Evaluating Safety, Pharmacokinetics and Clinical Benefit of Silmitasertib (CX-4945) in Subjects With Moderate COVID-19

Inclusion Criteria

• Male or non-pregnant female adult ≥ 18 years of age
• Diagnosed with COVID-19 by standard RT-PCR assay or equivalent testing
• Outpatient subjects with moderate illness caused by SARS-CoV-2 infection as defined below,
• Symptoms of moderate systemic illness/infection with COVID-19:

At least two of the key COVID-19-related symptoms with score 2 or higher (0=none, 1=mild, 2=moderate, and 3=severe): cough, sore throat, malaise, headache, muscle pain, fever, neurological symptoms such as brain fog/concentration challenges, gastrointestinal symptoms or shortness of breath with exertion

AND

• Clinical signs indicative of moderate systemic illness/infection with COVID-19 At least 1 of the following: respiratory rate ≥ 20 breaths per minute, heart rate ≥ 90 beats per minute

AND

• No clinical signs indicative of Severe or Critical Illness Severity required hospitalization (see exclusion criterion #1)
• Patient (or legally authorized representative) provides written informed consent prior to initiation of any study procedures.
• Adequate hematopoietic capacity, as defined by the following:
• Hemoglobin ≥ 9.0 g/dL and not transfusion dependent
• Platelets ≥ 100,000/mm3
• Absolute neutrophil count ≥ 1500 cells/mm3
• Adequate hepatic function, as defined by the following:
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN
• Albumin ≥ 3.0 g/dL
• Adequate renal function, as defined by the following:

a. Renal: calculated creatinine clearance >45 mL/min for patients with abnormal, increased creatinine levels (Cockcroft-Gault formula).

• Ability to take oral medication and be willing to adhere to drug administration and premedication requirements (see Section 6.3) throughout study duration.

Exclusion Criteria

• Any signs indicative of Severe or Critical Illness Severity required hospitalization as defined below:
• Severe COVID-19: Shortness of breath in rest, or respiratory distress, respiratory rate (RR) >/= 30 per minute, heart rate (HR) >/=125 bpm, SpO2</=93% on room air at sea level or PaO2/FiO2<300
• Critical COVID-19: respiratory failure required mechanical ventilation, oxygen delivered by high-flow nasal cannula, ESMO; shock or multi-organ dysfunction/failure
• Pregnant or nursing women. (NOTE: Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a man father a child, or a woman become pregnant or suspect she is pregnant while participating in this study, he or she should inform the treating physician immediately.)
• Active or uncontrolled infections other than COVID-19 or with serious illnesses or medical conditions which would not permit the patient to receive study treatment
• Chronic diarrhea (excess of 2-3 stools/day above normal frequency)
• Concomitant treatment with another investigational drug from Day 1 through Day 28.
• Current use or anticipated need for drugs that are known strong inhibitors or inducers of major CYP enzymes.