<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/NCT02996448</url>
  </required_header>
  <id_info>
    <org_study_id>170017</org_study_id>
    <secondary_id>17-I-0017</secondary_id>
    <nct_id>NCT02996448</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, and Immunogenicity of One Dose of NDV 3A Vaccine in People With STAT3-Mutated Hyper-IgE Syndrome</brief_title>
  <official_title>A Phase 2a Study to Evaluate the Safety, Tolerability, and Immunogenicity of One Dose of NDV-3A Vaccine in Patients With STAT3-Mutated Hyper-IgE Syndrome</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 Institutes of Health Clinical Center (CC)</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
  </oversight_info>
  <brief_summary>
    <textblock>
      Background:&#xD;
&#xD;
      AD-HIES is a disease that weakens the immune system. It puts people at risk for infections,&#xD;
      particularly Staph and Candida infections. Researchers want to test a vaccine that may help&#xD;
      keep people from getting these infections, which would help people with AD-HIES.&#xD;
&#xD;
      Objective:&#xD;
&#xD;
      To test the new vaccine NDV-3A for protection against infection from the yeast Candida and&#xD;
      the bacterium Staphylococcus aureus (Staph).&#xD;
&#xD;
      Eligibility:&#xD;
&#xD;
      Adults ages 18-55 who have AD-HIES&#xD;
&#xD;
      Healthy volunteers ages 18-55&#xD;
&#xD;
      Design:&#xD;
&#xD;
      Participants will have 6-7 study visits over 6-7 months. They will also be contacted by phone&#xD;
      in between some visits.&#xD;
&#xD;
      Participants will be screened with a medical history, physical exam, and blood and urine&#xD;
      tests.&#xD;
&#xD;
      Participants will have 2 baseline visits. They will have repeat the screening tests. They&#xD;
      will have samples of saliva, stool, skin, mucus (oral, nasal, and/or vaginal) collected.&#xD;
      Vaginal and stool samples are optional. Any eczema on their skin will be looked at.&#xD;
&#xD;
      Participants will fill out symptom diary cards to record how they feel.&#xD;
&#xD;
      Participants will have the NDV-3A vaccine injected into a muscle in the arm.&#xD;
&#xD;
      Participants will return the next 2 days. They will have a physical exam. Blood will be&#xD;
      collected.&#xD;
&#xD;
      Participants will have 2 more follow-up visits at the NIH. They will have a physical exam.&#xD;
      They will have blood, saliva, stool, skin, vaginal fluid, and/or mucus samples collected.&#xD;
      Vaginal and stool samples are optional.&#xD;
&#xD;
      Participants will be called once a month for 5 months after the vaccination. There is an&#xD;
      optional visit about 6 weeks after the vaccination. Participants will provide a blood sample&#xD;
      at this visit.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Autosomal-dominant hyper-IgE syndrome (AD-HIES) is characterized by recurrent Staphylococcus&#xD;
      aureus and Candida epithelial infections, which is thought to be due, in part, to a lack of&#xD;
      Th17 cell differentiation, thus impairing epithelial immunity. Treatment of AD-HIES is&#xD;
      primarily supportive with prophylactic antibiotics; however, this is limited by microbial&#xD;
      resistance and intolerance of medications, and infections do still occur. Immunological&#xD;
      intervention with a vaccine could improve quality of life by preventing these infections&#xD;
      altogether.&#xD;
&#xD;
      The NDV-3A vaccine consists of a recombinant protein derived from the Candida Als3 adhesion&#xD;
      protein. This protein is homologous to surface proteins on S aureus and has been shown in&#xD;
      preclinical studies to protect against both intravascular and subcutaneous challenge with S&#xD;
      aureus. Therefore, NDV-3A represents not only the first antifungal vaccine, but also the&#xD;
      first vaccine to provide cross-kingdom protection. In Phase 1 and Phase 2 studies in healthy&#xD;
      volunteers (150 receiving vaccine), the safety profile of this vaccine is very reassuring as&#xD;
      the vaccine elicits a strong antibody response after a single dose in all vaccinees as well&#xD;
      as a Th1 and/or Th17 response in the majority of vaccinees. We will enroll 20 healthy adult&#xD;
      volunteers and 20 adults with AD-HIES in an open-label, single-dose study to assess the&#xD;
      immunological response to and the safety/tolerability of the NDV-3A vaccine. We anticipate an&#xD;
      increase in baseline anti-Als3 IgG within 2 weeks post-vaccination.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Safety concerns led to early termination.&#xD;
  </why_stopped>
  <start_date>November 17, 2016</start_date>
  <completion_date type="Actual">October 9, 2018</completion_date>
  <primary_completion_date type="Actual">July 22, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent of Each Group With at Least a Four-fold Increase in Anti rAls3 Antibody Titer.</measure>
    <time_frame>2 weeks after vaccination</time_frame>
    <description>Antibody titer</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Serious Adverse Events That Led to Study Termination.</measure>
    <time_frame>Up to 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anti-Als3 Antibody Titers at 6 Months After Vaccination in Patients With AD HIES and Healthy Volunteers.</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Autosomal-dominant Hyper-IgE Syndrome</condition>
  <arm_group>
    <arm_group_label>NDV 3A vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NDV-3A</intervention_name>
    <description>A vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection.</description>
    <arm_group_label>NDV 3A vaccine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        -  INCLUSION CRITERIA:&#xD;
&#xD;
               1. Age 18-55 years.&#xD;
&#xD;
               2. For healthy volunteers: in general good health, without significant medical&#xD;
                  illness, physical exam findings, or significant laboratory abnormalities as&#xD;
                  determined by the investigator.&#xD;
&#xD;
               3. For participants with AD-HIES: confirmation of diagnosis with a STAT3 mutation.&#xD;
&#xD;
               4. Participants who can get pregnant must be willing to use an acceptable form of&#xD;
                  contraception for the duration of participation and have a negative pregnancy&#xD;
                  test at screening.&#xD;
&#xD;
               5. Agree to allow storage of biological samples for future research.&#xD;
&#xD;
        EXCLUSION CRITERIA:&#xD;
&#xD;
          1. Has a history of allergic response or other serious reaction to aluminum and/or yeast&#xD;
             products.&#xD;
&#xD;
          2. Has a history of clinically significant allergy including anaphylaxis or other serious&#xD;
             reaction to food, vaccines, or other drugs, that in the opinion of the investigator,&#xD;
             might put the participant at undue risk.&#xD;
&#xD;
          3. Has an active infection (such as S aureus abscess, pneumonia, acute Candida&#xD;
             mucocutaneous infection). Baseline state of chronic infections will be considered by&#xD;
             the PI (eg, chronic Pseudomonas infection in lung).&#xD;
&#xD;
          4. Has an active infection with hepatitis B, hepatitis C, or HIV.&#xD;
&#xD;
          5. Has received or is planning to receive any investigational drug, investigational&#xD;
             vaccine, or investigational device within four weeks prior to vaccination, or at any&#xD;
             other time during their participation in the study.&#xD;
&#xD;
          6. Has received or is planning to receive any other live vaccine within three weeks&#xD;
             before vaccination or for three weeks after vaccination.&#xD;
&#xD;
          7. Self-reported current alcohol abuse or addiction.&#xD;
&#xD;
          8. Self-reported current illicit drug abuse or addiction, or drug screen positive for&#xD;
             illicit drugs.&#xD;
&#xD;
          9. Current or planned use, within 3 weeks before vaccination, of any medications or&#xD;
             treatments that may alter immune responses to the study vaccine (eg, immunosuppressive&#xD;
             medications including systemic corticosteroids, cyclosporine, tacrolimus, cytotoxic&#xD;
             drugs, Bacillus Calmette-Guerin, monoclonal antibodies, or radiation therapy).&#xD;
             Topical, intranasal, or inhaled immunosuppressants such as corticosteroids will be&#xD;
             allowed.&#xD;
&#xD;
         10. Current or planned use within 2 weeks before vaccination of immune globulin&#xD;
             replacement.&#xD;
&#xD;
         11. Has any of the following laboratory abnormalities at the screening visit:&#xD;
&#xD;
               1. Alanine transaminase (ALT), aspartate transaminase (AST), and/or alkaline&#xD;
&#xD;
                  phosphatase (ALP) &gt; 1.5 times the upper limit of normal (ULN).&#xD;
&#xD;
               2. Total bilirubin level &gt; 1.5 times the ULN&#xD;
&#xD;
               3. Serum creatinine level &gt; 1.5 times the ULN&#xD;
&#xD;
               4. Absolute neutrophil count &lt; 750 cells/microliter&#xD;
&#xD;
               5. Hemoglobin &lt; 9 mg/dL&#xD;
&#xD;
               6. Platelet count &lt; 100,000&#xD;
&#xD;
         12. Refusal or inability to comply with study procedures to the extent that it is&#xD;
             potentially harmful to the participant or to the integrity of the study data.&#xD;
&#xD;
         13. Has donated blood/plasma within four weeks before vaccination.&#xD;
&#xD;
         14. Is pregnant or breastfeeding, or intends to become pregnant over the course of the&#xD;
             study.&#xD;
&#xD;
         15. Is unable to commit to the follow-up visits and or has unreliable access to a&#xD;
             telephone for follow-up contacts, either by self-admission (self-reporting) or in the&#xD;
             opinion of the investigator.&#xD;
&#xD;
         16. Any other condition the investigator believes would interfere with the participant s&#xD;
             ability to provide informed consent, comply with study instructions, or that might&#xD;
             confound the interpretation of the study results or put the participant at undue risk.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alexandra Freeman, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Institute of Allergy and Infectious Diseases (NIAID)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Institutes of Health Clinical Center</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20892</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-I-0017.html</url>
    <description>NIH Clinical Center Detailed Web Page</description>
  </link>
  <reference>
    <citation>Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012 Feb;1250:25-32. doi: 10.1111/j.1749-6632.2011.06387.x. Epub 2012 Jan 23.</citation>
    <PMID>22268731</PMID>
  </reference>
  <reference>
    <citation>Spellberg BJ, Ibrahim AS, Avanesian V, Fu Y, Myers C, Phan QT, Filler SG, Yeaman MR, Edwards JE Jr. Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J Infect Dis. 2006 Jul 15;194(2):256-60. doi: 10.1086/504691. Epub 2006 Jun 6.</citation>
    <PMID>16779733</PMID>
  </reference>
  <reference>
    <citation>Liu Y, Filler SG. Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot Cell. 2011 Feb;10(2):168-73. doi: 10.1128/EC.00279-10. Epub 2010 Nov 29.</citation>
    <PMID>21115738</PMID>
  </reference>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>December 16, 2016</study_first_submitted>
  <study_first_submitted_qc>December 16, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 19, 2016</study_first_posted>
  <results_first_submitted>June 22, 2020</results_first_submitted>
  <results_first_submitted_qc>June 22, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">June 30, 2020</results_first_posted>
  <last_update_submitted>June 22, 2020</last_update_submitted>
  <last_update_submitted_qc>June 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AD-HIES</keyword>
  <keyword>Anti-rAls3 Antibody</keyword>
  <keyword>Staphylococcus Aureus</keyword>
  <keyword>Candida Albicans</keyword>
  <keyword>RNA Transcriptome</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Job Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 13, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/48/NCT02996448/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Healthy volunteers were not enrolled to the study due to the early termination. The three subjects enrolled were those with AD-HIES.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Vaccination Group, Single Arm Study</title>
          <description>Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection.&#xD;
NDV-3A: A vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Study terminated due to adverse effects</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Vaccination Group- Single Arm Study</title>
          <description>Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection.&#xD;
NDV-3A: A vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20" lower_limit="19" upper_limit="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent of Each Group With at Least a Four-fold Increase in Anti rAls3 Antibody Titer.</title>
        <description>Antibody titer</description>
        <time_frame>2 weeks after vaccination</time_frame>
        <population>As study was stopped prematurely due to safety concerns, the data was not obtained.</population>
        <group_list>
          <group group_id="O1">
            <title>Vaccine Recipients</title>
            <description>Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection.&#xD;
NDV-3A: A vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent of Each Group With at Least a Four-fold Increase in Anti rAls3 Antibody Titer.</title>
          <description>Antibody titer</description>
          <population>As study was stopped prematurely due to safety concerns, the data was not obtained.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Serious Adverse Events That Led to Study Termination.</title>
        <time_frame>Up to 6 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vaccination Group- Single Arm Study</title>
            <description>Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection.&#xD;
NDV-3A: A vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Serious Adverse Events That Led to Study Termination.</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Anti-Als3 Antibody Titers at 6 Months After Vaccination in Patients With AD HIES and Healthy Volunteers.</title>
        <time_frame>6 months</time_frame>
        <population>Data were not collected due to premature termination of study.</population>
        <group_list>
          <group group_id="O1">
            <title>Vaccination Group- Single Arm Study</title>
            <description>Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection.&#xD;
NDV-3A: A vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection.</description>
          </group>
        </group_list>
        <measure>
          <title>Anti-Als3 Antibody Titers at 6 Months After Vaccination in Patients With AD HIES and Healthy Volunteers.</title>
          <population>Data were not collected due to premature termination of study.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 6 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Vaccination Group- Single Arm Study</title>
          <description>Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection.&#xD;
NDV-3A: A vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylaxis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Injection site pain</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Eczema exacerbation</sub_title>
                <assessment>Systematic Assessment</assessment>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Alexandra Freeman</name_or_title>
      <organization>NIAID, NIH</organization>
      <phone>301-594-9045</phone>
      <email>freemaal@mail.nih.gov</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02996448
org study id: 170017
secondary id: 17-I-0017
nct id: NCT02996448
lead sponsor: 
is fda regulated drug: Yes
Background:

      AD-HIES is a disease that weakens the immune system. It puts people at risk for infections,
      particularly Staph and Candida infections. Researchers want to test a vaccine that may help
      keep people from getting these infections, which would help people with AD-HIES.

      Objective:

      To test the new vaccine NDV-3A for protection against infection from the yeast Candida and
      the bacterium Staphylococcus aureus (Staph).

      Eligibility:

      Adults ages 18-55 who have AD-HIES

      Healthy volunteers ages 18-55

      Design:

      Participants will have 6-7 study visits over 6-7 months. They will also be contacted by phone
      in between some visits.

      Participants will be screened with a medical history, physical exam, and blood and urine
      tests.

      Participants will have 2 baseline visits. They will have repeat the screening tests. They
      will have samples of saliva, stool, skin, mucus (oral, nasal, and/or vaginal) collected.
      Vaginal and stool samples are optional. Any eczema on their skin will be looked at.

      Participants will fill out symptom diary cards to record how they feel.

      Participants will have the NDV-3A vaccine injected into a muscle in the arm.

      Participants will return the next 2 days. They will have a physical exam. Blood will be
      collected.

      Participants will have 2 more follow-up visits at the NIH. They will have a physical exam.
      They will have blood, saliva, stool, skin, vaginal fluid, and/or mucus samples collected.
      Vaginal and stool samples are optional.

      Participants will be called once a month for 5 months after the vaccination. There is an
      optional visit about 6 weeks after the vaccination. Participants will provide a blood sample
      at this visit.
Autosomal-dominant hyper-IgE syndrome (AD-HIES) is characterized by recurrent Staphylococcus
      aureus and Candida epithelial infections, which is thought to be due, in part, to a lack of
      Th17 cell differentiation, thus impairing epithelial immunity. Treatment of AD-HIES is
      primarily supportive with prophylactic antibiotics; however, this is limited by microbial
      resistance and intolerance of medications, and infections do still occur. Immunological
      intervention with a vaccine could improve quality of life by preventing these infections
      altogether.

      The NDV-3A vaccine consists of a recombinant protein derived from the Candida Als3 adhesion
      protein. This protein is homologous to surface proteins on S aureus and has been shown in
      preclinical studies to protect against both intravascular and subcutaneous challenge with S
      aureus. Therefore, NDV-3A represents not only the first antifungal vaccine, but also the
      first vaccine to provide cross-kingdom protection. In Phase 1 and Phase 2 studies in healthy
      volunteers (150 receiving vaccine), the safety profile of this vaccine is very reassuring as
      the vaccine elicits a strong antibody response after a single dose in all vaccinees as well
      as a Th1 and/or Th17 response in the majority of vaccinees. We will enroll 20 healthy adult
      volunteers and 20 adults with AD-HIES in an open-label, single-dose study to assess the
      immunological response to and the safety/tolerability of the NDV-3A vaccine. We anticipate an
      increase in baseline anti-Als3 IgG within 2 weeks post-vaccination.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Percent of Each Group With at Least a Four-fold Increase in Anti rAls3 Antibody Titer.
time frame: 2 weeks after vaccination
description: Antibody titer
measure: Number of Participants With Serious Adverse Events That Led to Study Termination.
time frame: Up to 6 months
measure: Anti-Als3 Antibody Titers at 6 Months After Vaccination in Patients With AD HIES and Healthy Volunteers.
time frame: 6 months
arm group label: NDV 3A vaccine
arm group type: Experimental
description: Participants will receive a single dose of 0.5 mL (300 micrograms of rAls3) administered via IM injection.
intervention type: Drug
intervention name: NDV-3A
description: A vaccine containing recombinant Candida albicans agglutinin-like sequence 3 (rAls3) protein as the antigen, formulated with AlOH adjuvant in phosphate buffered saline. Participants will receive a single 0.5 mL dose containing 300 micrograms of rAls3 and 0.5 mg of aluminum as AlOH, delivered via intramuscular injection.
arm group label: NDV 3A vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Alexandra Freeman, M.D.
role: Principal Investigator
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
facility: 
country: United States
url: https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2017-I-0017.html
description: NIH Clinical Center Detailed Web Page
citation: Sowerwine KJ, Holland SM, Freeman AF. Hyper-IgE syndrome update. Ann N Y Acad Sci. 2012 Feb;1250:25-32. doi: 10.1111/j.1749-6632.2011.06387.x. Epub 2012 Jan 23.
PMID: 22268731
citation: Spellberg BJ, Ibrahim AS, Avanesian V, Fu Y, Myers C, Phan QT, Filler SG, Yeaman MR, Edwards JE Jr. Efficacy of the anti-Candida rAls3p-N or rAls1p-N vaccines against disseminated and mucosal candidiasis. J Infect Dis. 2006 Jul 15;194(2):256-60. doi: 10.1086/504691. Epub 2006 Jun 6.
PMID: 16779733
citation: Liu Y, Filler SG. Candida albicans Als3, a multifunctional adhesin and invasin. Eukaryot Cell. 2011 Feb;10(2):168-73. doi: 10.1128/EC.00279-10. Epub 2010 Nov 29.
PMID: 21115738
responsible party type: Sponsor
mesh term: Job Syndrome
mesh term: Syndrome
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 