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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00712803
First received: July 8, 2008
Last updated: December 31, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Dengue
Biological: rDEN3-3'D4delta30
Phase 1

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Safety and immunogenicity, as assessed by neutralizing antibody titers [ Time Frame: At 4 weeks and 6 weeks after vaccination ] [ Designated as safety issue: Yes ]
  • Frequency of vaccine related adverse events as graded by severity [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Frequency, quantity, and duration of viremia after a single dose of vaccine [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Number of vaccines infected with rDEN3-3'D4delta30 [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Infectivity rates, safety, and immunogenicity of a single dose of rDEN3-3'D4delta30 vaccine [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
  • Durability of antibody response [ Time Frame: At 26 Weeks after vaccination ] [ Designated as safety issue: No ]
  • Obtain an estimate for the Human Infectious Dose-50% (HID50) idf dose dependent infectivity is observed [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Enrollment: 29
Study Start Date: December 2008
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
One subcutaneous vaccination (10^3 dose of vaccine) of rDEN3-3'D4delta30 vaccine into the deltoid region of either arm.
Biological: rDEN3-3'D4delta30
Live attenuated 10^3 dose of rDEN3-3'D4delta30 vaccine.
Experimental: 2
One subcutaneous vaccination (10^5 dose of vaccine or placebo) of rDEN3-3'D4delta30 vaccine into the deltoid region of either arm OR one subcutaneous vaccination (10^1 dose of vaccine or placebo) of rDEN3-3'D4delta30 vaccine into the deltoid region of either arm.
Biological: rDEN3-3'D4delta30
Live attenuated 10^5 dose of rDEN3-3'D4delta30 vaccine.
Biological: rDEN3-3'D4delta30
Live attenuated 10^1 dose of rDEN3-3'D4delta30 vaccine.

Detailed 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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00712803

Locations
United States, District of Columbia
Center for Immunization Research, Johns Hopkins School of Public Health
Washington, District of Columbia, United States, 20037
United States, Maryland
Center for Immunization Research, Johns Hopkins University of Public Health
Baltimore, Maryland, United States, 21205
Sponsors and Collaborators
Investigators
Principal Investigator: Anna Durbin, MD Center for Immunization Research (CIR), Johns Hopkins School of Public Health
  More Information

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00712803     History of Changes
Other Study ID Numbers: CIR 252
Study First Received: July 8, 2008
Last Updated: December 31, 2012
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Dengue
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral

ClinicalTrials.gov processed this record on September 18, 2014