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

Full analysis set (as randomized).

Safety analysis set: If the participant receives at least 1 dose of acalabrutinib, they are summarized in the Acalabrutinib + BSC group. Otherwise, they are summarized in the BSC alone group.

The number of participants in the BSC alone group (91) is greater than the number of participants randomized to this group (88) because three participants randomized to Acalabrutinib + BSC did not receive any acalabrutinib and therefore are included in the BSC alone group for the safety analysis set.

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

Full analysis set (as randomized).

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.

Full analysis set (as randomized).

Participants require a baseline and post-baseline result at the given timepoint to be included in the number analyzed for that timepoint.

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.

Full analysis set (as randomized).

Participants require a baseline and post-baseline result at the given timepoint to be included in the number analyzed for that timepoint.

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.

Full analysis set (as randomized).

Participants require a baseline and post-baseline result at the given timepoint to be included in the number analyzed for that timepoint.

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.

Full analysis set (as randomized).

Full analysis set (as randomized).

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.

Full analysis set (as randomized).

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

Full analysis set (as randomized).

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.

Full analysis set (as randomized).

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.

Full analysis set (as randomized).

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.

Full analysis set (as randomized).

Full analysis set (as randomized).

Full analysis set (as randomized).

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.

Full analysis set (as randomized).

Participants require a baseline and post-baseline result at the given timepoint to be included in the number analyzed for that timepoint.

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.

Full analysis set (as randomized).

Participants require a baseline and at least one post-baseline result to be included in the number analyzed.

Summary of plasma concentrations (ng/mL) of acalabrutinib

PK analysis set: all participants who received at least 1 dose of acalabrutinib and had at least 1 post-dose evaluable pharmacokinetic (PK) data point for acalabrutinib or ACP-5862.

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

PK analysis set: all participants who received at least 1 dose of acalabrutinib and had at least 1 post-dose evaluable pharmacokinetic (PK) data point for acalabrutinib or ACP-5862.