Safety of and Immune Response of a 2-dose Regimen of rDEN1delta30 Dengue Virus Vaccine

This study has been completed.
Sponsor:
Collaborator:
Johns Hopkins Bloomberg School of Public Health
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00473135
First received: May 11, 2007
Last updated: January 11, 2010
Last verified: January 2008
  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 1

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


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
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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
Experimental: 2
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
Placebo Comparator: 3
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
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: NCT00473135

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

Publications:
Responsible Party: Anna Durbin, MD, Center for Immunization Research, Johns Hopkins School of Public Health
ClinicalTrials.gov Identifier: NCT00473135     History of Changes
Other Study ID Numbers: CIR 229, WIRB Protocol Number 20070718
Study First Received: May 11, 2007
Last Updated: January 11, 2010
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:
Dengue
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral

ClinicalTrials.gov processed this record on September 14, 2014