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Evaluation of the Safety and Immune Response of Five Admixtures of a Tetravalent Dengue Virus Vaccine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01072786
Recruitment Status : Completed
First Posted : February 22, 2010
Last Update Posted : January 3, 2013
Sponsor:
Collaborator:
Johns Hopkins Bloomberg School of Public Health
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Description
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Brief Summary:
Dengue viruses can cause dengue fever and other serious health conditions, primarily affecting people living in tropical regions of the world. This study will evaluate the safety and immune responses of five formulations of a tetravalent dengue virus vaccine in healthy adults.

Condition or disease Intervention/treatment Phase
Dengue Biological: TetraVax-DV Vaccine-Admixture 1 Biological: TetraVax-DV Vaccine-Admixture 2 Biological: TetraVax-DV Vaccine-Admixture 3 Biological: TetraVax-DV Vaccine-Admixture 4 Biological: Placebo Biological: TetraVax-DV Vaccine-Admixture 5 Phase 1

Detailed Description:

Dengue viruses cause dengue fever and the more severe condition, dengue hemorrhagic fever/shock syndrome. Dengue viruses are common in most tropical and subtropical regions of the world and infection with dengue viruses is the leading cause of hospitalization and death in children in many tropical Asian countries. For these reasons, the World Health Organization (WHO) has made the development of a dengue virus vaccine a top priority. This study will evaluate the safety and immunogenicity of five versions of a live, attenuated, tetravalent dengue virus vaccine called TetraVax-DV.

This study will enroll healthy adults 18-50 years old. Participants will be randomly assigned to receive one of the five versions of TetraVax-DV or placebo. At the vaccination study visit, participants will undergo a medical history review, physical examination, blood and urine collection, and vital sign measurements. Participants will then receive one injection of their assigned vaccine or placebo in the upper arm. After receiving the vaccine, participants will remain in the clinic for 30 minutes for observation. At home, participants will monitor and record their temperature three times a day for 16 days. Additional study visits will occur at Days 2, 4, 6, 8, 10, 12, 14, 16, 21, 28, 42, and 180 for physical exams, assessment of symptoms, and blood and urine collection. Some participants will attend an additional study visit at Day 60.

Participants who received one of the five versions of the vaccine will be asked to take part in an optional substudy that will evaluate the safety and immunogenicity of a second vaccination 6 months after the first vaccination. In the substudy, participants will be randomly assigned to receive either the same vaccine they received in the first part of the study or a placebo vaccine. For 6 months following the second vaccination, participants will attend study visits and take part in the same study procedures that occurred in the first part of the study.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 141 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 1 Evaluation of the Safety and Immunogenicity of Five Admixtures of TetraVax-DV, a Recombinant Live Attenuated Tetravalent Dengue Virus Vaccine, in Healthy Flavivirus-naïve Adult Subjects
Study Start Date : July 2010
Actual Primary Completion Date : June 2012
Actual Study Completion Date : June 2012

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: TetraVax-DV Vaccine-Admixture 1
Participants will receive the TetraVax-DV admixture 1 vaccine.
 Biological: TetraVax-DV Vaccine-Admixture 1
One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 1 (10^3 PFU of rDEN1Δ30, 10^3 PFU of rDEN2/4Δ30[ME], 10^3 PFU of rDEN3-3´D4Δ30, 10^3 PFU of rDEN4Δ30)
Experimental: TetraVax-DV Vaccine-Admixture 2
Participants will receive the TetraVax-DV admixture 2 vaccine.
 Biological: TetraVax-DV Vaccine-Admixture 2
One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 2 (10^3 PFU of rDEN1Δ30, 10^3 PFU of rDEN2/4Δ30[ME], 10^3 PFU of rDEN3-3´D4Δ30, 10^3 PFU of rDEN4Δ30-200,201)
Experimental: TetraVax-DV Vaccine-Admixture 3
Participants will receive the TetraVax-DV admixture 3 vaccine.
 Biological: TetraVax-DV Vaccine-Admixture 3
One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 3 (10^3 PFU of rDEN1Δ30, 10^3 PFU of rDEN2/4Δ30[ME], 10^3 PFU of rDEN3Δ30/31-7164, 10^3 PFU of rDEN4Δ30)
Experimental: TetraVax-DV Vaccine-Admixture 4
Participants will receive the TetraVax-DV admixture 4 vaccine.
 Biological: TetraVax-DV Vaccine-Admixture 4
One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 4 (10^3 PFU of rDEN1Δ30, 10^3 PFU of rDEN2/4Δ30[ME], 10^3 PFU of rDEN3Δ30/31-7164, 10^3 PFU of rDEN4Δ30-200,201)
Placebo Comparator: Placebo
Participants will receive the placebo.
 Biological: Placebo
One subcutaneous injection of a placebo containing vaccine diluent but no actual vaccine
Experimental: TetraVax-DV Vaccine-Admixture 5
Participants will receive the TetraVax-DV admixture 5 vaccine.
 Biological: TetraVax-DV Vaccine-Admixture 5
One subcutaneous injection of a recombinant live attenuated TetraVax-DV vaccine, admixture 5 (10^3 PFU of rDEN1Δ30, 10^4 PFU of rDEN2/4Δ30(ME), 10^3 PFU of rDEN3Δ30/31-7164, and 10^3 PFU of rDEN4Δ30)


Outcome Measures
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Primary Outcome Measures :
  1. Safety of five TetraVax-DV admixtures, as assessed by the frequency of vaccine-related adverse events (AEs), graded by severity [ Time Frame: Measured out to Day 28 ]
  2. Determination of the serum plaque reduction neutralization titer 60% (PRNT_60) to DEN1, DEN2, DEN3, and DEN4 viruses [ Time Frame: Measured at Days 0, 28, 42, and 180 ]
  3. Monovalent, bivalent, trivalent, and tetravalent seropositivity and seroconversion rates [ Time Frame: Measured at 4 and 6 weeks after vaccination ]
  4. Seropositivity and seroconversion rates to greater than 60% in in the TetraVax-DV admixture 5 vaccine arm [ Time Frame: Measured by Day 42 ]

Secondary Outcome Measures :
  1. Frequency, quantity, and duration of viremia following vaccination [ Time Frame: Measured out to Day 21 ]
  2. Number of vaccinees infected with DEN1, DEN2, DEN3, and DEN4 [ Time Frame: Measured by Day 42 ]
  3. Duration of the neutralizing antibody response [ Time Frame: Measured at Day 180 ]
  4. Safety and immunogenicity of a second dose of vaccine given 6 months after the first dose (optional substudy) [ Time Frame: Measured at Day 222 (42 days after second dose) ]
  5. Seroconversion as assessed by a greater than or equal to 4-fold rise in DEN1, DEN2, DEN3, or DEN4 neutralizing antibody titers compared with the pre-vaccination antibody titer [ Time Frame: Measured by Day 42 ]
  6. Seropositivity as assessed by PRNT_60 to DEN1, DEN2, DEN3, DEN4 greater than or equal to 1:10 compared with the pre-vaccination titer [ Time Frame: Measured by Day 42 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • In good general health, as determined by physical examination, laboratory screening, and review of medical history
  • Available for the duration of the study, approximately 26 weeks post-vaccination
  • Willing to participate in the study as evidenced by signing the informed consent document
  • Female participants of childbearing potential must be willing to use effective contraception for the duration of the trial. More information on this criterion can be found in the protocol.

Exclusion Criteria:

  • Pregnant or breastfeeding
  • 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 affects the person's ability to understand and cooperate with the requirements of the study
  • Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in the protocol
  • Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a person participating in the study or would render the person unable to comply with the study
  • Any significant alcohol or drug abuse in the 12 months before study entry which has caused medical, occupational, or family problems, as indicated by medical history
  • History of a severe allergic reaction or anaphylaxis
  • Severe asthma (emergency room visit or hospitalization in the 6 months before study entry)
  • HIV infection, by screening and confirmatory assays
  • Hepatitis C virus (HCV) infection, by screening and confirmatory assays
  • Hepatitis B virus (HBV) infection, by Hepatitis B surface antigen (HBsAg) screening
  • Any known immunodeficiency syndrome
  • Use of anticoagulant medications
  • Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 42 days prior to or following vaccination; immunosuppressive dose of corticosteroids is defined as 10 mg or more of prednisone equivalent per day for 14 days or longer
  • Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 42 days following vaccination
  • Absence of spleen
  • Receipt of blood products in the 6 months before study entry, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 42 days following vaccination
  • 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 a flavivirus vaccine (licensed or experimental)
  • Anticipated receipt of any investigational agent in the 42 days before or after vaccination
  • Has definite plans to travel to a dengue endemic area during the study
  • Refusal to allow storage of specimens for future research

Inclusion Criteria for Substudy:

  • Receipt of vaccine at first vaccination
  • In good general health, as determined by physical examination and review of medical history
  • Available for the duration of the study, approximately 6 months post-vaccination
  • Willing to participate in the study as evidenced by signing the informed consent document
  • Female participants of childbearing potential must be willing to use effective contraception for the duration of the trial. More information on this criterion can be found in the protocol.

Exclusion Criteria for Substudy:

  • Pregnant or breastfeeding
  • 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 affects the person's ability to understand and cooperate with the requirements of the study
  • Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a person participating in the study or would render the person unable to comply with the study
  • Any significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by medical history
  • History of a severe allergic reaction or anaphylaxis
  • Severe asthma (emergency room visit or hospitalization within the last 6 months)
  • HIV infection, by screening and confirmatory assays
  • Hepatitis C virus (HCV) infection, by screening and confirmatory assays
  • Hepatitis B virus (HBV) infection, by Hepatitis B surface antigen (HBsAg) screening
  • Any known immunodeficiency syndrome
  • Use of anticoagulant medications
  • Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 42 days prior to or following vaccination; immunosuppressive dose of corticosteroids is defined as 10 mg or more of prednisone equivalent per day for 14 days or longer
  • Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 42 days following vaccination
  • Absence of spleen
  • Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 42 days following vaccination
  • Anticipated receipt of any other investigational agent in the 42 days before or after vaccination
  • Has definite plans to travel to a dengue endemic area during the study
  • Refusal to allow storage of specimens for future research
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01072786


Locations
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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 School of Public Health
Baltimore, Maryland, United States, 21205
United States, Vermont
Fletcher Allen Health Care (FAHC), General Clinical Research Center (GCRC)
Burlington, Vermont, United States, 05401
University of Vermont Vaccine Testing Center
Burlington, Vermont, United States, 05401
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Johns Hopkins Bloomberg School of Public Health
Investigators
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Principal Investigator: Anna Durbin, MD Center for Immunization Research (CIR), Johns Hopkins School of Public Health
More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01072786    
Other Study ID Numbers: CIR 268
First Posted: February 22, 2010    Key Record Dates
Last Update Posted: January 3, 2013
Last Verified: December 2012
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Dengue Virus
Dengue Fever
Dengue Vaccine
Dengue Hemorrhagic Fever
Dengue Shock Syndrome
Additional relevant MeSH terms:
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Dengue
Arbovirus Infections
Vector Borne Diseases
Infections
Virus Diseases
Flavivirus Infections
 Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral
Vaccines
Immunologic Factors
Physiological Effects of Drugs