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Safety and Immune Response to Two Doses of rDEN2/4delta30 Dengue Vaccine

Primary Purpose

Dengue Fever

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
rDEN2/4delta30(ME) vaccine
Placebo
Sponsored by
National Institute of Allergy and Infectious Diseases (NIAID)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Dengue Fever

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Good general health as determined by means of the screening procedures.
  • Available for the duration of the study (32 weeks for cohort 1 and 23 weeks for cohort 2)
  • Willing to use effective methods of contraception

Exclusion Criteria:

  • Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies
  • Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator will affect the ability of the volunteer to understand and cooperate with the requirements of the study protocol
  • Neutropenia as defined by an ANC ≤1500/mm3
  • ALT level above the laboratory-defined upper limit of normal
  • Serum creatinine level above the laboratory-defined upper limit of normal
  • Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol.
  • Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months
  • History of a severe allergic reaction or anaphylaxis
  • Severe asthma (emergency room visit or hospitalization within the last 6 months)
  • Positive HIV-1 serology by screening and confirmatory assays
  • Positive for hepatitis C virus (HCV) by screening and confirmatory assays
  • Positive hepatitis B surface antigen (HBsAg) by enzyme-linked immunosorbent assay (ELISA)
  • Known immunodeficiency syndrome
  • Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study
  • Receipt of a live vaccine within the 4 weeks or a killed vaccine within the 2 weeks prior to entry into the study
  • Has had spleen surgically removed
  • Receipt of blood products within the 6 months prior to study entry
  • History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g. yellow fever virus, St. Louis encephalitis, West Nile virus).
  • Previous receipt of yellow fever or dengue vaccine (licensed or experimental)
  • Persons who have received any investigational agent in the 30 days prior to study entry
  • Persons who have definite plans to travel to a dengue endemic area during the study

Sites / Locations

  • Center for Immunization Research

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

1

2

Arm Description

Participants will receive 1 injection of rDEN2/4delta30(ME) or placebo vaccine on Days 0 and 180

Participants will receive 1 injection of rDEN2/4delta30(ME) or placebo vaccine on Days 0 and 120

Outcomes

Primary Outcome Measures

Determine the frequency of vaccine related AEs for each dose, graded by severity.
Compare the immunogenicity of the two 2-dose regimens of the rDEN2/4Δ30(ME) candidate vaccine as assessed by neutralizing antibody titers to DEN2

Secondary Outcome Measures

Assess the frequency, quantity, and duration of viremia after each dose of vaccine.
Determine the number of vaccinees infected with rDEN2/4Δ30(ME)
Comparison of infectivity rates, safety, and immunogenicity between dose 1 and dose 2 withhin cohort and between cohorts
Evaluation of the phenotype and activation of peripheral blood mononuclear cells at primary infection and upon reinfection with the DEN2/4Δ30(ME) vaccine.

Full Information

First Posted
June 11, 2009
Last Updated
December 31, 2012
Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00920517
Brief Title
Safety and Immune Response to Two Doses of rDEN2/4delta30 Dengue Vaccine
Official Title
Safety and Immunogenicity of a 2-Dose Regimen of rDEN2/4Δ30 Dengue Vaccine With Boosting at 4 Versus 6 Months
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
January 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Dengue fever, caused by dengue viruses, is a major health problem in the 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.
Detailed Description
Dengue viruses, which cause dengue fever and dengue shock syndrome, are a major cause of morbidity and mortality in several of the world's tropical and subtropical regions. The rDEN2/4delta30(ME) vaccine is a live attenuated dengue virus vaccine that may be protective against dengue virus serotype 2 (DEN2). The purpose of this study is to evaluate the safety and immunogenicity of the rDEN2/4delta30(ME) vaccine in healthy adults. This study will last approximately 5 to 7 months with 25 study visits. Participants will be randomly assigned into one of two cohorts. Participants in Cohort 1 will receive an injection of rDEN2/4delta30(ME) or placebo vaccine at Days 0 and 180. Participants in Cohort 2 will receive an injection of rDEN2/4delta30(ME) or placebo vaccine at Days 0 and 120. Participants will be asked to record their temperature in a diary for 16 days after each vaccination. At each study visit a physical examination, symptom history, and blood and urine collection will occur.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue Fever

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Active Comparator
Arm Description
Participants will receive 1 injection of rDEN2/4delta30(ME) or placebo vaccine on Days 0 and 180
Arm Title
2
Arm Type
Active Comparator
Arm Description
Participants will receive 1 injection of rDEN2/4delta30(ME) or placebo vaccine on Days 0 and 120
Intervention Type
Biological
Intervention Name(s)
rDEN2/4delta30(ME) vaccine
Intervention Description
10^3 PFU dose
Intervention Type
Biological
Intervention Name(s)
Placebo
Intervention Description
placebo for rDEN2/4delta30(ME) vaccine
Primary Outcome Measure Information:
Title
Determine the frequency of vaccine related AEs for each dose, graded by severity.
Time Frame
Throughout study
Title
Compare the immunogenicity of the two 2-dose regimens of the rDEN2/4Δ30(ME) candidate vaccine as assessed by neutralizing antibody titers to DEN2
Time Frame
At 4 and 6 weeks after each vaccination
Secondary Outcome Measure Information:
Title
Assess the frequency, quantity, and duration of viremia after each dose of vaccine.
Time Frame
Throughout study
Title
Determine the number of vaccinees infected with rDEN2/4Δ30(ME)
Time Frame
Throughout study
Title
Comparison of infectivity rates, safety, and immunogenicity between dose 1 and dose 2 withhin cohort and between cohorts
Time Frame
Throughout study
Title
Evaluation of the phenotype and activation of peripheral blood mononuclear cells at primary infection and upon reinfection with the DEN2/4Δ30(ME) vaccine.
Time Frame
Throughout study

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Good general health as determined by means of the screening procedures. Available for the duration of the study (32 weeks for cohort 1 and 23 weeks for cohort 2) Willing to use effective methods of contraception Exclusion Criteria: Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator will affect the ability of the volunteer to understand and cooperate with the requirements of the study protocol Neutropenia as defined by an ANC ≤1500/mm3 ALT level above the laboratory-defined upper limit of normal Serum creatinine level above the laboratory-defined upper limit of normal Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol. Medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months History of a severe allergic reaction or anaphylaxis Severe asthma (emergency room visit or hospitalization within the last 6 months) Positive HIV-1 serology by screening and confirmatory assays Positive for hepatitis C virus (HCV) by screening and confirmatory assays Positive hepatitis B surface antigen (HBsAg) by enzyme-linked immunosorbent assay (ELISA) Known immunodeficiency syndrome Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study Receipt of a live vaccine within the 4 weeks or a killed vaccine within the 2 weeks prior to entry into the study Has had spleen surgically removed Receipt of blood products within the 6 months prior to study entry History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g. yellow fever virus, St. Louis encephalitis, West Nile virus). Previous receipt of yellow fever or dengue vaccine (licensed or experimental) Persons who have received any investigational agent in the 30 days prior to study entry Persons who have definite plans to travel to a dengue endemic area during the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anna Durbin, MD
Organizational Affiliation
Johns Hopkins Bloomberg School of Public Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Immunization Research
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
26383952
Citation
Katzelnick LC, Fonville JM, Gromowski GD, Bustos Arriaga J, Green A, James SL, Lau L, Montoya M, Wang C, VanBlargan LA, Russell CA, Thu HM, Pierson TC, Buchy P, Aaskov JG, Munoz-Jordan JL, Vasilakis N, Gibbons RV, Tesh RB, Osterhaus AD, Fouchier RA, Durbin A, Simmons CP, Holmes EC, Harris E, Whitehead SS, Smith DJ. Dengue viruses cluster antigenically but not as discrete serotypes. Science. 2015 Sep 18;349(6254):1338-43. doi: 10.1126/science.aac5017.
Results Reference
derived

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Safety and Immune Response to Two Doses of rDEN2/4delta30 Dengue Vaccine

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