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Trial record 7 of 11 for:    NIAID | Recruiting, Not yet recruiting, Available Studies | anthrax OR botulism OR plague OR pox OR tularemia OR Viral hemorrhagic fever OR Junin OR Machupo OR Guanarito OR Lassa OR Hanta OR Rift Valley OR Dengue OR Ebola OR Marburg

Evaluation of the Efficacy of the Live Attenuated Tetravalent Dengue Vaccine Against DENV-2 and DENV-3 Challenge

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ClinicalTrials.gov Identifier: NCT03416036
Recruitment Status : Recruiting
First Posted : January 30, 2018
Last Update Posted : February 2, 2018
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
The purpose of this study is to evaluate the ability of a single dose of a live attenuated recombinant tetravalent dengue vaccine (TetraVax-DV-TV003, referred to as TV003) to protect against infection with a controlled human infection strain of either DENV-2 (rDEN2Δ30-7169) or DENV-3 (rDEN3Δ30) in adults 18 to 50 years of age with no history of previous flavivirus infection.

Condition or disease Intervention/treatment Phase
Dengue Biological: TetraVax-DV-TV003 (TV003) Biological: rDEN2Δ30-7169 (DENV-2) Biological: rDEN3Δ30 (DENV-3) Biological: Placebo Phase 1

Detailed Description:

This study will evaluate the ability of a single dose of a live attenuated recombinant tetravalent dengue vaccine (TetraVax-DV-TV003, referred to as TV003) to protect against infection with a controlled human infection strain of either DENV-2 (rDEN2Δ30-7169) or DENV-3 (rDEN3Δ30) in adults 18 to 50 years of age with no history of previous flavivirus infection.

Participants will be randomly assigned to receive either TV003 or placebo at study entry (Day 0) and either rDEN2Δ30-7169 or rDEN3Δ30 on Day 28.

Study visits will occur on Days 0, 4, 6, 8, 10, 12, 14, 16, 21, 28, 32, 34, 36, 38, 40, 42, 44, 49, 56, 84, 118, and 208. Visits may include a physical examination and blood collection.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Evaluation of the Efficacy of the Live Attenuated Tetravalent Dengue Vaccine Against DENV-2 and DENV-3 Challenge
Actual Study Start Date : November 28, 2017
Estimated Primary Completion Date : October 31, 2018
Estimated Study Completion Date : June 30, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dengue
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Arm 1: TV003 + rDEN2Δ30-7169
Participants will receive a single dose of TV003 at study entry (Day 0) and rDEN2Δ30-7169 on Day 28.
Biological: TetraVax-DV-TV003 (TV003)
TV003 contains 10^3.3 plaque-forming units (PFU)/mL of rDEN1Δ30, 10^3.3 PFU/mL of rDEN2/4Δ30(ME), 10^3.3 PFU/mL of rDEN3Δ30/31-7164, and 10^3.3 PFU/mL of rDEN4Δ30. Administered by subcutaneous injection in the deltoid region of the upper arm
Biological: rDEN2Δ30-7169 (DENV-2)
Administered at a dose of 10^3 PFU/mL by subcutaneous injection in the deltoid region of the upper arm
Experimental: Arm 2: TV003 + rDEN3Δ30
Participants will receive a single dose of TV003 at study entry (Day 0) and rDEN3Δ30 on Day 28.
Biological: TetraVax-DV-TV003 (TV003)
TV003 contains 10^3.3 plaque-forming units (PFU)/mL of rDEN1Δ30, 10^3.3 PFU/mL of rDEN2/4Δ30(ME), 10^3.3 PFU/mL of rDEN3Δ30/31-7164, and 10^3.3 PFU/mL of rDEN4Δ30. Administered by subcutaneous injection in the deltoid region of the upper arm
Biological: rDEN3Δ30 (DENV-3)
Administered at a dose of 10^3 PFU/mL by subcutaneous injection in the deltoid region of the upper arm
Placebo Comparator: Arm 3: Placebo + rDEN2Δ30-7169
Participants will receive placebo at study entry (Day 0) and rDEN2Δ30-7169 on Day 28.
Biological: rDEN2Δ30-7169 (DENV-2)
Administered at a dose of 10^3 PFU/mL by subcutaneous injection in the deltoid region of the upper arm
Biological: Placebo
Administered by subcutaneous injection in the deltoid region of the upper arm
Placebo Comparator: Arm 4: Placebo + rDEN3Δ30
Participants will receive placebo at study entry (Day 0) and rDEN3Δ30 on Day 28.
Biological: rDEN3Δ30 (DENV-3)
Administered at a dose of 10^3 PFU/mL by subcutaneous injection in the deltoid region of the upper arm
Biological: Placebo
Administered by subcutaneous injection in the deltoid region of the upper arm



Primary Outcome Measures :
  1. Frequency of rDEN2Δ30-7160 viremia [ Time Frame: Measured through Month 1 ]
    Based on statistical analysis of laboratory evaluations

  2. Frequency of rDEN3Δ30 viremia [ Time Frame: Measured through Month 1 ]
    Based on statistical analysis of laboratory evaluations

  3. Occurrence of solicited local and general adverse events (AEs) [ Time Frame: Measured through Day 56 ]
    Evaluated using the Adverse Event Grading Table in the study protocol

  4. Occurrence of unsolicited AEs [ Time Frame: Measured through Day 56 ]
    Evaluated using the Adverse Event Grading Table in the study protocol

  5. Occurrence of serious adverse events (SAEs) [ Time Frame: Measured through Day 208 ]
    Evaluated using the Adverse Event Grading Table in the study protocol


Secondary Outcome Measures :
  1. Frequency of viremia after vaccination with TV003 [ Time Frame: Measured through Day 208 ]
    Based on statistical analysis of laboratory evaluations

  2. Number of TV003 recipients infected with vaccine virus DENV-1, DENV-2, DENV-3, and DENV-4 [ Time Frame: Measured through Day 208 ]
    As defined by recovery of vaccine virus from the blood or serum of a subject and/or seropositivity OR seroconversion to DENV

  3. Serum plaque reduction neutralization titer 50% (PRNT50) to DENV-1, DENV-2, DENV-3, and DENV-4 viruses [ Time Frame: Measured through Day 180 ]
    Determined by seropositivity and seroconversion frequencies



Information from the National Library of Medicine

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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:

  • Adult male or female between 18 and 50 years of age, inclusive.
  • Good general health as determined by physical examination, laboratory screening, and review of medical history.
  • Available for the duration of the study, which is approximately 28 weeks.
  • Willingness to participate in the study as evidenced by signing the informed consent document.
  • Females only: Female subjects of childbearing potential should be 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 (greater than or equal to 6 months since last sexual encounter). All female subjects will be considered as having childbearing potential, except for those who have had a hysterectomy, tubal ligation, or tubal coil (at least 3 months prior to vaccination), or are considered to be post-menopausal, as documented by at least 1 year since last menstrual period.

Exclusion Criteria:

  • Females only: Currently pregnant, as determined by positive β-human choriogonadotropin (HCG) test, or breast-feeding.
  • Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease based on history, physical examination, and/or laboratory studies.
  • Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the subject's ability 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 this protocol.
  • Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, or would render the subject unable to comply with the protocol.
  • Any significant alcohol or drug abuse in the past 12 months that has caused medical, occupational, or family problems, as indicated by subject history.
  • History of a severe allergic reaction or anaphylaxis.
  • Severe asthma (emergency room visit or hospitalization within the last 6 months).
  • HIV infection, as indicated by screening and confirmatory assays.
  • Hepatitis C virus (HCV) infection, as indicated by screening and confirmatory assays.
  • Hepatitis B virus (HBV) infection, as indicated by hepatitis B surface antigen (HBsAg) screening.
  • Any known immunodeficiency syndrome.
  • Current use of anticoagulant medications (this does not include anti-platelet medication such as aspirin or non-steroidal anti-inflammatory medications).
  • Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 28 days prior to or following vaccination. An immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg of a prednisone equivalent per day for greater than or equal to 14 days.
  • Receipt of a live vaccine within 28 days or a killed vaccine within 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, or West Nile virus). Subjects will also be screened for Zika virus if they have traveled to areas of South and Central America in the past 18 months that have reported Zika-virus transmission (per the Centers for Disease Control and Prevention Zika travel information).
  • Previous receipt of a flavivirus vaccine (licensed or experimental).
  • Anticipated receipt of any investigational agent in the 28 days before or after vaccination.
  • Definite plans to travel to a dengue-endemic area during the study.
  • Refusal to allow specimen storage for future research.

Inclusion Criteria for Challenge with rDEN2Δ30-7169 or rDEN3Δ30

  • Currently enrolled in the study.
  • Good general health as determined by physical examination and review of medical history.
  • Available for the duration of the study, which is approximately 24 weeks after challenge.
  • Willingness to participate in the study as evidenced by signing the informed consent document.
  • Females only: Female subjects of childbearing potential should be 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 (greater than or equal to 6 months since last sexual encounter). All female subjects will be considered as having childbearing potential, except for those who have had a hysterectomy, tubal ligation, or tubal coil (at least 3 months prior to vaccination), or who are considered to be post-menopausal, as documented by at least 1 year since last menstrual period.

Exclusion Criteria for rDEN3Δ30 or rDEN2Δ30-7169 Challenge:

  • Anaphylaxis or angioedema following TV003 administration.
  • Females only: Currently pregnant, as determined by positive β- HCG test, or breast-feeding.
  • Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease based on history, physical examination, and/or laboratory studies.
  • Behavioral, cognitive, or psychiatric disease that, in the opinion of the investigator, affects the subject's ability to understand and cooperate with the requirements of the study protocol.
  • Any other condition that, in the opinion of the investigator, would jeopardize the safety or rights of a subject participating in the trial, or would render the subject unable to comply with the protocol.
  • History of a severe allergic reaction or anaphylaxis.
  • Severe asthma (emergency room visit or hospitalization within the last 6 months).
  • Any known immunodeficiency syndrome.
  • Current use of anticoagulant medications (this does not include anti-platelet medication such as aspirin or non-steroidal anti-inflammatory medications).
  • Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 28 days prior to or following challenge. An immunosuppressive dose of corticosteroids is defined as greater than or equal to 10 mg of a prednisone equivalent per day for greater than or equal to 14 days.
  • Receipt of a live vaccine (other than TV003) within 28 days prior to challenge or the anticipated receipt of a live vaccine within 28 days after challenge.
  • Receipt of a killed vaccine within 14 days prior to challenge or anticipated receipt of a killed vaccine within 14 days following challenge.
  • 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 challenge.
  • Anticipated receipt of any other investigational agent in the 28 days before or after challenge.
  • Definite plans to travel to a dengue-endemic area during the study.
  • Refusal to allow specimen storage for future research.

Other Treatments and Ongoing Exclusion Criteria:

  • The following criteria will be reviewed on study day 28 following receipt of TV003 and at study days 28 and 56 following receipt of rDEN2Δ30-7169 or rDEN3Δ30. If any become applicable during the study, the subject will not be included in per-protocol immunogenicity evaluations, as of the exclusionary visit. The subject will, however, be encouraged to remain in the study for safety evaluations until 6 months following the last vaccination (or challenge) received. If the subject had samples obtained at one or more of the protocol-defined time points for immunogenicity, he/she will be included in the intention-to-treat immunogenicity analysis.
  • Use of any investigational drug or investigational vaccine other than the study vaccine during the 28-day post-inoculation period.
  • Chronic administration (greater than or equal to 14 days) of steroids (defined as a prednisone equivalent of greater than or equal to 10 mg per day), immunosuppressants, or other immune-modifying drugs initiated during the 28-day period post-inoculation (topical and nasal steroids are allowed).
  • Receipt of a licensed killed vaccine during the 14-day post-inoculation period.
  • Receipt of immunoglobulins and/or any blood products during the 28-day post-inoculation period.
  • Pregnancy (see clarifying language in the protocol) - If the pregnancy is terminated spontaneously or by therapeutic abortion, immunogenicity assessments will be done on blood samples obtained after the pregnancy is terminated.

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): NCT03416036


Locations
United States, Maryland
Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health Recruiting
Baltimore, Maryland, United States, 21205
Contact: Cecilia Tibery    877-863-1374    ctibery1@jhu.edu   
United States, Vermont
Vaccine Testing Center, University of Vermont Recruiting
Burlington, Vermont, United States, 05405
Contact: Patricia Lutton    802-656-0013    vaccinetestingcenter@med.uvm.edu   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
Principal Investigator: Anna Durbin, MD Johns Hopkins Bloomberg School of Public Health

Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03416036     History of Changes
Other Study ID Numbers: CIR 323
First Posted: January 30, 2018    Key Record Dates
Last Update Posted: February 2, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

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