<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/NCT04498325</url>
  </required_header>
  <id_info>
    <org_study_id>202009065</org_study_id>
    <nct_id>NCT04498325</nct_id>
  </id_info>
  <brief_title>Evaluating the Effect of NT-I7, a Long Acting Interleukin-7, to Increase Lymphocyte Counts and Enhance Immune Clearance of SARS-CoV-2 (COVID-19)</brief_title>
  <official_title>A Phase I and Pilot Study Evaluating the Effect of NT-I7, a Long Acting Interleukin-7, to Increase Lymphocyte Counts and Enhance Immune Clearance of SARS-CoV-2</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NeoImmune Tech</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Lymphopenia is common in patients with COVID-19 and is associated with worse clinical&#xD;
      outcomes. NT-I7 is a long-acting human interleukin-7 (IL-7) that has been shown to increase&#xD;
      absolute lymphocyte count (ALC) and CD4+ and CD8+ T cell counts with a well-tolerated safety&#xD;
      profile in humans. In this study, patients who have tested positive for SARS-CoV-2 by PCR&#xD;
      testing without severe disease and with ALC &lt;1500 cells/mm3 will be enrolled.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Principal investigator is leaving the institution.&#xD;
  </why_stopped>
  <start_date type="Anticipated">July 31, 2021</start_date>
  <completion_date type="Anticipated">April 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">April 30, 2022</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>
    <intervention_model_description>The study will open as a phase I study to test three different dose levels of NT-I7. Once a safe tolerated dose is established, the pilot portion of the study will be activated wherein participants will be randomized on a 1:1 basis to receive a single injection of NT-I7 (at the safe tolerated dose) or placebo.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
    <masking_description>The clinicians, participants, and clinical research coordinators will be blinded</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Safe and tolerable dose of NT-I7 (Phase I only)</measure>
    <time_frame>Completion of DLT assessment window of Phase I portion of study (estimated to be 8 months)</time_frame>
    <description>The safe tolerated dose is defined as the dose level immediately below the dose level at which 1 patient of a cohort of 3 patients experiences dose-limiting toxicity within 14 days after administration of NT-I7&#xD;
Dose limiting toxicities (DLT) are defined as:&#xD;
A serious adverse event that is at least possibly related to NT-I7&#xD;
A grade 3 or higher adverse event that is at least possibly related to NT-I7 (excluding injection site swelling, irritation or discomfort)&#xD;
A clinically significant lab abnormality that is at least possibly related to NT-I7</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent change in absolute lymphocyte count (ALC)</measure>
    <time_frame>From baseline to Day 14</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent change in absolute lymphocyte count (ALC)</measure>
    <time_frame>From baseline through Day 21</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SARS-CoV-2 viral load</measure>
    <time_frame>From baseline to Day 7</time_frame>
    <description>-Using PCR from nasopharyngeal swab, oropharyngeal swab or saliva</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in SARS-CoV-2 viral load</measure>
    <time_frame>From baseline to Day 14</time_frame>
    <description>-Using PCR from nasopharyngeal swab, oropharyngeal swab or saliva</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>COVID-19 Symptom severity as measured by WHO Ordinal Scale for clinical improvement</measure>
    <time_frame>From baseline, day 7, day 14, and day 21</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to resolution of COVID-19 symptoms</measure>
    <time_frame>From baseline through Day 21</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of treatment-emergent adverse events</measure>
    <time_frame>From baseline through Day 21</time_frame>
    <description>-A treatment emergent adverse event (TEAE) is defined as any event that begins or worsens on or after date of first dose of study treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants by PCR result status (positive or negative)</measure>
    <time_frame>-From baseline to Day 7</time_frame>
    <description>-If quantitative PCR is not available</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants by PCR result status (positive or negative)</measure>
    <time_frame>From baseline to Day 14</time_frame>
    <description>-If quantitative PCR is not available</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>COVID-19</condition>
  <condition>SARS-CoV-2</condition>
  <arm_group>
    <arm_group_label>NT-I7 (Phase I)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In the phase I study, 3 dose levels of NT-I7 are planned. Dosing will be staggered such that there will be a minimum of 72 hours between the dosing of one participant and the dosing of the next participant&#xD;
NT-I7 will be given by intramuscular injection on Day 0&#xD;
Participants will also be given standard of care treatment for COVID-19</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NT-I7 (Pilot)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NT-I7 (dose determined by Phase I portion of study) will be given by intramuscular injection on Day 0&#xD;
Participants will also be given standard of care treatment for COVID-19</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo (Pilot)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo will be given by intramuscular injection on Day 0&#xD;
Participants will also be given standard of care treatment for COVID-19</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NT-I7</intervention_name>
    <description>Supplied by study</description>
    <arm_group_label>NT-I7 (Phase I)</arm_group_label>
    <arm_group_label>NT-I7 (Pilot)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Supplied by study</description>
    <arm_group_label>Placebo (Pilot)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood for research purposes</intervention_name>
    <description>Prior to injection (Day 0), Day 7, and Day 14</description>
    <arm_group_label>NT-I7 (Phase I)</arm_group_label>
    <arm_group_label>NT-I7 (Pilot)</arm_group_label>
    <arm_group_label>Placebo (Pilot)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood for pharmacokinetic samples</intervention_name>
    <description>-Phase I only: 1-2 hours prior to dosing, 6 hours after dosing, 24 hours after dosing, Day 7, Day 14, and Day 21</description>
    <arm_group_label>NT-I7 (Phase I)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Nasopharyngeal, oropharyngeal, or saliva swab</intervention_name>
    <description>-Prior to study treatment, Day 4(optional), Day 7, and Day 14</description>
    <arm_group_label>NT-I7 (Phase I)</arm_group_label>
    <arm_group_label>NT-I7 (Pilot)</arm_group_label>
    <arm_group_label>Placebo (Pilot)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood for anti-drug antibody (ADA)</intervention_name>
    <description>Baseline, Day 7, Day 14, Day 21, Day 60, and Day 90. Participants with ADA positivity on Day 90 will be monitored every 90 days until antibody level returns to baseline</description>
    <arm_group_label>NT-I7 (Phase I)</arm_group_label>
    <arm_group_label>NT-I7 (Pilot)</arm_group_label>
    <arm_group_label>Placebo (Pilot)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Tested PCR positive for SARS-CoV-2by nasopharyngeal swab, oropharyngeal swab, or&#xD;
             saliva.&#xD;
&#xD;
          -  Mild COVID-19, defined as WHO Ordinal Scale &lt;4 .&#xD;
&#xD;
          -  Respiratory rate &lt; 20 bpm, HR &lt; 90 bpm, and SpO2 &gt; 93% on room air at sea level.&#xD;
&#xD;
          -  Absolute lymphocyte count (ALC) &lt; 1500 cells/mm3 at the time of screening.&#xD;
&#xD;
          -  AST/ALT ≤ 3.0 x ULN, total bilirubin ≤ 1.5 x ULN (except if due to Gilbert's&#xD;
             syndrome).&#xD;
&#xD;
             -≥ 18 years of age.&#xD;
&#xD;
          -  First day of treatment must be no more than 10 days from onset of COVID-19 symptoms.&#xD;
&#xD;
          -  Must be willing to be closely monitored in the hospital or in an alternate setting&#xD;
             (e.g. clinical trial unit) for at least the first 7 days (±2 days allowed) following&#xD;
             NT-I7/placebo injection.&#xD;
&#xD;
          -  Individuals of reproductive potential must agree to either abstinence or use of at&#xD;
             least one study-approved form of contraception when engaging in sexual activities that&#xD;
             can result in pregnancy from the time of screening through 60 days for female and 120&#xD;
             days for male after study agent administration. Acceptable forms of contraception for&#xD;
             this study are male or female condoms, diaphragms or cervical caps with a spermicide,&#xD;
             or non-hormonal intrauterine devices.&#xD;
&#xD;
          -  Patients with factors or concomitant illness associated with higher risk of mortality&#xD;
             due to COVID-19 (such as older age, hypertension, diabetes, and/or COPD) are eligible.&#xD;
&#xD;
          -  Able to understand and willing to sign an IRB approved written informed consent&#xD;
             document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Receiving any other investigational agents which may affect patient's lymphocyte&#xD;
             counts. Note: There is no evidence that chloroquine or hydroxychloroquine could affect&#xD;
             lymphocyte counts. Thus, chloroquine or hydroxychloroquine use is not an exclusion&#xD;
             criteria for this study. Additionally, it is permissible for potential participants to&#xD;
             have received investigational or off-label agents for COVID-19 prior to or during&#xD;
             study participation.&#xD;
&#xD;
          -  Pregnant or breastfeeding women are excluded from this study because NT-I7 has not&#xD;
             been evaluated regarding its potential for teratogenic or abortifacients effects.&#xD;
             There is a potential risk for adverse events in nursing infants secondary to treatment&#xD;
             of the mother with the study drug; therefore, breastfeeding should be discontinued if&#xD;
             the mother is treated with NT-I7.&#xD;
&#xD;
          -  Transferred from ICU to the floor.&#xD;
&#xD;
          -  Requiring dialysis.&#xD;
&#xD;
          -  Shortness of breath or known hypoxia (defined as PaO2/FiO2 ≤ 300 mmHg), or signs of&#xD;
             serious lower airway disease.&#xD;
&#xD;
          -  Evidence of ARDS, SIRS/shock, or cardiac failure.&#xD;
&#xD;
          -  Elevated inflammatory markers such as CRP &gt; 2 x ULN, LDH &gt; 2 x ULN, D-dimer &gt; 2 x ULN,&#xD;
             ferritin &gt; ULN, or IL-6 &gt; ULN (when available).&#xD;
&#xD;
          -  Any established diagnosis of autoimmune disease requiring systemic treatment EXCEPT&#xD;
             for vitiligo or endocrine disease (such as diabetes, thyroid disease, and adrenal&#xD;
             disease) controlled by replacement therapy.&#xD;
&#xD;
          -  Receipt of live attenuated vaccine within 30 days before the study treatment. Examples&#xD;
             of live vaccines include, but are not limited to, the following: measles, mumps,&#xD;
             rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), Zoster,&#xD;
             and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed&#xD;
             virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist)&#xD;
             are live attenuated vaccines and are not allowed.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jian Campian, M.D., Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <removed_countries>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>http://www.siteman.wustl.edu</url>
    <description>Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine</description>
  </link>
  <verification_date>July 2021</verification_date>
  <study_first_submitted>July 30, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 4, 2020</study_first_posted>
  <last_update_submitted>July 29, 2021</last_update_submitted>
  <last_update_submitted_qc>July 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 5, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>SARS-CoV-2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
  </intervention_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/NCT04498325
org study id: 202009065
nct id: NCT04498325
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Lymphopenia is common in patients with COVID-19 and is associated with worse clinical
      outcomes. NT-I7 is a long-acting human interleukin-7 (IL-7) that has been shown to increase
      absolute lymphocyte count (ALC) and CD4+ and CD8+ T cell counts with a well-tolerated safety
      profile in humans. In this study, patients who have tested positive for SARS-CoV-2 by PCR
      testing without severe disease and with ALC <1500 cells/mm3 will be enrolled.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: The study will open as a phase I study to test three different dose levels of NT-I7. Once a safe tolerated dose is established, the pilot portion of the study will be activated wherein participants will be randomized on a 1:1 basis to receive a single injection of NT-I7 (at the safe tolerated dose) or placebo.
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
masking description: The clinicians, participants, and clinical research coordinators will be blinded
measure: Safe and tolerable dose of NT-I7 (Phase I only)
time frame: Completion of DLT assessment window of Phase I portion of study (estimated to be 8 months)
description: The safe tolerated dose is defined as the dose level immediately below the dose level at which 1 patient of a cohort of 3 patients experiences dose-limiting toxicity within 14 days after administration of NT-I7
Dose limiting toxicities (DLT) are defined as:
A serious adverse event that is at least possibly related to NT-I7
A grade 3 or higher adverse event that is at least possibly related to NT-I7 (excluding injection site swelling, irritation or discomfort)
A clinically significant lab abnormality that is at least possibly related to NT-I7
measure: Percent change in absolute lymphocyte count (ALC)
time frame: From baseline to Day 14
measure: Percent change in absolute lymphocyte count (ALC)
time frame: From baseline through Day 21
measure: Change in SARS-CoV-2 viral load
time frame: From baseline to Day 7
description: -Using PCR from nasopharyngeal swab, oropharyngeal swab or saliva
measure: Change in SARS-CoV-2 viral load
time frame: From baseline to Day 14
description: -Using PCR from nasopharyngeal swab, oropharyngeal swab or saliva
measure: COVID-19 Symptom severity as measured by WHO Ordinal Scale for clinical improvement
time frame: From baseline, day 7, day 14, and day 21
measure: Time to resolution of COVID-19 symptoms
time frame: From baseline through Day 21
measure: Incidence of treatment-emergent adverse events
time frame: From baseline through Day 21
description: -A treatment emergent adverse event (TEAE) is defined as any event that begins or worsens on or after date of first dose of study treatment.
measure: Number of participants by PCR result status (positive or negative)
time frame: -From baseline to Day 7
description: -If quantitative PCR is not available
measure: Number of participants by PCR result status (positive or negative)
time frame: From baseline to Day 14
description: -If quantitative PCR is not available
arm group label: NT-I7 (Phase I)
arm group type: Experimental
description: In the phase I study, 3 dose levels of NT-I7 are planned. Dosing will be staggered such that there will be a minimum of 72 hours between the dosing of one participant and the dosing of the next participant
NT-I7 will be given by intramuscular injection on Day 0
Participants will also be given standard of care treatment for COVID-19
arm group label: NT-I7 (Pilot)
arm group type: Experimental
description: NT-I7 (dose determined by Phase I portion of study) will be given by intramuscular injection on Day 0
Participants will also be given standard of care treatment for COVID-19
arm group label: Placebo (Pilot)
arm group type: Placebo Comparator
description: Placebo will be given by intramuscular injection on Day 0
Participants will also be given standard of care treatment for COVID-19
intervention type: Drug
intervention name: NT-I7
description: Supplied by study
arm group label: NT-I7 (Phase I)
arm group label: NT-I7 (Pilot)
intervention type: Drug
intervention name: Placebo
description: Supplied by study
arm group label: Placebo (Pilot)
intervention type: Procedure
intervention name: Blood for research purposes
description: Prior to injection (Day 0), Day 7, and Day 14
arm group label: NT-I7 (Phase I)
arm group label: NT-I7 (Pilot)
arm group label: Placebo (Pilot)
intervention type: Procedure
intervention name: Blood for pharmacokinetic samples
description: -Phase I only: 1-2 hours prior to dosing, 6 hours after dosing, 24 hours after dosing, Day 7, Day 14, and Day 21
arm group label: NT-I7 (Phase I)
intervention type: Procedure
intervention name: Nasopharyngeal, oropharyngeal, or saliva swab
description: -Prior to study treatment, Day 4(optional), Day 7, and Day 14
arm group label: NT-I7 (Phase I)
arm group label: NT-I7 (Pilot)
arm group label: Placebo (Pilot)
intervention type: Procedure
intervention name: Blood for anti-drug antibody (ADA)
description: Baseline, Day 7, Day 14, Day 21, Day 60, and Day 90. Participants with ADA positivity on Day 90 will be monitored every 90 days until antibody level returns to baseline
arm group label: NT-I7 (Phase I)
arm group label: NT-I7 (Pilot)
arm group label: Placebo (Pilot)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jian Campian, M.D., Ph.D.
role: Principal Investigator
affiliation: Washington University School of Medicine
country: United States
url: http://www.siteman.wustl.edu
description: Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Antibodies
sharing ipd: No