<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02186626</url>
  </required_header>
  <id_info>
    <org_study_id>CIR 290</org_study_id>
    <secondary_id>WIRB/20140078</secondary_id>
    <nct_id>NCT02186626</nct_id>
  </id_info>
  <brief_title>Evaluating the Safety and Immunogenicity of a Live Attenuated West Nile Virus Vaccine for West Nile Encephalitis in Adults 50 to 65 Years of Age</brief_title>
  <official_title>Phase 1 Study of the Safety and Immunogenicity of a 2-Dose Regimen of West Nile/Dengue 4-3´Δ30 Chimeric Virus Vaccine (WN/DEN4Δ30), a Live Attenuated Vaccine for West Nile Encephalitis, in Flavivirus-naïve Adults 50-65 Years of Age</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Institute of Allergy and Infectious Diseases (NIAID)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      West Nile virus (WNV) is considered an emerging virus in the United States, and infection can&#xD;
      lead to severe illness in older adults. This study will evaluate the safety of and immune&#xD;
      response to a live West Nile virus vaccine (WN/DEN4Δ30) for the prevention of West Nile&#xD;
      encephalitis in adults 50 to 65 years old.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      WNV is the leading vector-borne cause of viral encephalitis in the United States. Severe&#xD;
      illness is most common in older adults, and in this population, the virus can cause&#xD;
      hepatitis, meningitis, and encephalitis leading to paralysis, coma, and death. WNV illness is&#xD;
      a public health issue and is an emerging disease in the United States. This study will&#xD;
      evaluate the safety and immunogenicity of a live attenuated West Nile/dengue chimeric virus&#xD;
      vaccine (WN/DEN4Δ30) for the prevention of West Nile encephalitis in adults 50 to 65 years&#xD;
      old.&#xD;
&#xD;
      This study will enroll healthy adults, 50 to 65 years old, who have no history of previous&#xD;
      flavivirus infection. Participants will be randomly assigned to receive the WN/DEN4Δ30&#xD;
      vaccine or placebo vaccine at study entry (Day 0). At the entry visit, participants will&#xD;
      undergo a medical history review, physical examination, blood collection, and vital sign&#xD;
      measurements; female participants will also take a pregnancy test. Participants will then&#xD;
      receive their assigned vaccine, and they will remain in the clinic for 30 minutes after the&#xD;
      vaccination for monitoring. Participants will record their temperature and symptoms 3 times a&#xD;
      day for 16 days after each vaccination. Additional study visits will occur on Days 3, 6, 8,&#xD;
      10, 12, 14, 16, 21, 28, 56, 90, and 150. These visits may include the same study procedures&#xD;
      that occurred at the entry visit. At a study visit on Day 180, participants will receive&#xD;
      another dose of their assigned vaccine. Additional study visits will occur on Days 183, 186,&#xD;
      188, 190, 192, 194, 196, 201, 208, 236, 270, and 360. All study procedures after the second&#xD;
      vaccination will be the same that occurred after the first vaccination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2014</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of vaccine-related adverse events (AEs)</measure>
    <time_frame>Measured through Day 360</time_frame>
    <description>As classified by both intensity and severity through active and passive surveillance</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Measurement of anti-WNV neutralizing antibody</measure>
    <time_frame>Measured through Day 360</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">28</enrollment>
  <condition>West Nile Virus</condition>
  <arm_group>
    <arm_group_label>WN/DEN4Δ30 Vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive one dose of the WN/DEN4Δ30 vaccine at study entry and one dose at Day 180.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive one dose of the placebo at study entry and one dose at Day 180.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>WN/DEN4Δ30 Vaccine</intervention_name>
    <description>WN/DEN4Δ30 vaccine is a live attenuated, recombinant, chimeric virus. Dose: 10^4 plaque-forming units (PFUs); delivered by subcutaneous injection in the deltoid region of the upper arm.</description>
    <arm_group_label>WN/DEN4Δ30 Vaccine</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Delivered by subcutaneous injection in the deltoid region of the upper arm.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult males and non-pregnant, non-breastfeeding females between 50 and 65 years of&#xD;
             age, inclusive. Children will not be recruited or enrolled in this study for safety&#xD;
             considerations.&#xD;
&#xD;
          -  Good general health, as determined by means of the screening procedures&#xD;
&#xD;
          -  Available for the duration of the trial&#xD;
&#xD;
          -  Willingness to participate in the study as evidenced by signing the informed consent&#xD;
             form (ICF)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy, as determined by positive beta-human choriogonadotropin (HCG) test (if&#xD;
             female)&#xD;
&#xD;
          -  Currently lactating and breastfeeding (if female)&#xD;
&#xD;
          -  Participant is unwilling to use reliable contraception methods for the duration of the&#xD;
             trial (reliable methods of birth control include: pharmacologic contraceptives&#xD;
             including oral, parenteral, and transcutaneous delivery; condoms with spermicide;&#xD;
             diaphragm with spermicide; surgical sterilization; intrauterine device; abstinence;&#xD;
             and post-menopausal documented for at least 1 year). All female participants will be&#xD;
             considered as having childbearing potential except for those with documented&#xD;
             hysterectomy, tubal ligation, tubal coil (at least 3 months prior to vaccination), or&#xD;
             who are post-menopausal for at least 1 year since last menstrual period.&#xD;
&#xD;
          -  Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,&#xD;
             rheumatologic, autoimmune, or renal disease by history, physical examination, and/or&#xD;
             laboratory studies&#xD;
&#xD;
          -  Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator&#xD;
             affects the ability of the participant to understand and cooperate with the study&#xD;
             protocol&#xD;
&#xD;
          -  Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC),&#xD;
             alanine aminotransferase (ALT), and serum creatinine, as defined in this protocol&#xD;
&#xD;
          -  Other condition that in the opinion of the investigator would jeopardize the safety or&#xD;
             rights of a participant in the trial or would render the participant unable to comply&#xD;
             with the protocol&#xD;
&#xD;
          -  Participant has had medical, occupational, or family problems as a result of alcohol&#xD;
             or illicit drug use during the past 12 months&#xD;
&#xD;
          -  History of a severe allergic reaction or anaphylaxis&#xD;
&#xD;
          -  Severe asthma (emergency room visit or hospitalization within the last 6 months)&#xD;
&#xD;
          -  Positive HIV-1 serology by screening and confirmatory assays&#xD;
&#xD;
          -  Positive for hepatitis C virus (HCV) by screening and confirmatory assays&#xD;
&#xD;
          -  Hepatitis B virus (HBV) infection, by positive hepatitis B surface antigen (HBsAg)&#xD;
&#xD;
          -  Any confirmed or suspected immunosuppressive or immune modulating disorder (e.g.,&#xD;
             asplenia, lupus, rheumatoid arthritis, vasculitis, scleroderma, and diabetes mellitus)&#xD;
&#xD;
          -  Chronic administration (greater than or equal to 14 days) of steroids (defined as&#xD;
             prednisone equivalent of greater than or equal to 10 mg per day), immunosuppressants,&#xD;
             or other immune-modifying drugs initiated during the 28-day period post-vaccination&#xD;
             (topical and nasal steroids are allowed)&#xD;
&#xD;
          -  Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior&#xD;
             to vaccination or anticipated receipt of any vaccine during the 28 days following&#xD;
             vaccination&#xD;
&#xD;
          -  History of a surgical splenectomy&#xD;
&#xD;
          -  Receipt of blood products within the past 3 months, including transfusions or&#xD;
             immunoglobulin, or anticipated receipt of any blood products or immunoglobulin during&#xD;
             the 28 days following vaccination&#xD;
&#xD;
          -  History or serologic evidence of previous WNV infection or other flavivirus infection&#xD;
             (e.g., yellow fever virus, St. Louis encephalitis virus, and dengue virus)&#xD;
&#xD;
          -  Previous receipt of yellow fever, WNV, or dengue vaccine (licensed or investigational)&#xD;
&#xD;
          -  Receipt of any investigational agent in the past 28 days or anticipation of receipt of&#xD;
             any investigational agent within 28 days following vaccination&#xD;
&#xD;
          -  Refusal to allow storage of specimens for future research&#xD;
&#xD;
        Inclusion Criteria for Second Dose:&#xD;
&#xD;
          -  Good general health, as determined by physical examination and review of medical&#xD;
             history&#xD;
&#xD;
          -  Available for the duration of the study, approximately 26 weeks after the second dose&#xD;
&#xD;
          -  Ongoing willingness to participate in the study&#xD;
&#xD;
          -  Females only: female participants of childbearing potential willing to use effective&#xD;
             contraception for the duration of the trial. Reliable methods of contraception&#xD;
             include: hormonal birth control, condoms with spermicide, diaphragm with spermicide,&#xD;
             surgical sterilization, intrauterine device, and abstinence (greater than 6 months&#xD;
             since last sexual encounter). All female participants will be considered as having&#xD;
             childbearing potential except for those with documented hysterectomy, tubal ligation,&#xD;
             tubal coil (at least 3 months prior to vaccination), or who are post-menopausal for&#xD;
             least 1 year since last menstrual period.&#xD;
&#xD;
        Exclusion Criteria for Second Dose:&#xD;
&#xD;
          -  Anaphylaxis or angioedema following the first dose of vaccine&#xD;
&#xD;
          -  Females only: currently pregnant, as determined by positive beta-HCG test, or&#xD;
             breastfeeding&#xD;
&#xD;
          -  Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,&#xD;
             rheumatologic, autoimmune, or renal disease by history, physical examination, and/or&#xD;
             laboratory studies&#xD;
&#xD;
          -  Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator&#xD;
             affects the ability of the participant to understand and cooperate with the&#xD;
             requirements of the study protocol&#xD;
&#xD;
          -  Any other condition that in the opinion of the investigator would jeopardize the&#xD;
             safety or rights of a participant in the trial or would render the participant unable&#xD;
             to comply with the protocol&#xD;
&#xD;
          -  Any significant alcohol or drug abuse in the past 12 months that has caused medical,&#xD;
             occupational, or family problems, as indicated by participant history&#xD;
&#xD;
          -  History of a severe allergic reaction or anaphylaxis&#xD;
&#xD;
          -  Severe asthma (emergency room visit or hospitalization within the last 6 months)&#xD;
&#xD;
          -  HIV infection, by screening and confirmatory assays&#xD;
&#xD;
          -  HCV infection, by screening and confirmatory assays&#xD;
&#xD;
          -  HBV infection, by HBsAg screening&#xD;
&#xD;
          -  Any confirmed or suspected immunosuppressive or immune modulating disorder (e.g.,&#xD;
             asplenia, lupus, rheumatoid arthritis, vasculitis, scleroderma, or diabetes mellitus)&#xD;
&#xD;
          -  Current use of anticoagulant medications&#xD;
&#xD;
          -  Chronic administration (greater than or equal to 14 days) of steroids (defined as&#xD;
             prednisone equivalent of greater than or equal to 10 mg per day), immunosuppressants,&#xD;
             or other immune-modifying drugs initiated during the 28-day period post-vaccination&#xD;
             (topical and nasal steroids are allowed)&#xD;
&#xD;
          -  Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior&#xD;
             to vaccination or anticipated receipt of any vaccine during the 28 days following&#xD;
             vaccination&#xD;
&#xD;
          -  History of surgical splenectomy&#xD;
&#xD;
          -  Receipt of blood products within the past 3 months, including transfusions or&#xD;
             immunoglobulin or anticipated receipt of any blood products or immunoglobulin during&#xD;
             the 28 days following vaccination&#xD;
&#xD;
          -  Receipt of any other investigational agent in the 28 days before vaccination or&#xD;
             anticipated within 28 days following vaccination&#xD;
&#xD;
          -  Refusal to allow storage of specimens for future research&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Anna Durbin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins Bloomberg School of Public Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Immunization Research (CIR), Johns Hopkins Bloomberg School of Public Health</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vaccine Testing Center, University of Vermont College of Medicine (UVM)</name>
      <address>
        <city>Burlington</city>
        <state>Vermont</state>
        <zip>05401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Durbin AP, Wright PF, Cox A, Kagucia W, Elwood D, Henderson S, Wanionek K, Speicher J, Whitehead SS, Pletnev AG. The live attenuated chimeric vaccine rWN/DEN4Delta30 is well-tolerated and immunogenic in healthy flavivirus-naive adult volunteers. Vaccine. 2013 Nov 19;31(48):5772-7. doi: 10.1016/j.vaccine.2013.07.064. Epub 2013 Aug 19.</citation>
    <PMID>23968769</PMID>
  </reference>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 10, 2014</study_first_posted>
  <last_update_submitted>January 31, 2017</last_update_submitted>
  <last_update_submitted_qc>January 31, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">February 1, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>West Nile Virus, vaccine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Encephalitis</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02186626
org study id: CIR 290
secondary id: WIRB/20140078
nct id: NCT02186626
lead sponsor: 
has dmc: Yes
West Nile virus (WNV) is considered an emerging virus in the United States, and infection can
      lead to severe illness in older adults. This study will evaluate the safety of and immune
      response to a live West Nile virus vaccine (WN/DEN4Δ30) for the prevention of West Nile
      encephalitis in adults 50 to 65 years old.
WNV is the leading vector-borne cause of viral encephalitis in the United States. Severe
      illness is most common in older adults, and in this population, the virus can cause
      hepatitis, meningitis, and encephalitis leading to paralysis, coma, and death. WNV illness is
      a public health issue and is an emerging disease in the United States. This study will
      evaluate the safety and immunogenicity of a live attenuated West Nile/dengue chimeric virus
      vaccine (WN/DEN4Δ30) for the prevention of West Nile encephalitis in adults 50 to 65 years
      old.

      This study will enroll healthy adults, 50 to 65 years old, who have no history of previous
      flavivirus infection. Participants will be randomly assigned to receive the WN/DEN4Δ30
      vaccine or placebo vaccine at study entry (Day 0). At the entry visit, participants will
      undergo a medical history review, physical examination, blood collection, and vital sign
      measurements; female participants will also take a pregnancy test. Participants will then
      receive their assigned vaccine, and they will remain in the clinic for 30 minutes after the
      vaccination for monitoring. Participants will record their temperature and symptoms 3 times a
      day for 16 days after each vaccination. Additional study visits will occur on Days 3, 6, 8,
      10, 12, 14, 16, 21, 28, 56, 90, and 150. These visits may include the same study procedures
      that occurred at the entry visit. At a study visit on Day 180, participants will receive
      another dose of their assigned vaccine. Additional study visits will occur on Days 183, 186,
      188, 190, 192, 194, 196, 201, 208, 236, 270, and 360. All study procedures after the second
      vaccination will be the same that occurred after the first vaccination.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Frequency of vaccine-related adverse events (AEs)
time frame: Measured through Day 360
description: As classified by both intensity and severity through active and passive surveillance
measure: Measurement of anti-WNV neutralizing antibody
time frame: Measured through Day 360
arm group label: WN/DEN4Δ30 Vaccine
arm group type: Experimental
description: Participants will receive one dose of the WN/DEN4Δ30 vaccine at study entry and one dose at Day 180.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will receive one dose of the placebo at study entry and one dose at Day 180.
intervention type: Biological
intervention name: WN/DEN4Δ30 Vaccine
description: WN/DEN4Δ30 vaccine is a live attenuated, recombinant, chimeric virus. Dose: 10^4 plaque-forming units (PFUs); delivered by subcutaneous injection in the deltoid region of the upper arm.
arm group label: WN/DEN4Δ30 Vaccine
intervention type: Biological
intervention name: Placebo
description: Delivered by subcutaneous injection in the deltoid region of the upper arm.
arm group label: Placebo
criteria: 
gender: All
minimum age: 50 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Anna Durbin, MD
role: Principal Investigator
affiliation: Johns Hopkins Bloomberg School of Public Health
facility: 
facility: 
country: United States
citation: Durbin AP, Wright PF, Cox A, Kagucia W, Elwood D, Henderson S, Wanionek K, Speicher J, Whitehead SS, Pletnev AG. The live attenuated chimeric vaccine rWN/DEN4Delta30 is well-tolerated and immunogenic in healthy flavivirus-naive adult volunteers. Vaccine. 2013 Nov 19;31(48):5772-7. doi: 10.1016/j.vaccine.2013.07.064. Epub 2013 Aug 19.
PMID: 23968769
responsible party type: Sponsor
mesh term: Encephalitis