Study of Oral Ibrutinib Capsules to Assess Respiratory Failure in Adult Participants With Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and Pulmonary Injury
Condition: CoronaVirus Induced Disease-2019 (COVID-19)
MeSH terms: COVID-19; Coronavirus Infections; Severe Acute Respiratory Syndrome; Respiratory Insufficiency; Lung Injury
Intervention: Ibrutinib; Placebo
Intervention description: Capsules were to be administered orally with water once daily. For participants who required nasogastric tube (NGT) placement while on study, capsules may have been administered by opening the capsules, mixing with water, and flushing down the NGT.; Capsules were to be administered orally with water once daily. For participants who required nasogastric tube (NGT) placement while on study, capsules may have been administered by opening the capsules, mixing with water, and flushing down the NGT.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 46.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: CoronaVirus Induced Disease-2019; COVID-19; Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2); Pulmonary Injury; Ibrutinib; Imbruvica; Respiratory failure

Summary:

      Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute
      respiratory syndrome coronavirus 2 (SARS-CoV-2). Lung failure is the main cause of death
      related to COVID-19 infection. The main objective of this study was to evaluate if ibrutinib
      is safe and can reduce respiratory failure in participants with COVID-19 infection.
    

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