<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/NCT03806686</url>
  </required_header>
  <id_info>
    <org_study_id>CT-QTP101-001</org_study_id>
    <nct_id>NCT03806686</nct_id>
  </id_info>
  <brief_title>Phase 2a Clinical Trial of ID93+GLA-SE Vaccine in BCG-vaccinated Healthy Healthcare Workers</brief_title>
  <official_title>A Phase 2a, Randomized, Double-blind, Placebo-Controlled Study to Evaluate the Safety and Explore the Immunogenicity and Efficacy of ID93+GLA-SE Vaccine in BCG-Vaccinated Healthy Healthcare Workers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Quratis Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Access to Advanced Health Institute (AAHI)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Quratis Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the experimental tuberculosis (TB) vaccine called&#xD;
      ID93+GLA-SE. The safety, immunogenicity, and efficacy of ID93+GLA-SE will be compared to&#xD;
      placebo, after three intramuscular (IM) injections one month apart in healthy healthcare&#xD;
      workers. The healthcare workers will all have had the childhood TB vaccine called BCG, and&#xD;
      all of them must have a negative result for a blood test for exposure to the bacteria that&#xD;
      cause TB (QuantiFERON-TB Gold Plus, or &quot;QFT&quot;). Study participants will be followed for 12&#xD;
      months after the last injection for safety reasons. Blood will be drawn for laboratory tests&#xD;
      for safety, immunogenicity, and efficacy tests. Efficacy will be evaluated by further QFT&#xD;
      testing. The study hypothesis is that the vaccine is safe, immunogenic, and effective in this&#xD;
      study population.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      After signing a written informed consent to participate in the study, subjects will be&#xD;
      screened by required assessments per protocol. Eligible subjects who meet the&#xD;
      inclusion/exclusion criteria will be randomized in a 1:1:1 ratio to Group 1, Group 2, or&#xD;
      Control Group, receiving either ID93+GLA-SE or saline placebo on Days 0, 28, and 56. The&#xD;
      investigator will evaluate the safety, immunogenicity, and efficacy of the Investigational&#xD;
      Product in the subjects throughout the study.&#xD;
&#xD;
      For safety assessment, subjects will be instructed to record any adverse events in the&#xD;
      subject diary after each vaccination. Subject's safety will be reported to the investigators&#xD;
      after 7 days from each vaccination (Days 7, 35, 63) via site visit or a phone call. Solicited&#xD;
      AEs will be collected up to 7 days after the final vaccination with the Investigational&#xD;
      Product and un-solicited AEs will be collected up to 28 days after the final vaccination with&#xD;
      the Investigational Product. For long-term safety assessment of the Investigational Product,&#xD;
      serious adverse events and adverse events of special interest will be monitored up to 12&#xD;
      months after the final vaccination with the Investigational Product.&#xD;
&#xD;
      For immunogenicity assessment, blood samples for immunology assays will be collected and&#xD;
      analyzed before and after each vaccination. For efficacy assessment, QFT-Gold Plus testing&#xD;
      will be performed after 3 months and 14months from the first vaccination with the&#xD;
      Investigational Product.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">May 31, 2018</start_date>
  <completion_date type="Anticipated">June 2020</completion_date>
  <primary_completion_date type="Anticipated">March 2020</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>Participants will be assigned to one of three groups: Low dose ID93+GLA-SE, High dose ID93+GLA-SE, or Control Group.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>Since the vials of ID93+GLA-SE and placebo control (normal saline) and their appearances after preparation are different, for double-blinding of the study, the study nurse who administers the study drug or the study pharmacist who stores and manages the study drug will be unblinded to maintain the quality of study blinding. Additionally, an unblinded study monitor will be responsible for confirming the quantity and release of the study drugs. Unblinded study personnels and unblinded study monitor should only be involved in the duties related to administration and/or recording of the study drug, and must not be involved in other duties that may break double-blinding of the study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse events</measure>
    <time_frame>Solicited AEs for 7 days following each injection, unsolicited AEs for 28 days after each injection, SAEs and AESIs for 12 months after the last injection.</time_frame>
    <description>Solicited (local and systemic reactogenicity), unsolicited (all other adverse events, including laboratory assessments and vital signs), serious AEs and AEs of special interest.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Humoral and cellular immunogenicity assays</measure>
    <time_frame>Days 0, 28, 56, 84, and 12 months after last injection.</time_frame>
    <description>Immunogenicity will be evaluated by measuring humoral and cellular responses to ID93 + GLA-SE at specified timepoints</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy at prevention of latent Mtb infection (QFT conversion)</measure>
    <time_frame>3 months and 14 months after the first injection.</time_frame>
    <description>Positive response rate for latent tuberculosis infection from QuantiFERON®-TB Gold Plus assay.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">107</enrollment>
  <condition>Tuberculosis</condition>
  <arm_group>
    <arm_group_label>Low dose ID93+GLA-SE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 0.5 mL (2 μg ID93 + 5 μg GLA-SE) intramuscular injection (IM) into deltoid area, three times in 4-week intervals on Days 0, 28, and 56.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>High dose ID93+GLA-SE</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 0.5 mL (10 μg ID93 + 5 μg GLA-SE) IM injection into deltoid area, three times in 4-week intervals on Days 0, 28, and 56.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive 0.5 mL Placebo (physiological saline) IM injection into deltoid area, three times on 4-week intervals on Days 0, 28, and 56.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Sterile normal saline</description>
    <arm_group_label>Control group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ID93+GLA-SE</intervention_name>
    <description>ID93 is a recombinant protein antigen comprising 4 antigens from Mycobacterium tuberculosis (Mtb). The adjuvant GLA-SE is a TLR4 agonist in a stable oil-in-water emulsion.</description>
    <arm_group_label>High dose ID93+GLA-SE</arm_group_label>
    <arm_group_label>Low dose ID93+GLA-SE</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female who is ≥19 and &lt;65 years of age.&#xD;
&#xD;
          2. Healthcare workers who are QuantiFERON®-TB Gold Plus negative (not latently infected&#xD;
             with Mtb) at screening.&#xD;
&#xD;
          3. Able to comply with the scheduled visits, and are expected to continue working in the&#xD;
             current medical institution and be available for a continuous follow-up by the&#xD;
             investigator via provided contact information.&#xD;
&#xD;
          4. Only for female subjects of childbearing potential:&#xD;
&#xD;
               -  Must be HCG-negative from serum or urine pregnancy test, at screening;&#xD;
&#xD;
                    -  Agreed to use one of the following acceptable birth control methods to avoid&#xD;
                       pregnancy until the end of study (Visit 9): hormonal contraceptives,&#xD;
                       intrauterine device (IUD) or intrauterine system (IUS), tubal ligation, or&#xD;
                       combination of barrier methods (combined use of barrier methods such as male&#xD;
                       condoms, female condoms, cervical cap, diaphragm, sponge, or implant).&#xD;
&#xD;
          5. History of BCG vaccination that is confirmed through medical examination (i.e., asking&#xD;
             a subject about his/her condition) or presence of a scar.&#xD;
&#xD;
          6. Body mass index (BMI) ≥19 and ≤33 (kg/m^2) at screening&#xD;
&#xD;
          7. Subjects who understand the study procedures, and voluntarily decide to participate in&#xD;
             the study and sign the informed consent form..&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of positive tuberculin skin test or positive QuantiFERON®-TB results.&#xD;
&#xD;
          2. History of severe chronic disease that may compromise the safety of the subject during&#xD;
             the study (e.g., impairment of pulmonary function from tuberculosis infection or other&#xD;
             pulmonary disease; chronic illness with signs of cardiac or renal failure; suspected&#xD;
             progressive neurological disease or uncontrolled epilepsy).&#xD;
&#xD;
          3. Body temperature ≥ 38℃ at the time of randomization or within 24 hours before&#xD;
             randomization, from acute fever, acute respiratory diseases, or active infection.&#xD;
&#xD;
          4. Malignant tumors or a history of malignant tumors.&#xD;
&#xD;
          5. Plans to have surgery during the study period.&#xD;
&#xD;
          6. Impaired immune functions including autoimmune disease or immunodeficiency disease.&#xD;
&#xD;
          7. History of Guillain-Barre syndrome.&#xD;
&#xD;
          8. Subjects with a history of anaphylaxis or severe allergic reaction to vaccines, eggs,&#xD;
             or other allergens.&#xD;
&#xD;
          9. Subjects living with a household member who has active TB or infectious TB.&#xD;
&#xD;
         10. Clinically significant abnormal laboratory values for any of the following tests&#xD;
             conducted in the study center, prior to randomization:&#xD;
&#xD;
               -  Hemoglobin, hematocrit, absolute neutrophil count, absolute lymphocyte count, or&#xD;
                  platelet count: &lt; LLN (lower limit of normal)&#xD;
&#xD;
               -  White blood cell count: &gt;ULN (upper limit of normal) or &lt;LLN (lower limit of&#xD;
                  normal) (i.e., must be within normal limits)&#xD;
&#xD;
               -  ALT, AST, total bilirubin, alkaline phosphatase, creatinine, or blood urea&#xD;
                  nitrogen (BUN): &gt;ULN (upper limit of normal)&#xD;
&#xD;
         11. Received an immunosuppressant, immunity-modifying drug, or other treatment that may&#xD;
             affect the immune system including cytotoxic anti-cancer agents or radiotherapy,&#xD;
             within 3 months before the randomization.&#xD;
&#xD;
         12. Use of systemic steroids (equivalent to daily prednisone ≥ 15mg/day for more than 14&#xD;
             days), inhaled or intranasal steroids, within 3 months before randomization; however,&#xD;
             use of topical corticosteroids are acceptable, regardless of dose.&#xD;
&#xD;
         13. Use of immunoglobulin or blood products within 3 months before randomization or plans&#xD;
             to use them during the study period.&#xD;
&#xD;
         14. Human Immunodeficiency Virus (HIV) positive at screening.&#xD;
&#xD;
         15. Subjects with chronic hepatitis (e.g., hepatitis B core antibody or hepatitis C&#xD;
             antibody positive) at screening.&#xD;
&#xD;
         16. Unable to discontinue current chronic drug therapy such as thyroxin, insulin, or other&#xD;
             medications with hepatotoxicity or myelotoxicity; however, estrogen and progesterone&#xD;
             replacement therapy or contraceptives, and topical medications are acceptable.&#xD;
&#xD;
         17. Pregnant or lactating.&#xD;
&#xD;
         18. Received other vaccines within 4 weeks before screening or plans to receive them from&#xD;
             the day of screening to 4 weeks after the last vaccination with the Investigational&#xD;
             Product or within 4 weeks before the End Visit.&#xD;
&#xD;
         19. Received other investigational drugs within 4 weeks before screening.&#xD;
&#xD;
         20. Subjects deemed ineligible by investigator based on other reasons.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yu Hwa Choi</last_name>
    <role>Study Director</role>
    <affiliation>Quratis Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ajou University Hospital</name>
      <address>
        <city>Gyeonggi-do</city>
        <zip>16499</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chung-Ang University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>06973</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 14, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 16, 2019</study_first_posted>
  <last_update_submitted>May 29, 2019</last_update_submitted>
  <last_update_submitted_qc>May 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 31, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Tuberculosis, TB, vaccine, adjuvant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03806686
org study id: CT-QTP101-001
nct id: NCT03806686
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The purpose of this study is to evaluate the experimental tuberculosis (TB) vaccine called
      ID93+GLA-SE. The safety, immunogenicity, and efficacy of ID93+GLA-SE will be compared to
      placebo, after three intramuscular (IM) injections one month apart in healthy healthcare
      workers. The healthcare workers will all have had the childhood TB vaccine called BCG, and
      all of them must have a negative result for a blood test for exposure to the bacteria that
      cause TB (QuantiFERON-TB Gold Plus, or "QFT"). Study participants will be followed for 12
      months after the last injection for safety reasons. Blood will be drawn for laboratory tests
      for safety, immunogenicity, and efficacy tests. Efficacy will be evaluated by further QFT
      testing. The study hypothesis is that the vaccine is safe, immunogenic, and effective in this
      study population.
After signing a written informed consent to participate in the study, subjects will be
      screened by required assessments per protocol. Eligible subjects who meet the
      inclusion/exclusion criteria will be randomized in a 1:1:1 ratio to Group 1, Group 2, or
      Control Group, receiving either ID93+GLA-SE or saline placebo on Days 0, 28, and 56. The
      investigator will evaluate the safety, immunogenicity, and efficacy of the Investigational
      Product in the subjects throughout the study.

      For safety assessment, subjects will be instructed to record any adverse events in the
      subject diary after each vaccination. Subject's safety will be reported to the investigators
      after 7 days from each vaccination (Days 7, 35, 63) via site visit or a phone call. Solicited
      AEs will be collected up to 7 days after the final vaccination with the Investigational
      Product and un-solicited AEs will be collected up to 28 days after the final vaccination with
      the Investigational Product. For long-term safety assessment of the Investigational Product,
      serious adverse events and adverse events of special interest will be monitored up to 12
      months after the final vaccination with the Investigational Product.

      For immunogenicity assessment, blood samples for immunology assays will be collected and
      analyzed before and after each vaccination. For efficacy assessment, QFT-Gold Plus testing
      will be performed after 3 months and 14months from the first vaccination with the
      Investigational Product.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Participants will be assigned to one of three groups: Low dose ID93+GLA-SE, High dose ID93+GLA-SE, or Control Group.
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: Since the vials of ID93+GLA-SE and placebo control (normal saline) and their appearances after preparation are different, for double-blinding of the study, the study nurse who administers the study drug or the study pharmacist who stores and manages the study drug will be unblinded to maintain the quality of study blinding. Additionally, an unblinded study monitor will be responsible for confirming the quantity and release of the study drugs. Unblinded study personnels and unblinded study monitor should only be involved in the duties related to administration and/or recording of the study drug, and must not be involved in other duties that may break double-blinding of the study.
measure: Adverse events
time frame: Solicited AEs for 7 days following each injection, unsolicited AEs for 28 days after each injection, SAEs and AESIs for 12 months after the last injection.
description: Solicited (local and systemic reactogenicity), unsolicited (all other adverse events, including laboratory assessments and vital signs), serious AEs and AEs of special interest.
measure: Humoral and cellular immunogenicity assays
time frame: Days 0, 28, 56, 84, and 12 months after last injection.
description: Immunogenicity will be evaluated by measuring humoral and cellular responses to ID93 + GLA-SE at specified timepoints
measure: Efficacy at prevention of latent Mtb infection (QFT conversion)
time frame: 3 months and 14 months after the first injection.
description: Positive response rate for latent tuberculosis infection from QuantiFERON®-TB Gold Plus assay.
arm group label: Low dose ID93+GLA-SE
arm group type: Experimental
description: Participants will receive 0.5 mL (2 μg ID93 + 5 μg GLA-SE) intramuscular injection (IM) into deltoid area, three times in 4-week intervals on Days 0, 28, and 56.
arm group label: High dose ID93+GLA-SE
arm group type: Experimental
description: Participants will receive 0.5 mL (10 μg ID93 + 5 μg GLA-SE) IM injection into deltoid area, three times in 4-week intervals on Days 0, 28, and 56.
arm group label: Control group
arm group type: Placebo Comparator
description: Participants will receive 0.5 mL Placebo (physiological saline) IM injection into deltoid area, three times on 4-week intervals on Days 0, 28, and 56.
intervention type: Biological
intervention name: Placebo
description: Sterile normal saline
arm group label: Control group
intervention type: Biological
intervention name: ID93+GLA-SE
description: ID93 is a recombinant protein antigen comprising 4 antigens from Mycobacterium tuberculosis (Mtb). The adjuvant GLA-SE is a TLR4 agonist in a stable oil-in-water emulsion.
arm group label: High dose ID93+GLA-SE
arm group label: Low dose ID93+GLA-SE
criteria: 
gender: All
minimum age: 19 Years
maximum age: 64 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Yu Hwa Choi
role: Study Director
affiliation: Quratis Inc.
facility: 
facility: 
facility: 
country: Korea, Republic of
responsible party type: Sponsor
mesh term: Tuberculosis
sharing ipd: No