A Phase 2, Open-Label, Randomized Study of the Efficacy and Safety of Acalabrutinib with Best Supportive Care Versus Best Supportive Care in Subjects Hospitalized with COVID-19

INTERVENTION: Product Name: acalabrutinib Product Code: ACP‐196 Pharmaceutical Form: Capsule, hard INN or Proposed INN: ACALABRUTINIB CAS Number: 1420477‐60‐6 Current Sponsor code: ACP‐196 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 100‐ CONDITION: Subjects with life‐threatening COVID‐19 symptoms Therapeutic area: Diseases [C] ‐ Virus Diseases [C02] PRIMARY OUTCOME: Main Objective: The overall objective of the study is to evaluate the efficacy of adding acalabrutinib to BSC for the treatment of COVID‐19 Primary end point(s): Primary Endpoint is Proportion of subjects alive and free of; respiratory failure at Day 14.; ; For the purpose of this study, 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 >20L/min with fraction of delivered oxygen =0.5); (c) Noninvasive positive pressure ventilation or continuous positive airway pressure; (d) Extracorporeal membrane oxygenation Secondary Objective: To assess pharmacokinetics of acalabrutinib and its active metabolite in subjects with COVID‐19 when administered with BSC; ; To evaluate the safety of acalabrutinib in; subjects with COVID‐19 when; administered with BSC Timepoint(s) of evaluation of this end point: 14 days; SECONDARY OUTCOME: Secondary end point(s): Proportion of subjects alive and free of respiratory failure (as defined above) at Day 28 ; Percent change from baseline in CRP (time frame: baseline, Days 3, 5, 7, 10, 14, 28) ; Change from baseline in ferritin (time frame: baseline, Days 3, 5, 7, 10, 14, 28) ; Change from baseline in absolute lymphocyte counts (time frame: baseline, Days 3, 5, 7, 10, 14, 28) ; All‐cause mortality at Day 90 ; Proportion of subjects alive and discharged from the ICU at Days 14 and 28 ; Time from randomization to first occurrence of respiratory failure or death on study (up to 28 days after randomization) due to any cause ; Number of days alive and free of respiratory failure from randomization to 28 days after randomization ; Number of days with respiratory failure from randomization to 28 days after randomization ; Number of days hospitalized from randomization to 28 days after randomization ; Number of days in ICU (length of stay) from randomization to 90 days after randomization ; Number of days alive outside of hospital from randomization to 28 days after randomization ; Number of days alive outside of hospital from randomization to 90 days after randomization ; Relative change from baseline in oxygenation index (SpO2/FiO2) to Days 3, 5 , 7 and 10 ; Type, frequency, severity, and relationship to study treatment of any TEAEs or abnormalities of laboratory tests, SAEs, or AEs leading to discontinuation of study treatment ; Time to clinical improvement of at least 2 points (from randomization) on a 9‐point category ordinal scale through Day 28 ; Time to SpO2 > 94% on room air ; Summarized plasma concentrations of acalabrutinib and ACP‐5862 at specified time points. Pharmacokinetic parameters (eg, AUC and Cmax) estimated, as appropriate Timepoint(s) of evaluation of this end point: approximately 28 days and for survival status approximately 90 days INCLUSION CRITERIA: 1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent 2. Men and women =18 years of age at the time of signing the informed consent form 4. COVID‐19 pneumonia (documented radiographically) requiring hospitalization and oxygen saturation <94% on room air or requires supplemental oxygen 3. SARSCoV2 confirmed per World Health Organization (WHO) criteria (including positive nucleic acid test of any specimen [eg, respiratory, blood, urine, stool, or other bodily fluid]) within 7 days of randomization 5. Able to swallow pills 6. Willing to follow contraception guidelines Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 40