Acalabrutinib Study With Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized With COVID-19.

Percent Change From Baseline in Absolute Lymphocyte Count

Baseline is defined as the result obtained on the date of randomization. If no result was obtained on the date of randomization, the last result prior to the date of randomization is used. Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value. The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.

Time frame: Days 3, 5, 7, 10, 14, 28

Overall Survival

Median overall survival, calculated using the Kaplan-Meier technique. Confidence interval for median overall survival (days) is derived based on Brookmeyer-Crowley method with log-log transformation.

Time frame: From randomization until 90 days after randomization. Safety Issue:

Percentage of Participants Alive and Discharged From ICU

Time frame: At Day 14 and at Day 28

Time From Randomization to First Occurrence of Respiratory Failure or Death on Study Due to Any Cause

Median time to first occurrence of respiratory failure or death, calculated using the Kaplan-Meier technique. Confidence interval for median overall survival (days) is derived based on Brookmeyer-Crowley method with log-log transformation.

Time frame: From randomization to 28 days after randomization.

Number of Days Alive and Free of Respiratory Failure

Respiratory failure, is defined based on resource utilization of any of the following modalities: a) Endotracheal intubation and mechanical ventilation b) Oxygen delivered by highflow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20 L/min with fraction of delivered oxygen ≥0.5) c) Non-invasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation

Time frame: From randomization to 28 days after randomization.

Number of Days With Respiratory Failure

Respiratory failure, is defined based on resource utilization of any of the following modalities: a) Endotracheal intubation and mechanical ventilation b) 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 ≥0.5) c) Non-invasive positive pressure ventilation or continuous positive airway pressure d) Extracorporeal membrane oxygenation For participants who die (due to any cause) prior to Day 28, days from death to Day 28 are counted as days with respiratory failure. For participants in hospital and experiencing respiratory failure at the time they withdraw from the study, days from last known status to Day 28 are counted as days with respiratory failure.

Time frame: From randomization to 28 days after randomization.

Number of Days Hospitalized

For this summary, the hospitalization must be considered clinically indicated to count as a day hospitalized. For participants who die (due to any cause) prior to Day 28, days from death to Day 28 are counted as days hospitalized. For participants in hospital at the time they withdraw from the study, days from last known status to Day 28 are counted as days hospitalized.

Time frame: From randomization to 28 days after randomization.

Number of Days in ICU

For this summary, the ICU stay must be considered clinically indicated to count as a day in ICU. For participants who die (due to any cause) prior to Day 90, days from death to Day 90 are counted as days in ICU.

Time frame: From randomization to 90 days after randomization.

Number of Days Alive Outside of Hospital

Time frame: From randomization to 28 days after randomization.

Number of Days Alive Outside of Hospital

Time frame: From randomization to 90 days after randomization.

Percent Change From Baseline in Oxygenation Index

Baseline is defined as the result obtained on the date of randomization. Percent change from baseline at Day X is calculated by multiplying the following result by 100%: (Day X value - Baseline value)/Baseline value. The mean of this result for all analyzed patients is taken to get the mean percent change from baseline.

Time frame: Days 3, 5, 7, 10, 14, 28

Time From Randomization to Clinical Improvement of at Least 2 Points on a 9-point Category Ordinal Scale

9-point category ordinal scale: 0. \* Uninfected, no clinical or virological evidence of infection 1. Ambulatory, no limitation of activities 2. Ambulatory, limitation of activities 3. Hospitalized - mild disease, no oxygen therapy 4. Hospitalized - mild disease, oxygen by mask or nasal prongs 5. Hospitalized - severe disease, non-invasive ventilation or high flow oxygen 6. Hospitalised - severe disease, intubation and mechanical ventilation 7. Hospitalized - severe disease, ventilation and additional organ support, such as pressors, renal replacement therapy, extracorporeal membrane oxygenation 8. Death Median time to first occurrence of respiratory failure or death, calculated using the Kaplan-Meier technique. Confidence interval for median overall survival (days) is derived based on Brookmeyer-Crowley method with log-log transformation.

Time frame: From randomization to 28 days after randomization.

Pharmacokinetics of Acalabrutinib

Summary of plasma concentrations (ng/mL) of acalabrutinib

Time frame: Day 3 and Day 7

Pharmacokinetics of ACP-5862

Summary of plasma concentrations (ng/mL) of ACP-5862

Time frame: Day 3 and Day 7