Primary Objective:

To evaluate the safety and tolerability of CX-4945 in adult COVID-19 patients hospitalized with positive SARS-CoV-2

• Safety variables include but are not limited to vital assessment, physical examinations, clinical laboratory assessments (hematology, biochemistry, coagulation, urinalysis, etc.), 12-lead electrocardiogram (ECG), chest X-ray (CXR), and adverse events (AEs) by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
• The proportion of subjects with treatment-emergent AEs (TEAEs) leading to study drug discontinuation.

Secondary Objectives:

To evaluate the efficacy of CX-4945 in adult COVID-19 patients hospitalized with positive SARS-CoV-2

• Baseline change in the World Health Organization (WHO) Ordinal Scale on Days 2, 3, 4, 5, 7, 14, 30 and discharge day when applicable.
• Time to COVID-19 clinical improvement on Days 2, 3, 4, 5, 7, 14, 30, and discharge day when applicable. Clinical improvement is defined as a positive baseline change in the WHO Ordinal Scale by 2 points or higher.
• Baseline change in the cycle threshold (Ct) values in SARS-CoV-2 reverse transcriptase-polymerase chain reaction (RT-PCR) testing on Days 3, 5, 14, 30, and discharge day when applicable.
• Time to SARS-CoV-2 clearance, defined by time from randomization to the first 2 consecutive negative RT-PCR test results (sampling interval ≥24 hours).
• Percentage of subjects requiring critical care unit admission within 30 days.
• Proportion of subjects alive and free of respiratory failure, determined by the Investigator, on Day 30.

Exploratory endpoints:

• Baseline change in ferritin, C-reactive protein (CRP), D-dimer, lactate dehydrogenase (LDH), neutrophil to lymphocyte ratio (NLR), neutrophil to CD4+ T lymphocyte ratio (N4R), neutrophil to CD3+ T lymphocyte ratio (N3R), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colony-stimulating factor (GM-CSF) on Days 3, 5, 7, 14 and 30.
• Baseline change in IL-1b, IL-2, IL-6, IL-7, IL-8, IL-10, IL-18, monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1) on Days 3, 5, 7, 14 and 30.

Primary Objective:

To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared to placebo plus SOC, in preventing the progression of CAP associated with SARS-CoV-2 and influenza virus infection

• The percentage of subjects requiring hospitalization, including emergency room visits, due to progression of CAP related to SARS-CoV-2 or influenza

Secondary Objectives:

To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared with placebo plus SOC, in enhancing the subject's clinical condition

 

• The percentage of subjects with all cause hospitalization during study period
• The percentage of subjects with improved pulmonary X-ray findings for pneumonia, relative to baseline or showing a return to normalcy
• Time to symptom resolution for fever
• Change from baseline in SpO2/FiO2 ratio ;
• The percentage of subjects exhibiting disease progression in health status (evaluated using the National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale/6-point ordinal scale)
• The percentage of subjects exhibiting disease improvement in health status (evaluated using the National Institute of Allergy and Infectious Diseases (NIAID) 8-point ordinal scale/6-point ordinal scale)
• To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared with placebo plus SOC, in reducing viral load.Change from baseline in viral load/Ct values in nasal secretions by qRT-PCR. (only for SARS-CoV-2 domain)
• Time to FilmArray confirmed resolution of viral infection
• To evaluate the safety and tolerability of Silmitasertib (CX-4945)TEAEs and SAEs

Exploratory Objective:

To evaluate the effect of intervention with Silmitasertib (CX-4945) in addition to SOC, compared with placebo plus SOC, on inflammatory status and on moderating the elevated cytokine release associated with SARS-CoV-2 and influenza virus infection

• The percentage of subjects achieving normalized CRP levels.
• Change from baseline in ferritin, C-reactive protein (CRP), CRP to albumin ratio (CAR), D-dimer, lactate dehydrogenase (LDH)...etc.
• Changes from baseline in serum cytokine levels: Cytokines to be quantified; IL-6, IL-1β, tumor necrosis factor alpha (TNF-α)...etc.