<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/NCT04402957</url>
  </required_header>
  <id_info>
    <org_study_id>AB002</org_study_id>
    <nct_id>NCT04402957</nct_id>
  </id_info>
  <brief_title>LSALT Peptide vs. Placebo to Prevent ARDS and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)</brief_title>
  <official_title>Multicenter, Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study of LSALT Peptide as Prevention of Acute Respiratory Distress Syndrome (ARDS) and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Arch Biopartners Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Arch Biopartners Inc.</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>
      To evaluate the proportion of subjects alive and free of respiratory failure (e.g. need for&#xD;
      non-invasive or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of the&#xD;
      need for continued renal replacement therapy (RRT) on Day 28. The need for continued RRT at&#xD;
      Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR&#xD;
      on Day 28 &lt;10 mL/min/1.73 m2.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a parallel group, randomized, third-party blinded, multicenter study to assess&#xD;
      safety and efficacy of LSALT peptide versus placebo in hospitalized patients with confirmed&#xD;
      infection or recent confirmed infection with complications associated with COVID-19.&#xD;
      Following screening and after establishing baseline parameters such as lung and renal&#xD;
      function, clinical chemistries, coagulation, hematology, and urinalysis, and satisfying all&#xD;
      inclusion and exclusion criteria, patients will be randomized to one of two blinded treatment&#xD;
      regimens:&#xD;
&#xD;
        1. 100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily&#xD;
&#xD;
        2. 100 mL drug-free IV saline infusion over 2 hours daily.&#xD;
&#xD;
      Thirty (30) patients will be randomized to active drug (LSALT peptide) and 30 patients will&#xD;
      be randomized to matching placebo. This study will be third-party blind with only the&#xD;
      Pharmacist at the site unblinded for the purpose of preparing drug/placebo for injection.&#xD;
&#xD;
      Patients will be followed for safety and efficacy up to Day 28, with Day 1 being the day of&#xD;
      randomization to assess safety. After assessing the risk of ARDS and satisfying all inclusion&#xD;
      and exclusion criteria, the patient will be randomized to 5 mg LSALT peptide or blinded&#xD;
      placebo to be given intravenously once daily for a maximum of 14 days. Physical and&#xD;
      respiratory examinations, vital signs, and adverse events will be recorded throughout the&#xD;
      study, including Day 28 (EOS). Blood chemistries, hematology, coagulation, urinalysis, ECG,&#xD;
      SARS-CoV-2 tests, eGFR, and chest x-ray (CXR) will be assessed at Day 1 (Screening/Baseline)&#xD;
      prior to initiation of study drug, and on Day 3, EOT, and at EOS, as well as when clinically&#xD;
      indicated. The ECG at EOS will only be obtained if clinically indicated. An additional CXR&#xD;
      will be obtained at time of clinical improvement. Cytokines/biomarkers and pharmacokinetics&#xD;
      (PK) will be assessed at Day 1 (Screening/Baseline) prior to initiation of study drug, at 1&#xD;
      (mid-dose) and 2 hours (end of infusion) of drug therapy on Days 1, 3, EOT, and a single&#xD;
      blood sample at EOS for cytokines/biomarkers only. Where applicable, a urinary pregnancy test&#xD;
      will be obtained at Screening in women of childbearing potential. Questionnaires (APACHE II,&#xD;
      SOFA) will be obtained at Baseline, Day 3, EOT, and EOS; venous blood gas (VBG) or HCO3&#xD;
      (bicarbonate) levels may be substituted for arterial blood gas (ABG) if it is considered&#xD;
      standard-of-care (SOC) or in the patient's best interest, and results in comparable APACHE II&#xD;
      and SOFA scores. Other questionnaires (Berlin Definition and modified Medical Research&#xD;
      Council Dyspnea Scale) will be assessed at Baseline, Day 3, EOT, and EOS. IgG, IgA, and IgM&#xD;
      antiviral antibodies will be collected at Baseline and EOS. Patients will be maintained on&#xD;
      the SOC per institutional guidelines, including prophylaxis or treatment of VTE, throughout&#xD;
      the study.&#xD;
&#xD;
      A Data and Safety Monitoring Board (DSMB) will evaluate patients on a continuing basis for&#xD;
      primarily safety assessments. Per the DSMB Charter, the DSMB will meet at least monthly if&#xD;
      not more frequently based upon enrollment throughout the study period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 14, 2020</start_date>
  <completion_date type="Actual">June 2, 2022</completion_date>
  <primary_completion_date type="Actual">May 27, 2021</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate the proportion of subjects alive and free of respiratory failure and free of the need for continued renal replacement therapy (RRT) on Day 28 (as per Protocol AB002 - Version 1, dated 09JUNE2020)</measure>
    <time_frame>28 days</time_frame>
    <description>Respiratory failure is defined as the need for non-invasive or invasive mechanical ventilation, high flow oxygen [≥ 6 L/minute], or ECMO. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 &lt;10 mL/min/1.73 m2.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>All-cause mortality</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The presence of and severity of ARDS as an ordinal outcome of the proportion of patients who have none, mild, moderate, or severe ARDS</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to each of mild, moderate, or severe ARDS</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of ventilation-free days and ECMO-free days</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time on nasal cannula or oxygen mask</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of stay in ICU and hospital (admission to discharge)</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Virologic clearance rate</measure>
    <time_frame>28 days</time_frame>
    <description>SARS-CoV2 testing by swab (nasopharyngeal, nasal, throat, sputum, or lower respiratory tract) at baseline (Day 1) and every 3 days thereafter until eradication</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Worst PaO2/FiO2 ratio following enrollment</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PaO2/FiO2 ratio</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vasopressor-free days</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from maximal radiographic damage to EOT</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in baseline modified Medical Research Council (mMRC) score</measure>
    <time_frame>28 days</time_frame>
    <description>Change in mMRC score (0 to 4) with 4 being the most severe outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score</measure>
    <time_frame>28 days</time_frame>
    <description>Change in APACHE II score (0 to 71) with 71 being the most severe outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients with extrapulmonary organ dysfunction using the daily Sequential Organ Failure Assessment (SOFA) score</measure>
    <time_frame>28 days</time_frame>
    <description>Change in SOFA score (0 to 4) with 4 being the most severe outcome</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in liver function by Alanine Aminotransferase (ALT) test</measure>
    <time_frame>28 days</time_frame>
    <description>ALT measured in IU/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in liver function by Aspartate Transferase (AST) test</measure>
    <time_frame>28 days</time_frame>
    <description>AST measured in IU/L</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in liver function by total bilirubin test</measure>
    <time_frame>28 days</time_frame>
    <description>Total bilirubin measured in mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in renal function by serum creatinine (SCr) test</measure>
    <time_frame>28 days</time_frame>
    <description>SCr measured in mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in renal function by estimated Glomerular Filtration Rate (eGFR) test</measure>
    <time_frame>28 days</time_frame>
    <description>eGFR measured in ml/min/1.73m2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in hs-troponin levels</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Activated Coagulation Time (ACT)</measure>
    <time_frame>28 days</time_frame>
    <description>ACT measured in seconds</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in activated Partial Thromboplastin Time (aPTT)</measure>
    <time_frame>28 days</time_frame>
    <description>aPTT measured in seconds</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Prothrombin Time (PT)/International Normalized Ratio (INR)</measure>
    <time_frame>28 days</time_frame>
    <description>PT measured in seconds</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in antiviral IgG, IgA, and IgM levels</measure>
    <time_frame>28 days</time_frame>
    <description>Immunoglobulins measured in mg/dL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total healthcare costs from admission to discharge between treatment groups</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in serum cytokines including IL-1a, IL-1b, and ferritin levels as well as other exploratory biomarkers drawn at the same time as LSALT peptide concentrations</measure>
    <time_frame>28 days</time_frame>
    <description>Fold change from baseline cytokines measured in ng/mL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in baseline antiviral immunoglobulins (IgG, IgM, IgA) at EOS</measure>
    <time_frame>28 days</time_frame>
    <description>Immunoglobulins measured in mg/dL</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">61</enrollment>
  <condition>COVID</condition>
  <condition>Severe Acute Respiratory Syndrome</condition>
  <condition>Sars-CoV2</condition>
  <condition>Acute Kidney Injury</condition>
  <condition>Acute Respiratory Distress Syndrome</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>100 mL drug-free IV saline infusion over 2 hours daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>LSALT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>LSALT peptide</intervention_name>
    <description>LSALT, a peptide drug with the sequence NH3-LSALTPSPSWLKYKAL-COOH, binds to dipeptidase-1 (DPEP-1) but does not inhibit its biologic enzymatic activity. LSALT peptide inhibits leukocyte recruitment in multiple experimental disease models through the direct inhibition of leukocyte adhesion to DPEP-1 present in lungs, kidney, and liver.</description>
    <arm_group_label>LSALT</arm_group_label>
    <other_name>Metablok</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>0.9% saline solution</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria (Amendment 3, 15FEB2021):&#xD;
&#xD;
          1. Male and female hospitalized patients between 18 and 80 years of age at time of&#xD;
             consent.&#xD;
&#xD;
          2. Clinical and laboratory diagnosis of COVID-19 infection. Patients must be positive for&#xD;
             the SARS-CoV-2 by Real-Time Reverse Transcriptase (RT)-PCR&#xD;
&#xD;
             Diagnostic Panel or have an existing complication secondary to SARS-CoV-2 infection&#xD;
             which was positive within 2 weeks of entry into the study. Further, patients must have&#xD;
             at least two of the following three symptoms:&#xD;
&#xD;
               -  Fever (oral temperature ≥ 100.4 °F [&gt; 38 °C]) with or without chills&#xD;
&#xD;
               -  Dyspnea or difficulty breathing (≤ 2 on mMRC dyspnea scale)&#xD;
&#xD;
               -  Nonproductive cough&#xD;
&#xD;
               -  Or other signs and symptoms of established complications to SARS-CoV-2 infection&#xD;
                  (e.g. coagulopathy, cardiomyopathy, acute kidney injury, and/or acute liver&#xD;
                  injury) within the limits of Exclusion Criteria 8&#xD;
&#xD;
          3. Patients must present with moderate to severe illness as defined below:&#xD;
&#xD;
               -  Moderate illness: Patients who have evidence of lower respiratory disease by&#xD;
                  clinical assessment or imaging and an oxygen saturation (SpO2) &gt; 93% on room air&#xD;
                  at sea level&#xD;
&#xD;
               -  Severe illness: Patients who have a respiratory frequency &gt; 30 breaths per minute&#xD;
                  (bpm), SpO2 ≤ 93% on room air at sea level, ratio of arterial partial pressure of&#xD;
                  oxygen to fraction of inspired oxygen (PaO2/FiO2) &lt; 300, or lung infiltrates &gt;&#xD;
                  50%.&#xD;
&#xD;
          4. APACHE II score &lt; 20 or establishment of survivability of the patient beyond 48 hours&#xD;
             following randomization&#xD;
&#xD;
          5. Therapies which have been shown to be beneficial and are included in standard COVID-19&#xD;
             treatment guidelines (e.g. those of WHO or NIH, or institutional guidelines) are&#xD;
             permitted&#xD;
&#xD;
          6. Sexually active women of child-bearing potential (WCBP) must be using a medically&#xD;
             acceptable method of birth control throughout the study and for at least 1 day&#xD;
             following the end of study, and have a negative urine pregnancy test at the Screening&#xD;
             visit. A WCBP is defined as a female who is biologically capable of becoming pregnant.&#xD;
             A medically acceptable method of birth control includes intrauterine devices in place&#xD;
             for at least 3 months, surgical sterilization, or the implant. In patients who are not&#xD;
             sexually active, abstinence is an acceptable form of birth control and urine will be&#xD;
             tested per protocol. Women who are of nonchild-bearing potential, i.e.,&#xD;
             post-menopause, must have this condition captured in their medical history. Pregnant&#xD;
             women and nursing mothers are excluded from this study.&#xD;
&#xD;
          7. Patient or LAR is available and willing to give written informed consent, after being&#xD;
             properly informed of the nature and risks of the study and prior to engaging in any&#xD;
             study-related procedures.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known sensitivity, allergy, or previous exposure to LSALT peptide.&#xD;
&#xD;
          2. Exposure to any investigational drug or device &lt;90 days prior to entry into study.&#xD;
&#xD;
          3. Treatment with immunomodulators or immunosuppressant drugs, including but not limited&#xD;
             to IL-6 inhibitors, TNF inhibitors, anti-IL-1 immunomodulators, and JAK inhibitors&#xD;
             within five half-lives or 30 days (whichever is longer) prior to randomization and&#xD;
             throughout the study period. However, should any of these treatments become&#xD;
             standard-of-care and incorporated into clinical treatment guidelines (e.g. those of&#xD;
             WHO or NIH), the treatment is permitted. Further, low-dose oral prednisone (&lt;20&#xD;
             mg/day) and inhaled steroids (e.g. treatment of asthma) are allowed in the study.&#xD;
&#xD;
          4. Anticipated transfer to another hospital or medical center within 72 hours, which is&#xD;
             not a study site.&#xD;
&#xD;
          5. Uncontrolled of poorly treated active hepatitis B (HBV), hepatitis C (HepC), or HIV&#xD;
             infection. Those subjects who are positive for HBV, HepC, or HIV but are&#xD;
             well-controlled with low viral loads are allowed to participate in this study:&#xD;
&#xD;
               -  HBV low viral load defined as &lt;20,000 IU/mL&#xD;
&#xD;
               -  HepC low viral load defined as &lt;800,000 IU/mL&#xD;
&#xD;
               -  HIV low viral load defined as &lt;5000 copies/mL&#xD;
&#xD;
          6. Participation in another drug or device study at any time during this study, for&#xD;
             example:&#xD;
&#xD;
               -  Ulinastatin 200,000 IU or greater&#xD;
&#xD;
               -  High dose intravenous Vitamin C&#xD;
&#xD;
               -  Budesonide and formoterol&#xD;
&#xD;
               -  Bevacizumab to prevent ARDS&#xD;
&#xD;
               -  Dornase alfa to reduce hypoxemia in ventilated trauma patients.&#xD;
&#xD;
          7. As indicated in the inclusion criteria, pregnant female patients are excluded from&#xD;
             study. Further, female patients who are nursing are excluded from study.&#xD;
&#xD;
          8. Has any medical condition considered to be clinically significant and could&#xD;
             potentially affect patient safety or study outcome, including but not limited to:&#xD;
&#xD;
               -  Acute or chronic kidney disease (stage-4 or -5 renal impairment; eGFR&lt;30&#xD;
                  mL/min/1.73 m2 or hemodialysis)&#xD;
&#xD;
               -  End-stage malignancy undergoing treatment&#xD;
&#xD;
               -  Immunocompromised patients or those with medical/surgical conditions (e.g., solid&#xD;
                  organ transplantation) which require chronic immunosuppression&#xD;
&#xD;
               -  Chronic hematologic disease which, in the opinion of the PI, prohibits the&#xD;
                  patient from entering into study&#xD;
&#xD;
               -  Acute liver injury with AST and/or ALT levels greater than 3x ULN unless recent&#xD;
                  injury (within 2 weeks) likely due to COVID-19 infection&#xD;
&#xD;
               -  History of coagulopathy within the last year as defined by abnormal ACT, aPTT,&#xD;
                  and/or PT/INR values at least 2-fold outside normal limits, and currently present&#xD;
                  at screening, and/or&#xD;
&#xD;
               -  End-stage lung disease, acute lung injury, severe chronic obstructive pulmonary&#xD;
                  disease (COPD) as assessed by the GOLD criteria (GOLD Stage IV), or mechanical&#xD;
                  ventilation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>VA San Diego Healthcare System</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Broward Health Medical Center</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33316</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LSU Health Shreveport</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Calgary - Foothills Medical Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Calgary - Peter Lougheed Centre</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ankara City Hospital</name>
      <address>
        <city>Ankara</city>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istanbul University Cerrahpasa</name>
      <address>
        <city>Istanbul</city>
        <zip>34098</zip>
        <country>Turkey</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>Turkey</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>May 12, 2020</study_first_submitted>
  <study_first_submitted_qc>May 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 27, 2020</study_first_posted>
  <last_update_submitted>April 14, 2023</last_update_submitted>
  <last_update_submitted_qc>April 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Severe Acute Respiratory Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome</mesh_term>
    <mesh_term>Respiratory Distress Syndrome, Newborn</mesh_term>
    <mesh_term>Acute Lung Injury</mesh_term>
    <mesh_term>Acute Kidney Injury</mesh_term>
    <mesh_term>Syndrome</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04402957
org study id: AB002
nct id: NCT04402957
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
To evaluate the proportion of subjects alive and free of respiratory failure (e.g. need for
      non-invasive or invasive mechanical ventilation, high flow oxygen, or ECMO) and free of the
      need for continued renal replacement therapy (RRT) on Day 28. The need for continued RRT at
      Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR
      on Day 28 <10 mL/min/1.73 m2.
This study is a parallel group, randomized, third-party blinded, multicenter study to assess
      safety and efficacy of LSALT peptide versus placebo in hospitalized patients with confirmed
      infection or recent confirmed infection with complications associated with COVID-19.
      Following screening and after establishing baseline parameters such as lung and renal
      function, clinical chemistries, coagulation, hematology, and urinalysis, and satisfying all
      inclusion and exclusion criteria, patients will be randomized to one of two blinded treatment
      regimens:

        1. 100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily

        2. 100 mL drug-free IV saline infusion over 2 hours daily.

      Thirty (30) patients will be randomized to active drug (LSALT peptide) and 30 patients will
      be randomized to matching placebo. This study will be third-party blind with only the
      Pharmacist at the site unblinded for the purpose of preparing drug/placebo for injection.

      Patients will be followed for safety and efficacy up to Day 28, with Day 1 being the day of
      randomization to assess safety. After assessing the risk of ARDS and satisfying all inclusion
      and exclusion criteria, the patient will be randomized to 5 mg LSALT peptide or blinded
      placebo to be given intravenously once daily for a maximum of 14 days. Physical and
      respiratory examinations, vital signs, and adverse events will be recorded throughout the
      study, including Day 28 (EOS). Blood chemistries, hematology, coagulation, urinalysis, ECG,
      SARS-CoV-2 tests, eGFR, and chest x-ray (CXR) will be assessed at Day 1 (Screening/Baseline)
      prior to initiation of study drug, and on Day 3, EOT, and at EOS, as well as when clinically
      indicated. The ECG at EOS will only be obtained if clinically indicated. An additional CXR
      will be obtained at time of clinical improvement. Cytokines/biomarkers and pharmacokinetics
      (PK) will be assessed at Day 1 (Screening/Baseline) prior to initiation of study drug, at 1
      (mid-dose) and 2 hours (end of infusion) of drug therapy on Days 1, 3, EOT, and a single
      blood sample at EOS for cytokines/biomarkers only. Where applicable, a urinary pregnancy test
      will be obtained at Screening in women of childbearing potential. Questionnaires (APACHE II,
      SOFA) will be obtained at Baseline, Day 3, EOT, and EOS; venous blood gas (VBG) or HCO3
      (bicarbonate) levels may be substituted for arterial blood gas (ABG) if it is considered
      standard-of-care (SOC) or in the patient's best interest, and results in comparable APACHE II
      and SOFA scores. Other questionnaires (Berlin Definition and modified Medical Research
      Council Dyspnea Scale) will be assessed at Baseline, Day 3, EOT, and EOS. IgG, IgA, and IgM
      antiviral antibodies will be collected at Baseline and EOS. Patients will be maintained on
      the SOC per institutional guidelines, including prophylaxis or treatment of VTE, throughout
      the study.

      A Data and Safety Monitoring Board (DSMB) will evaluate patients on a continuing basis for
      primarily safety assessments. Per the DSMB Charter, the DSMB will meet at least monthly if
      not more frequently based upon enrollment throughout the study period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: To evaluate the proportion of subjects alive and free of respiratory failure and free of the need for continued renal replacement therapy (RRT) on Day 28 (as per Protocol AB002 - Version 1, dated 09JUNE2020)
time frame: 28 days
description: Respiratory failure is defined as the need for non-invasive or invasive mechanical ventilation, high flow oxygen [≥ 6 L/minute], or ECMO. The need for continued RRT at Day 28 will be defined as either dialysis in the past 3 days (Day 26, 27, or 28) or an eGFR on Day 28 <10 mL/min/1.73 m2.
measure: All-cause mortality
time frame: 28 days
measure: The presence of and severity of ARDS as an ordinal outcome of the proportion of patients who have none, mild, moderate, or severe ARDS
time frame: 28 days
measure: Time to each of mild, moderate, or severe ARDS
time frame: 28 days
measure: The number of ventilation-free days and ECMO-free days
time frame: 28 days
measure: Time on nasal cannula or oxygen mask
time frame: 28 days
measure: Length of stay in ICU and hospital (admission to discharge)
time frame: 28 days
measure: Virologic clearance rate
time frame: 28 days
description: SARS-CoV2 testing by swab (nasopharyngeal, nasal, throat, sputum, or lower respiratory tract) at baseline (Day 1) and every 3 days thereafter until eradication
measure: Worst PaO2/FiO2 ratio following enrollment
time frame: 28 days
measure: Change in PaO2/FiO2 ratio
time frame: 28 days
measure: Vasopressor-free days
time frame: 28 days
measure: Change from maximal radiographic damage to EOT
time frame: 28 days
measure: Change in baseline modified Medical Research Council (mMRC) score
time frame: 28 days
description: Change in mMRC score (0 to 4) with 4 being the most severe outcome
measure: Change in Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II score
time frame: 28 days
description: Change in APACHE II score (0 to 71) with 71 being the most severe outcome
measure: Proportion of patients with extrapulmonary organ dysfunction using the daily Sequential Organ Failure Assessment (SOFA) score
time frame: 28 days
description: Change in SOFA score (0 to 4) with 4 being the most severe outcome
measure: Change in liver function by Alanine Aminotransferase (ALT) test
time frame: 28 days
description: ALT measured in IU/L
measure: Change in liver function by Aspartate Transferase (AST) test
time frame: 28 days
description: AST measured in IU/L
measure: Change in liver function by total bilirubin test
time frame: 28 days
description: Total bilirubin measured in mg/dL
measure: Change in renal function by serum creatinine (SCr) test
time frame: 28 days
description: SCr measured in mg/dL
measure: Change in renal function by estimated Glomerular Filtration Rate (eGFR) test
time frame: 28 days
description: eGFR measured in ml/min/1.73m2
measure: Change in hs-troponin levels
time frame: 28 days
measure: Change in Activated Coagulation Time (ACT)
time frame: 28 days
description: ACT measured in seconds
measure: Change in activated Partial Thromboplastin Time (aPTT)
time frame: 28 days
description: aPTT measured in seconds
measure: Change in Prothrombin Time (PT)/International Normalized Ratio (INR)
time frame: 28 days
description: PT measured in seconds
measure: Change in antiviral IgG, IgA, and IgM levels
time frame: 28 days
description: Immunoglobulins measured in mg/dL
measure: Total healthcare costs from admission to discharge between treatment groups
time frame: 28 days
measure: Change in serum cytokines including IL-1a, IL-1b, and ferritin levels as well as other exploratory biomarkers drawn at the same time as LSALT peptide concentrations
time frame: 28 days
description: Fold change from baseline cytokines measured in ng/mL
measure: Change in baseline antiviral immunoglobulins (IgG, IgM, IgA) at EOS
time frame: 28 days
description: Immunoglobulins measured in mg/dL
arm group label: Placebo
arm group type: Placebo Comparator
description: 100 mL drug-free IV saline infusion over 2 hours daily
arm group label: LSALT
arm group type: Experimental
description: 100 mL of 5 mg IV LSALT peptide infusion over 2 hours daily
intervention type: Drug
intervention name: LSALT peptide
description: LSALT, a peptide drug with the sequence NH3-LSALTPSPSWLKYKAL-COOH, binds to dipeptidase-1 (DPEP-1) but does not inhibit its biologic enzymatic activity. LSALT peptide inhibits leukocyte recruitment in multiple experimental disease models through the direct inhibition of leukocyte adhesion to DPEP-1 present in lungs, kidney, and liver.
arm group label: LSALT
other name: Metablok
intervention type: Drug
intervention name: Placebo
description: 0.9% saline solution
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Canada
country: Turkey
country: United States
responsible party type: Sponsor
mesh term: Severe Acute Respiratory Syndrome
mesh term: Respiratory Distress Syndrome
mesh term: Respiratory Distress Syndrome, Newborn
mesh term: Acute Lung Injury
mesh term: Acute Kidney Injury
mesh term: Syndrome
mesh term: Wounds and Injuries
sharing ipd: Undecided