Intervention: Razuprotafib
Trial phase: Phase 2
SMILES: COC(=O)N[C@@H](Cc1ccccc1)C(=O)N[C@@H](Cc1ccc(NS(=O)(=O)O)cc1)c1csc(-c2cccs2)n1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 9
Group description: Razuprotafib Subcutaneous Solution: Up to 3 daily dose levels of Razuprotafib Subcutaneous Solution will be evaluated. Doses will be administered subcutaneously three times daily (Q8H) for 7 days.
Eligibility criteria:
Inclusion Criteria:

Ability to understand and provide informed consent;
Males and non-pregnant females 18 years of age or older at the time of Screening;
Laboratory-confirmed active SARS-CoV-2 infection within 72 hours prior to randomization, or (if testing results cannot be obtained) by evidence of progressive disease suggestive of ongoing SARS-CoV-2 infection;
Females of childbearing potential must be willing to completely abstain or agree to use a highly effective method of contraception through Day 28; and have a negative urine pregnancy test during Screening;
Currently hospitalized, receiving standard of care therapy for COVID-19, and meets the criteria for moderate or severe COVID-19, as follows: Moderate = symptoms of moderate illness with COVID-19, which could include any symptom of mild illness or shortness of breath with exertion and with respiratory rate at 20 or greater breaths/min, Peripheral capillary oxygen saturation (SpO2) >93% on room air at sea level, or heart rate at 90 or greater beats/min; Severe = symptoms suggestive of severe systemic illness with COVID-19, which could include any symptom of moderate illness, shortness of breath at rest, or respiratory distress, and respiratory rate at 30 or greater breaths/min, heart rate at 125 or greater beats/min, or SpO2 >93% on room air at sea level or (partial pressure of oxygen:fraction of inspired oxygen (PaO2:FiO2) <300.

Exclusion Criteria:

Inability to initiate study drug within 12 hours after randomization;
Female of childbearing potential who is unable or unwilling to forego breastfeeding through Day 28;
Systolic blood pressure <100 mmHg;
In shock or requiring pressor support;
Respiratory failure, defined as subjects who are on mechanical ventilation; are receiving oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20 L/min with fraction of delivered oxygen of 0.5 or greater), noninvasive positive pressure ventilation, or extracorporeal membrane oxygenation (ECMO); or have a clinical diagnosis of respiratory failure (ie, clinical need for 1 of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation);
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × the upper limit of normal (ULN);
Total bilirubin >2 × ULN;
Estimated glomerular filtration rate <30 mL/min or receiving hemodialysis or hemofiltration;
Moribund subject not expected to survive 24 hours in the opinion of the treating clinical team;
Any concurrent serious medical condition (eg, active malignancies on chemotherapy, post organ transplant, end stage congestive heart failure) or not likely to respond to treatment;
Decision to withhold life-sustaining treatment; Note: In the event of cardiac arrest, the decision to withhold cardiopulmonary resuscitation only does not fulfill this exclusion criterion.
Use of cytochrome P450 (CYP) 2 subfamily C, polypeptide 8 (2C8) substrates (eg, repaglinide, paclitaxel, or cerivastatin) or CYP3A4 substrates (eg, amlodipine, budesonide, dasabuvir, enzalutamide, imatinib, lopinavir, loperamide, saquinavir, sildenafil, midazolam, or montelukast);
Use of CYP2C8 inhibitors (eg, gemfibrozil, fluvoxamine, or ketoconazole);
Participation in another investigational study during the present study through the last visit (Day 28); or
Previous randomization in this study.