<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/NCT04428008</url>
  </required_header>
  <id_info>
    <org_study_id>ACW-1221958-1</org_study_id>
    <nct_id>NCT04428008</nct_id>
  </id_info>
  <brief_title>Thymosin Alpha 1 to Prevent COVID-19 Infection in Renal Dialysis Patients</brief_title>
  <acronym>Ta1</acronym>
  <official_title>A Pilot Trial of Thymalfasin (Ta1) to Prevent COVID-19 Infection in Renal Dialysis Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>William B. Ershler, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Davita Clinical Research</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Clinical Research Consultants, LLC</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ershler, William B., MD</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>
      Thymalfasin (thymosin alpha 1 or Ta1), the active pharmaceutical ingredient in ZADAXIN®&#xD;
      injection, is a 28-amino acid synthetic peptide, identical to natural Ta1 produced by the&#xD;
      thymus gland. Ta1 is a biological response modifier which activates various cells of the&#xD;
      immune system, and is therefore expected to have clinical benefits in disorders where immune&#xD;
      responses are impaired or ineffective, including acute and chronic viral and bacterial&#xD;
      infections, cancers, and vaccine non-responsiveness. Patients with end-stage renal disease&#xD;
      (ESRD) on hemodialysis, in addition to their intrinsic kidney disease and frequent burden of&#xD;
      comorbidities, also have increased risk of exposure to communicable diseases as they are&#xD;
      treated several times each week at hemodialysis centers with several other patients and&#xD;
      clinic staff in attendance. The majority of patients are over 60 years of age and many are&#xD;
      receiving immunosuppressive medications. Accordingly, ESRD patients are particularly&#xD;
      susceptible to COVID-19 infection. Ta1 has been shown to be safely administered to&#xD;
      hemodialysis patients. It is our hypothesis that a course of Ta1 administered to individuals&#xD;
      with ESRD will reduce the rate and severity of infection with COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients with end-stage renal disease (ESRD) on hemodialysis, in addition to their intrinsic&#xD;
      kidney disease and frequent burden of comorbidities, also have increased risk of exposure to&#xD;
      communicable diseases as they are treated several times each week at hemodialysis centers&#xD;
      with several other patients and clinic staff in attendance. The majority of patients are over&#xD;
      60 years of age and many are receiving immunosuppressive medications. Accordingly, ESRD&#xD;
      patients are particularly susceptible to COVID-19 infection.&#xD;
&#xD;
      Thymalfasin (thymosin alpha 1, Ta1) is a naturally occurring peptide that has been evaluated&#xD;
      for its immunomodulatory activities and related therapeutic potential in several conditions&#xD;
      and diseases, including infectious disease and cancer. ZADAXIN, a synthetic form of Ta1, been&#xD;
      has been used clinically in pilot studies for treatment of severe acute respiratory syndrome&#xD;
      (SARS) and other lung infections including acute respiratory distress syndrome (ARDS) and&#xD;
      chronic obstructive pulmonary disorder (COPD), as well as infections after bone marrow&#xD;
      transplant]. Larger clinical trials have shown significant efficacy for treatment of severe&#xD;
      sepsis and hepatitis B, along with certain cancers such as melanoma, hepatocellular, and lung&#xD;
      cancer. Ta1 has also demonstrated improvement in response to vaccines in the elderly and in&#xD;
      patients immunocompromised by renal disease. The beneficial clinical effects of Ta1 result&#xD;
      from activation of toll-like receptor (TLR) 9 in dendritic and other immune system cells,&#xD;
      resulting in augmentation of T helper (Th1) function, natural killer (NK) cell activity, and&#xD;
      increased antibody responses to T-cell dependent antigens. Importantly, Ta1 also leads to an&#xD;
      increase in IL-10 producing regulatory T cells, which create feedback inhibition of cytokine&#xD;
      production, hence dampening immune response and preventing a pro-inflammatory cytokine storm.&#xD;
&#xD;
      It is our hypothesis that a course of Ta1 administered to individuals at high risk for&#xD;
      COVID-19 infection (hemodialysis patients) will reduce the rate of COVID-19 infection and&#xD;
      severity of infection with COVID-19, compared to untreated individuals in the same&#xD;
      hemodialysis units with comparable risk. The study will also evaluate the need for&#xD;
      hospitalization in those patients who do not become infected with COVID-19.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">January 12, 2021</start_date>
  <completion_date type="Anticipated">February 2023</completion_date>
  <primary_completion_date type="Anticipated">October 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>Subjects will be centrally randomized to receive either study treatment drug (Ta1) or no Ta1. Randomization will be stratified by site.</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Reduction in documented infection with COVID-19 Reduction in infection with COVID-19</measure>
    <time_frame>6 months</time_frame>
    <description>Number of subjects who become infected with COVID-19 over the course of the study</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Need for hospitalization</measure>
    <time_frame>6 months</time_frame>
    <description>Number of subjects who become hospitalized</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>6 months</time_frame>
    <description>If subject becomes hospitalized, what length of time does the subject remain hospitalized</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for ICU admission</measure>
    <time_frame>6 months</time_frame>
    <description>Number of subjects who are entered into the ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>6 months</time_frame>
    <description>If subject is entered into the ICU, what length of time does the subject remain in the ICU</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Need for mechanical ventilation</measure>
    <time_frame>6 months</time_frame>
    <description>Number of subjects who require mechanical ventilation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of mechanical ventilation</measure>
    <time_frame>6 months</time_frame>
    <description>If mechanical ventilation is required, what length of time the ventilation is required</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Recovery time from COVID-19</measure>
    <time_frame>6 months</time_frame>
    <description>If subject becomes infected with COVID-19, how long does the subject require to recover from the infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in any existing comorbidities or occurrence of newly diagnosed disease</measure>
    <time_frame>6 months</time_frame>
    <description>Evaluation of whether any comorbidities are changed over the course of treatment (eg., worsening of congestive heart failure)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of non-COVID-19 infections</measure>
    <time_frame>6 months</time_frame>
    <description>Determination of whether there are more or fewer infections other than COVID-19 (other respiratory, urinary tract, cellulitis, etc.)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in lymphocyte subsets (CD4, CD8)</measure>
    <time_frame>6 months</time_frame>
    <description>Evaluation of the levels of CD4 and CD8 subjects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>6 months</time_frame>
    <description>Number of subjects who die during the course of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-emergent adverse events</measure>
    <time_frame>6 months</time_frame>
    <description>Number of subjects with mild, moderate, or severe adverse events based on perceived clinical significance of the event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-emergent changes in vital signs</measure>
    <time_frame>6 months</time_frame>
    <description>Number of subjects with mild, moderate, or severe changes to vital signs based on perceived clinical significance of the event</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment-emergent laboratory parameters</measure>
    <time_frame>6 months</time_frame>
    <description>Number of subjects with mild, moderate, or severe laboratory findings based on perceived clinical significance of the event</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">262</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Active arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1.6 mg thymalfasin in 1 mL subcutaneous injection twice weekly after dialysis for 8 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control arm</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Standard care</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Thymalfasin</intervention_name>
    <description>Synthetic 28 amino acid peptide</description>
    <arm_group_label>Active arm</arm_group_label>
    <other_name>Thymosin alpha 1</other_name>
    <other_name>Ta1</other_name>
    <other_name>ZADAXIN</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 18 or greater&#xD;
&#xD;
          -  Signed informed consent&#xD;
&#xD;
          -  End-stage renal disease (ESRD) who receive hemodialysis 2 or more times each week and&#xD;
             are expected to continue on dialysis indefinitely.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients on short-term hemodialysis, such as those with transient renal dysfunction&#xD;
             associated with acute illness who are projected to have return in renal function&#xD;
&#xD;
          -  Patients for whom renal transplantation is anticipated within the next six months&#xD;
&#xD;
          -  Patients with an anticipated survival of less than 3 months&#xD;
&#xD;
          -  Patients with symptoms that might be attributable to COVID-19 infection&#xD;
&#xD;
          -  Patients who test positive for SARS-CoV2&#xD;
&#xD;
          -  Patients with active infectious disease requiring antibiotics&#xD;
&#xD;
          -  Patients with hospitalization within the previous 3 months for acute myocardial&#xD;
             infarction or congestive heart failure&#xD;
&#xD;
          -  Patients with advanced malignancy receiving cytotoxic chemotherapy&#xD;
&#xD;
          -  Patients with a Karnofsky Performance Scale score of less than 60&#xD;
&#xD;
          -  Patients with prior history of solid organ (kidney, liver, heart, lung, pancreas) or&#xD;
             bone marrow transplant&#xD;
&#xD;
          -  Patients with active autoimmune disease on immunosuppressive medication&#xD;
&#xD;
          -  Patients receiving Plaquenil&#xD;
&#xD;
          -  Participation in an investigational drug or device trial in previous 30 days&#xD;
&#xD;
          -  History of allergy or intolerance to Ta1&#xD;
&#xD;
          -  Any other medical or psychiatric condition that, in the opinion of the Investigator,&#xD;
             would compromise patient safety or interfere with the objectives of the protocol or&#xD;
             completion of the protocol treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Clinical Research Consultants</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>64111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>June 7, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>September 24, 2022</last_update_submitted>
  <last_update_submitted_qc>September 24, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ershler, William B., MD</investigator_affiliation>
    <investigator_full_name>William B. Ershler, MD</investigator_full_name>
    <investigator_title>Ershler, William B., MD</investigator_title>
  </responsible_party>
  <keyword>COVID-19</keyword>
  <keyword>Thymalfasin</keyword>
  <keyword>Thymosin alpha 1</keyword>
  <keyword>ZADAXIN</keyword>
  <keyword>Hemodialysis</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>Thymalfasin</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/NCT04428008
org study id: ACW-1221958-1
nct id: NCT04428008
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Thymalfasin (thymosin alpha 1 or Ta1), the active pharmaceutical ingredient in ZADAXIN®
      injection, is a 28-amino acid synthetic peptide, identical to natural Ta1 produced by the
      thymus gland. Ta1 is a biological response modifier which activates various cells of the
      immune system, and is therefore expected to have clinical benefits in disorders where immune
      responses are impaired or ineffective, including acute and chronic viral and bacterial
      infections, cancers, and vaccine non-responsiveness. Patients with end-stage renal disease
      (ESRD) on hemodialysis, in addition to their intrinsic kidney disease and frequent burden of
      comorbidities, also have increased risk of exposure to communicable diseases as they are
      treated several times each week at hemodialysis centers with several other patients and
      clinic staff in attendance. The majority of patients are over 60 years of age and many are
      receiving immunosuppressive medications. Accordingly, ESRD patients are particularly
      susceptible to COVID-19 infection. Ta1 has been shown to be safely administered to
      hemodialysis patients. It is our hypothesis that a course of Ta1 administered to individuals
      with ESRD will reduce the rate and severity of infection with COVID-19.
Patients with end-stage renal disease (ESRD) on hemodialysis, in addition to their intrinsic
      kidney disease and frequent burden of comorbidities, also have increased risk of exposure to
      communicable diseases as they are treated several times each week at hemodialysis centers
      with several other patients and clinic staff in attendance. The majority of patients are over
      60 years of age and many are receiving immunosuppressive medications. Accordingly, ESRD
      patients are particularly susceptible to COVID-19 infection.

      Thymalfasin (thymosin alpha 1, Ta1) is a naturally occurring peptide that has been evaluated
      for its immunomodulatory activities and related therapeutic potential in several conditions
      and diseases, including infectious disease and cancer. ZADAXIN, a synthetic form of Ta1, been
      has been used clinically in pilot studies for treatment of severe acute respiratory syndrome
      (SARS) and other lung infections including acute respiratory distress syndrome (ARDS) and
      chronic obstructive pulmonary disorder (COPD), as well as infections after bone marrow
      transplant]. Larger clinical trials have shown significant efficacy for treatment of severe
      sepsis and hepatitis B, along with certain cancers such as melanoma, hepatocellular, and lung
      cancer. Ta1 has also demonstrated improvement in response to vaccines in the elderly and in
      patients immunocompromised by renal disease. The beneficial clinical effects of Ta1 result
      from activation of toll-like receptor (TLR) 9 in dendritic and other immune system cells,
      resulting in augmentation of T helper (Th1) function, natural killer (NK) cell activity, and
      increased antibody responses to T-cell dependent antigens. Importantly, Ta1 also leads to an
      increase in IL-10 producing regulatory T cells, which create feedback inhibition of cytokine
      production, hence dampening immune response and preventing a pro-inflammatory cytokine storm.

      It is our hypothesis that a course of Ta1 administered to individuals at high risk for
      COVID-19 infection (hemodialysis patients) will reduce the rate of COVID-19 infection and
      severity of infection with COVID-19, compared to untreated individuals in the same
      hemodialysis units with comparable risk. The study will also evaluate the need for
      hospitalization in those patients who do not become infected with COVID-19.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Subjects will be centrally randomized to receive either study treatment drug (Ta1) or no Ta1. Randomization will be stratified by site.
primary purpose: Prevention
masking: None (Open Label)
measure: Reduction in documented infection with COVID-19 Reduction in infection with COVID-19
time frame: 6 months
description: Number of subjects who become infected with COVID-19 over the course of the study
measure: Need for hospitalization
time frame: 6 months
description: Number of subjects who become hospitalized
measure: Hospital length of stay
time frame: 6 months
description: If subject becomes hospitalized, what length of time does the subject remain hospitalized
measure: Need for ICU admission
time frame: 6 months
description: Number of subjects who are entered into the ICU
measure: ICU length of stay
time frame: 6 months
description: If subject is entered into the ICU, what length of time does the subject remain in the ICU
measure: Need for mechanical ventilation
time frame: 6 months
description: Number of subjects who require mechanical ventilation
measure: Duration of mechanical ventilation
time frame: 6 months
description: If mechanical ventilation is required, what length of time the ventilation is required
measure: Recovery time from COVID-19
time frame: 6 months
description: If subject becomes infected with COVID-19, how long does the subject require to recover from the infection
measure: Change in any existing comorbidities or occurrence of newly diagnosed disease
time frame: 6 months
description: Evaluation of whether any comorbidities are changed over the course of treatment (eg., worsening of congestive heart failure)
measure: Incidence of non-COVID-19 infections
time frame: 6 months
description: Determination of whether there are more or fewer infections other than COVID-19 (other respiratory, urinary tract, cellulitis, etc.)
measure: Change in lymphocyte subsets (CD4, CD8)
time frame: 6 months
description: Evaluation of the levels of CD4 and CD8 subjects
measure: Mortality
time frame: 6 months
description: Number of subjects who die during the course of the study
measure: Treatment-emergent adverse events
time frame: 6 months
description: Number of subjects with mild, moderate, or severe adverse events based on perceived clinical significance of the event
measure: Treatment-emergent changes in vital signs
time frame: 6 months
description: Number of subjects with mild, moderate, or severe changes to vital signs based on perceived clinical significance of the event
measure: Treatment-emergent laboratory parameters
time frame: 6 months
description: Number of subjects with mild, moderate, or severe laboratory findings based on perceived clinical significance of the event
arm group label: Active arm
arm group type: Experimental
description: 1.6 mg thymalfasin in 1 mL subcutaneous injection twice weekly after dialysis for 8 weeks
arm group label: Control arm
arm group type: No Intervention
description: Standard care
intervention type: Drug
intervention name: Thymalfasin
description: Synthetic 28 amino acid peptide
arm group label: Active arm
other name: Thymosin alpha 1
other name: Ta1
other name: ZADAXIN
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Ershler, William B., MD
investigator full name: William B. Ershler, MD
investigator title: Ershler, William B., MD
mesh term: COVID-19
mesh term: Thymalfasin
sharing ipd: No