Evaluating the Safety and Effectiveness of a Dengue Virus Vaccine in Healthy Adults

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT02021968
First received: December 20, 2013
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

Dengue viruses can cause dengue illness ranging from a mild illness to life-threatening disease. The purpose of this study is to evaluate the protective effectiveness of a dengue virus vaccine in healthy adults.


Condition Intervention Phase
Dengue
Biological: TetraVax-DV-TV003
Biological: rDEN2∆30-7169
Biological: Placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Phase 1 Evaluation of the Protective Efficacy of a Single Dose of the Live Attenuated Tetravalent Dengue Vaccine TV003 to Protect Against Infection With Attenuated DENV-2, rDEN2∆30-7169

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Protection against viremia induced by rDEN2∆30, determined by rDEN2∆20-7169 titer [ Time Frame: Measured through Day 196 ] [ Designated as safety issue: Yes ]
    Participants will receive rDEN2∆30-7169 at Day 180. Viremia caused by rDEN2∆30-7160 will be measured through Day 196. Blood samples will be obtained from all participants on Days 180, 182, 184, 186, 188, 190, 192, 194, and 196, and the titer of rDEN2∆20-7169 will be determined.

  • Frequency of TV003 and rDEN2∆30-7169-related adverse events (AEs), as classified by both severity and seriousness, through active and passive surveillance [ Time Frame: Measured through participants' last study visit on Day 360 ] [ Designated as safety issue: Yes ]
  • Dengue virus neutralizing antibody titer [ Time Frame: Measured through participants' last study visit on Day 360 ] [ Designated as safety issue: No ]
    Seropositivity to each serotype will be defined as a PRNT50 of greater than or equal to 1:10 by Day 90 (TV003) and by Day 270 (rDEN2∆30-7169).


Other Outcome Measures:
  • Frequency of viremia following TV003 vaccination [ Time Frame: Measured through Day 16 visit ] [ Designated as safety issue: Yes ]
  • Quantity of viremia following TV003 vaccination [ Time Frame: Measured through Day 16 visit ] [ Designated as safety issue: Yes ]
  • Duration of viremia following TV003 vaccination [ Time Frame: Measured through Day 16 visit ] [ Designated as safety issue: Yes ]
  • Determine if peak neutralizing antibody (NAb) titer against DENV-2 following TV003 vaccination or NAb titer against DENV-2 measured at Day 180 correlates with protection against viremia, rash, and/or neutropenia following inoculation with rDEN2∆30-7169 [ Time Frame: Measured through Day 208 ] [ Designated as safety issue: Yes ]
    Neutralizing antibodies will be measured through Day 180 following vaccination with TV003; viremia, rash, and neutropenia elicited by DEN2∆30-7169 will be measured from Day 180 through Day 208


Estimated Enrollment: 48
Study Start Date: November 2013
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: TetraVax-DV-TV003 vaccine
Participants in this arm will receive a single injection of the TetraVax-DV-TV003 vaccine on Day 0 (study entry). On Day 180, participants will receive a single injection of the attenuated rDEN2∆30-7169 virus.
Biological: TetraVax-DV-TV003
TetraVax-DV-TV003 is a live attenuated recombinant tetravalent dengue virus vaccine, which will be administered as a 0.5 mL dose containing 10^3.0 plaque forming units (PFUs) each of DENV-1, DENV-2, DENV-3, and DENV-4. It will be delivered by subcutaneous injection in the deltoid region of the upper arm.
Other Name: TV003
Biological: rDEN2∆30-7169
The challenge virus, rDEN2∆30-7169, is a live recombinant attenuated DENV-2 candidate vaccine virus and will be administered as a 0.5 mL dose containing 10^3 PFUs of rDEN2∆30-7169. It will be delivered by subcutaneous injection in the deltoid region of the upper arm.
Placebo Comparator: Placebo
Participants in this arm will receive a single injection of placebo on Day 0 (study entry). On Day 180, participants will receive a single injection of the attenuated rDEN2∆30-7169 virus.
Biological: rDEN2∆30-7169
The challenge virus, rDEN2∆30-7169, is a live recombinant attenuated DENV-2 candidate vaccine virus and will be administered as a 0.5 mL dose containing 10^3 PFUs of rDEN2∆30-7169. It will be delivered by subcutaneous injection in the deltoid region of the upper arm.
Biological: Placebo
The placebo vaccine is the vaccine diluent 1X L-15, which will be administered as a 0.5 mL dose delivered by subcutaneous injection in the deltoid region of the upper arm.

Detailed Description:

There are 4 types of dengue virus (DENV-1, DENV-2, DENV-3, and DENV-4); each can cause dengue illness ranging from a mild illness to life-threatening disease. More than 2 billion persons in tropical and subtropical regions of the world are at risk for acquiring dengue, which is why development of a dengue vaccine is a top public health priority.

The purpose of this study is to evaluate the ability of a single dose of TetraVax-DV-TV003 (TV003) vaccine to protect against infection with rDEN2∆30, an attenuated candidate DENV-2 vaccine.

This study will enroll healthy adults with no history of previous infection with a flavivirus (any of a group of viruses that includes the dengue virus). Participants will be randomly assigned to receive either the TV003 vaccine or placebo vaccine on Day 0 (study entry). At Day 180, all participants will receive an injection of the "challenge" virus, rDEN2∆30, an attenuated (weakened) DENV-2 vaccine. For at least 30 minutes after each vaccination, participants will remain in the study clinic to be monitored for any adverse effects of the vaccines. Participants will record their temperature at least 3 times a day for 16 days after the first and second vaccinations.

In addition to vaccination visits at Day 0 and Day 180, participants will attend study visits at Day 2, 4, 6, 8, 10, 12, 14, 16, 21, 28, 56, 90, 150, 182, 184, 186, 188, 190, 192, 194, 196, 201, 208, 236, 270, and 360. At all study visits, participants will give a medical history and undergo a blood collection; at most study visits, participants will undergo a physical examination. Female participants will have a pregnancy test at select study visits.

  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 as determined by physical examination, laboratory screening, and review of medical history
  • Available for the duration of the study, approximately 26 weeks after second inoculation
  • Willingness to participate in the study as evidenced by signing the informed consent document
  • Females Only: Female participants of childbearing potential willing to use effective contraception. Reliable methods of contraception include: hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, intrauterine device, and abstinence (6 months or more since last sexual encounter). All female participants will be considered having child-bearing potential except for those with hysterectomy, tubal ligation, tubal coil (at least 3 months prior to vaccination), or post-menopausal status documented as at least 1 year since last menstrual period.

Exclusion Criteria:

  • Females Only: Currently pregnant, as determined by positive beta-human choriogonadotropin (HCG) test, breast-feeding
  • 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 ability of the participant to understand and cooperate with the requirements of the study protocol
  • Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine as defined in the study protocol.
  • Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the participant unable to comply with the protocol
  • Any significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by participant 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 28 days prior to or following vaccination. Immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg 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 28 days following vaccination
  • Asplenia
  • Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination
  • History or serologic evidence of previous dengue virus infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis virus, West Nile virus)
  • Previous receipt of a flavivirus vaccine (licensed or experimental)
  • Anticipated receipt of any investigational agent in the 28 days before or after vaccination
  • Participant 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 Second Vaccine

  • Good general health as determined by physical examination and review of medical history
  • Available for the duration of the study, approximately 26 weeks after the second dose
  • Willingness to participate in the study as evidenced by signing the informed consent document
  • Females Only: Female participants of childbearing potential willing to use effective contraception for the duration of the trial. Reliable methods of contraception include: hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, intrauterine device, and abstinence (6 months or more since last sexual encounter). All female participants will be considered having child-bearing potential except for those with hysterectomy, tubal ligation, tubal coil (at least 3 months prior to vaccination), or post-menopausal status documented as at least 1 year since last menstrual period.

Exclusion Criteria for Second Vaccine

  • Anaphylaxis or angioedema following the first dose of vaccine
  • Females Only: Currently pregnant, as determined by positive beta-HCG test, breast-feeding
  • 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 ability of the participant to understand and cooperate with the requirements of the study protocol
  • Day 150 laboratory values of Grade 1 or above for serum ALT and creatinine, as defined in the study protocol. More information on this criterion can be found in the protocol.
  • Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant participating in the trial or would render the participant unable to comply with the protocol
  • Any significant alcohol or drug abuse in the past 12 months which has caused medical, occupational, or family problems, as indicated by participant 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
  • HCV infection, by screening and confirmatory assays
  • HBV infection, by 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 greater than or equal to 10 mg 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 28 days following vaccination
  • Asplenia
  • Receipt of blood products within the past 6 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination
  • Anticipated receipt of any other investigational agent in the 28 days before or after vaccination
  • Participant has definite plans to travel to a dengue endemic area during the study
  • Refusal to allow storage of specimens for future research

Other Treatments and Ongoing Exclusion Criteria

The following criteria will be reviewed on Study Days 28 and 56 following each vaccination. If any become applicable during the study, the participant will not be included in further immunogenicity evaluations, as of the exclusionary visit. The participant will, however, be encouraged to remain in the study for safety evaluations for the duration of the study.

  • Use of any investigational drug or investigational vaccine other than the study vaccine during the 28-day period after vaccination
  • Chronic administration (14 days or longer) of steroids (defined as prednisone equivalent of greater than or equal to 10 mg per day), immunosuppressants, or other immune-modifying drugs initiated during the 28-day period after vaccination (topical and nasal steroids are allowed)
  • Receipt of a licensed vaccine during the 28-day period after vaccination
  • Receipt of immunoglobulins and/or any blood products during the 28-day period after vaccination
  • Pregnancy
  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: NCT02021968

Locations
United States, Maryland
Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health Recruiting
Baltimore, Maryland, United States, 21205
Contact: Cecilia Tibery, PAC    410-955-1622      
United States, Vermont
University of Vermont Vaccine Testing Center Recruiting
Burlington, Vermont, United States, 05405
Contact: Cathy Larsson, BA, CCRC    802-656-0013    VaccineTestingCenter@uvm.edu   
Sponsors and Collaborators
Investigators
Principal Investigator: Anna Durbin, MD Center for Immunization Research (CIR), Johns Hopkins School of Public Health
Principal Investigator: Beth Kirkpatrick, MD University of Vermont
  More Information

No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02021968     History of Changes
Other Study ID Numbers: CIR 287
Study First Received: December 20, 2013
Last Updated: June 23, 2014
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 August 01, 2014