenicity, as assessed by neutralizing antibody titers		At 4 weeks and 6 weeks after vaccination	Yes
Primary	Frequency of vaccine related adverse events as graded by severity		Throughout study	Yes
Secondary	Frequency, quantity, and duration of viremia after a single dose of vaccine		Throughout study	Yes
Secondary	Number of vaccines infected with rDEN3-3'D4delta30		Throughout study	Yes
Secondary	Infectivity rates, safety, and immunogenicity of a single dose of rDEN3-3'D4delta30 vaccine		Throughout study	Yes
Secondary	Durability of antibody response		At 26 Weeks after vaccination	No
Secondary	Obtain an estimate for the Human Infectious Dose-50% (HID50) idf dose dependent infectivity is observed		Throughout study	No