LSALT Peptide vs. Placebo to Prevent ARDS and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)
Condition: COVID; Severe Acute Respiratory Syndrome; Sars-CoV2; Acute Kidney Injury; Acute Respiratory Distress Syndrome
MeSH terms: Severe Acute Respiratory Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Acute Kidney Injury; Syndrome; Wounds and Injuries
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): LSALT peptide; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 0.9% saline solution
Other intervention name(s): Metablok
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment