Phase 2
N=46
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
CoronaVirus Induced Disease-2019 (COVID-19)
Bottom Line
View on ClinicalTrials.gov: NCT04375397 ↗Enrolled (actual)
46
Serious AEs
15.2%
Results posted
Jun 2022
Primary outcome: Primary: Percentage of Participants Alive and Without Respiratory Failure Through Day 28 — 86.4; 79.2 percentage of participants — p==0.599
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Ibrutinib (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AbbVie
- Primary completion
- May 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Alive and Without Respiratory Failure Through Day 28 |
86.4; 79.2 | =0.599 |
| SECONDARY Change in the World Health Organization (WHO)-8 Ordinal Scale From Baseline at Study Day 14 |
2; 3; 12; 9; 5; 7 | =0.886 |
| SECONDARY Median Reduction in Days Spent on Supplemental Oxygen |
5.0; 6.5 | =0.801 |
| SECONDARY All-Cause Mortality at Study Days 7, 14, 21, and 28 |
0; 0; 0; 0; 4.5; 0 | =1.000 |
| SECONDARY Percentage of Participants Experiencing Respiratory Failure or Death on Study Days 7, 14, 21, and 28 |
9.1; 20.8; 9.1; 20.8; 13.6; 20.8 | =0.314 |
| SECONDARY Mechanical Ventilation-Free Survival |
NA; NA | =0.851 |
| SECONDARY Days on Mechanical Ventilation |
0.0; 0.0 | =0.745 |
| SECONDARY Median Duration of Hospitalization |
6.0; 6.5 | =0.977 |
| SECONDARY Time to Discharge From Hospital |
6.0; 6.5 | =0.969 |
| SECONDARY Partial Pressure of Oxygen in Arterial Blood (PaO2) to Fraction of Inspired Oxygen (FiO2) Ratio |
100; 87; 269 | — |
| SECONDARY Oxygenation Index |
14; 19; 12; 33; 20; 12 | — |
| SECONDARY Number of Participants With Adverse Events |
12; 12 | — |
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 2.0 × ULN
- International normalized ratio (INR) ≥ 1.5 × ULN attributable to coagulation disorders
Data sourced from ClinicalTrials.gov (NCT04375397). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.