LSALT Peptide vs. Placebo to Prevent ARDS and Acute Kidney Injury in Patients Infected With SARS-CoV-2 (COVID-19)

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:

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

Inclusion criteria

(Amendment 3, 15FEB2021):

• Male and female hospitalized patients between 18 and 80 years of age at time of consent.
• Clinical and laboratory diagnosis of COVID-19 infection. Patients must be positive for the SARS-CoV-2 by Real-Time Reverse Transcriptase (RT)-PCR

Diagnostic Panel or have an existing complication secondary to SARS-CoV-2 infection which was positive within 2 weeks of entry into the study. Further, patients must have at least two of the following three symptoms:

• Fever (oral temperature ≥ 100.4 °F [> 38 °C]) with or without chills
• Dyspnea or difficulty breathing (≤ 2 on mMRC dyspnea scale)
• Nonproductive cough
• Or other signs and symptoms of established complications to SARS-CoV-2 infection (e.g. coagulopathy, cardiomyopathy, acute kidney injury, and/or acute liver injury) within the limits of Exclusion Criteria 8
• Patients must present with moderate to severe illness as defined below:

• Moderate illness: Patients who have evidence of lower respiratory disease by clinical assessment or imaging and an oxygen saturation (SpO2) > 93% on room air at sea level
• Severe illness: Patients who have a respiratory frequency > 30 breaths per minute (bpm), SpO2 ≤ 93% on room air at sea level, ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) < 300, or lung infiltrates > 50%.
• APACHE II score < 20 or establishment of survivability of the patient beyond 48 hours following randomization
• Therapies which have been shown to be beneficial and are included in standard COVID-19 treatment guidelines (e.g. those of WHO or NIH, or institutional guidelines) are permitted
• Sexually active women of child-bearing potential (WCBP) must be using a medically acceptable method of birth control throughout the study and for at least 1 day following the end of study, and have a negative urine pregnancy test at the Screening visit. A WCBP is defined as a female who is biologically capable of becoming pregnant. A medically acceptable method of birth control includes intrauterine devices in place for at least 3 months, surgical sterilization, or the implant. In patients who are not sexually active, abstinence is an acceptable form of birth control and urine will be tested per protocol. Women who are of nonchild-bearing potential, i.e., post-menopause, must have this condition captured in their medical history. Pregnant women and nursing mothers are excluded from this study.
• Patient or LAR is available and willing to give written informed consent, after being properly informed of the nature and risks of the study and prior to engaging in any study-related procedures.

Exclusion criteria

• Known sensitivity, allergy, or previous exposure to LSALT peptide.
• Exposure to any investigational drug or device <90 days prior to entry into study.
• Treatment with immunomodulators or immunosuppressant drugs, including but not limited to IL-6 inhibitors, TNF inhibitors, anti-IL-1 immunomodulators, and JAK inhibitors within five half-lives or 30 days (whichever is longer) prior to randomization and throughout the study period. However, should any of these treatments become standard-of-care and incorporated into clinical treatment guidelines (e.g. those of WHO or NIH), the treatment is permitted. Further, low-dose oral prednisone (<20 mg/day) and inhaled steroids (e.g. treatment of asthma) are allowed in the study.
• Anticipated transfer to another hospital or medical center within 72 hours, which is not a study site.
• Uncontrolled of poorly treated active hepatitis B (HBV), hepatitis C (HepC), or HIV infection. Those subjects who are positive for HBV, HepC, or HIV but are well-controlled with low viral loads are allowed to participate in this study:

• HBV low viral load defined as <20,000 IU/mL
• HepC low viral load defined as <800,000 IU/mL
• HIV low viral load defined as <5000 copies/mL
• Participation in another drug or device study at any time during this study, for example:

• Ulinastatin 200,000 IU or greater
• High dose intravenous Vitamin C
• Budesonide and formoterol
• Bevacizumab to prevent ARDS
• Dornase alfa to reduce hypoxemia in ventilated trauma patients.
• As indicated in the inclusion criteria, pregnant female patients are excluded from study. Further, female patients who are nursing are excluded from study.
• Has any medical condition considered to be clinically significant and could potentially affect patient safety or study outcome, including but not limited to:

• Acute or chronic kidney disease (stage-4 or -5 renal impairment; eGFR<30 mL/min/1.73 m2 or hemodialysis)
• End-stage malignancy undergoing treatment
• Immunocompromised patients or those with medical/surgical conditions (e.g., solid organ transplantation) which require chronic immunosuppression
• Chronic hematologic disease which, in the opinion of the PI, prohibits the patient from entering into study
• Acute liver injury with AST and/or ALT levels greater than 3x ULN unless recent injury (within 2 weeks) likely due to COVID-19 infection
• History of coagulopathy within the last year as defined by abnormal ACT, aPTT, and/or PT/INR values at least 2-fold outside normal limits, and currently present at screening, and/or
• End-stage lung disease, acute lung injury, severe chronic obstructive pulmonary disease (COPD) as assessed by the GOLD criteria (GOLD Stage IV), or mechanical ventilation.