Health Condition 1: J960- Acute respiratory failure Health Condition 2: B972- Coronavirus as the cause of diseases classified elsewhere
Conditions
Interventions
Intervention1: Acalabrutininb (ACP-196): 1:1Assignment
Route of Administration: Oral.
Duration of therapy: 10 days
Frequency:Twice daily (BID)
Control Intervention1: Best Supportive Care: 1:1 Assign
Sponsors
Acerta Pharma BV
AstraZeneca Pharma India Ltd
Eligibility
Inclusion criteria
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 3. SARS-CoV-2 confirmed per World Health Organization (WHO) criteria within 4 days of randomization. 4. COVID-19 pneumonia (documented radiographically) requiring hospitalization and oxygen saturation 5. Able to swallow pills. 6. Willing to follow contraception guidelines
Exclusion criteria
Exclusion criteria: COVID-19 Related Medical Conditions 1. Respiratory failure at the time of screening due to COVID-19 pneumonia. 2. Known medical resuscitation within 14 days of randomization. 3. Any serious medical condition or abnormality of clinical laboratory tests that, in the Investigators judgment, precludes the subjects safe participation in and completion of the study 4. Suspected uncontrolled active bacterial, fungal, viral, or other infection (besides infection with SARSCoV2). 5. In the opinion of the Investigator, progression to death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments Medical Conditions 6. Not expected to survive 28 days given their pre-existing, uncorrectable medical condition. 7. Pregnant or breast feeding. 8. Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin >= 3x upper limit of normal (ULN) and/or severe hepatic impairment (Child-Pugh class C). 9. Absolute neutrophil count (ANC) 10. Platelet count 11. Estimated creatinine clearance of 12.Uncontrolled or untreated symptomatic arrhythmias, myocardial infarction within the last 6 weeks, or congestive heart failure (NYHA Grade 3 or 4). Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening area allowed to enrol on study. 13.History of chronic hypercarbia, respiratory failure in past 6 months, or use of home oxygen in the setting of severe chronic respiratory disease. 14.Quadriplegia. 15.History of primary immunodeficiency, tuberculosis, progressive multifocal leukoencephalopathy (PML), aspergillus or other invasive mold/fungal infection, or received organ or bone marrow transplantation within 6 months of randomization. 16.Known active hepatitis B or C infection requiring therapy. Prior/Concomitant Therapy: 17.Treatment with a strong cytochrome P450 (CYP)3A inhibitor (within 14 days before first dose of study drug) or inducer (within 7 days before first dose of study drug). 18.Requires treatment with proton-pump inhibitors. 19.Received oral antirejection or immunomodulatory drugs. 20.Active participation in other drug clinical trials or received treatment with an investigational drug within 5 half-lives or 30 days (whichever is longer) of randomization/enrolment. 21.Subjects at randomization who require inhaled corticosteroids or maintenance doses of more than 7.5 mg of prednisone or equivalent per day. 22.Requires or is receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of acalabrutinib. 23.History of hypersensitivity (ie, allergic response) to active or inactive excipients of acalabrutinib or other Btk inhibitors. 24.Known cytoreductive chemotherapy treatment within 14 days of randomization. 25.Major surgery (as defined by the Investigator) within 4 weeks prior to randomization or still recovering from prior surgery.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The overall objective of the study is to evaluate the efficacy of adding acalabrutinib to BSC for the treatment of COVID-19. 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 (c) Non-invasive positive pressure ventilation or continuous positive airway pressure (d) Extracorporeal membrane oxygenation Timepoint: Proportion of subjects alive and free of respiratory failure at Day 14 | — |
Secondary
| Measure | Time frame |
|---|---|
| Exploratory Endpoints/Variables: Change from baseline in cytokines/chemokines such as INFỾ, TNFα, IL-1β, IL-6, IL-8, IL-10, IL-18, MCP-1, etc Change from baseline in SARS-CoV-2 levels and serology Btk occupancy compared to pre-dose Correlative analysis with treatment effects to determine if any biomarkers can predict response, as well as any relationship to study drug exposure levels Timepoint: Entire duration of the trial;Exploratory Objectives: Evaluate changes in inflammatory cytokines/chemokines associated with COVID-19 SARS-CoV-2 and quantitative serology Pharmacodynamic effects of acalabrutinib Timepoint: Entire duration of the trial;PK Endpoint/Variable: Acalabrutinib, Cmax, tmax, t1/2, AUC 0-time, and its active metabolite, ACP-5862 Cmax, and other PK parameters (e.g. CL/F or Vdss/F) where appropriate Timepoint: Entire duration of the trial;PK objective: To assess PK of Acalabrutinib and its active metabolite in subjects with COVID-19 when administered with BSC Timepoint: Entire duration of the trial;Safety Endpoint/Variable: 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 Timepoint: Entire duration of the trial;Safety Objective: To evaluate the safety of acalabrutinib in subjects with COVID-19 when administered with BSC Timepoint: Entire duration of the trial;To evaluate the efficacy of adding acalabrutinib to BSC for the treatment of COVID-19. Percent change from baseline in CRPTimepoint: Time frame: baseline, Days 3, 5, 7, 10, 14, 28;To evaluate the efficacy of adding acalabrutinib to BSC for the treatment of COVID-19. Proportion of subjects alive and free of respiratory failureTimepoint: at Day 28;To evaluate the efficacy of adding acalabrutinib to BSC for the treatment of COVID-19 Change from baseline in absolute lymphocyte countsTimepoint: Time frame: baseline, Days 3, 5, 7, 10, | — |
Countries
Brazil, France, Germany, India, Italy, Japan, Russian Federation, Spain, Sweden, Turkey
Contacts
Public ContactTapankumar M Shah
AstraZeneca Pharma India Ltd
Outcome results
None listed