Intervention: Ibrutinib
Trial phase: Phase 2
ATC code: L01EL01 | L01XE27
SMILES: C=CC(=O)N1CCC[C@@H](n2nc(-c3ccc(Oc4ccccc4)cc3)c3c(N)ncnc32)C1
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 22
Group description: 420 mg ibrutinib administered once daily as three hard gelatin capsules (140 mg each) with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)
Eligibility criteria:
Inclusion Criteria:

Requires hospitalization for COVID-19 infection
Has Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by reverse transcription polymerase chain reaction (RT-PCR) test before study entry
Requires supplemental oxygen for pulmonary distress related to COVID-19 infection, and has been on supplemental oxygen for no more than 5 days, and on breathing room air have oxygen saturation levels of 94% or less
Has radiographic evidence of pulmonary infiltrates
Females of childbearing potential (FCBP) must use 1 reliable form of contraception or have complete abstinence from heterosexual intercourse during the following time periods related to this study: while participating in the study; and for at least 1 month after discontinuation of study drug. FCBP must be referred to a qualified provider of contraceptive methods if needed. FCBP must have a negative serum pregnancy test as of screening.
Men must agree to use a latex condom during treatment and for up to 3 months after the last dose of ibrutinib during sexual contact with a FCBP.
Adequate hematologic, hepatic and renal function as described in the protocol
Must be within 10 days of confirmed diagnosis of COVID-19

Exclusion Criteria:

Respiratory failure at time of screening as defined per protocol with any of these following therapies:

Endotracheal intubation and mechanical ventilation
Extracorporeal membrane oxygenation (ECMO)
High flow nasal cannula oxygen at flow rates ≥ 30 L/min and fraction of delivered oxygen ≥ 0.5
Non-invasive positive pressure ventilation
Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction
On a Bruton's tyrosine kinase (BTK)-inhibitor, anti-interleukin 6 (IL6), anti-interleukin 6R (IL6R), or Janus kinase inhibitor (JAKi)
Has received rituximab within 180 days from study entry.
Known bleeding disorders
Major surgery within 4 weeks of study entry
Participants in whom surgery is anticipated to be necessary within 72 hours
History of stroke or bleeding around or within brain within 6 months prior to enrollment
Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV)
Currently active, clinically significant cardiovascular disease
Asymptomatic arrythmias and or history of ejection fraction < 40% on an echo
Participants receiving a strong cytochrome P450 (CYP) 3A4 inhibitor with the exception of those receiving anti-fungal therapy/prophylaxis
Chronic liver disease and hepatic impairment meeting Child Pugh class C
Female participants who are pregnant, or breastfeeding, or planning to become pregnant while enrolled in this study or within 1 month of last dose of study drug. Male participants who plan to father a child while enrolled in this study or within 3 months after the last dose of study drug.
Unwilling or unable to participate in all required study evaluations and procedures
Vaccinated with a live, attenuated vaccine within 4 weeks
Uncontrolled high blood pressure
On therapeutic anticoagulation at baseline
Participants with cancer, history of interstitial lung disease, and/or history of malignancies as defined in the protocol
Co-enrolled in another interventional trial
Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≥ 3.0 × ULN, and total bilirubin > 2.0 × ULN
International normalized ratio (INR) ≥ 1.5 × ULN attributable to coagulation disorders