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

NCT ID: NCT04375397

Last Updated: 2022-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-06-06
• Study Completion Date: 2021-06-08

Brief 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.

Detailed Description

This was a Phase 2, multicenter, randomized, placebo-controlled, double-blind study to evaluate the addition of ibrutinib to supportive care in hospitalized participants who presented with COVID-19- related pulmonary distress requiring supplemental oxygen. Participants were randomized in a 1:1 ratio to receive placebo + supportive care, denoted as SOC or standard-of-care, or ibrutinib 420 mg + SOC, with randomization stratified by prescription for remdesivir.

Participants were to be treated with either placebo or ibrutinib in addition to supportive care for up to 28 days unless they met treatment discontinuation criteria and were to be followed for 58 days following start of therapy or until death, whichever occurred first. Treatment could have been stopped at the discretion of the treating physician after 14 days if the participant was clinically stable and had been off supplemental oxygen for > 48 hours.

Conditions

CoronaVirus Induced Disease-2019 (COVID-19)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ibrutinib 420 mg + SOC

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)

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

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.

Placebo + SOC

Three hard gelatin placebo capsules administered once daily with approximately 240 mL of water for up to 28 days and supportive care (standard-of-care, SOC)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

Ibrutinib

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.

Intervention Type: DRUG

Placebo

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.

Intervention Type: DRUG

Other Intervention Names

Imbruvica

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development LLC; Pharmacyclics LLC (An AbbVie Company)

UNKNOWN

Sponsor Role: collaborator

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ABBVIE INC.

Role: STUDY_DIRECTOR

AbbVie

Locations

Stanford University School of Med /ID# 221954

Stanford, California, United States

Medstar Washington Hospital Center /ID# 221886

Washington D.C., District of Columbia, United States

Duplicate_GW Medical Faculty Associates /ID# 222023

Washington D.C., District of Columbia, United States

Midway Immunology and Research /ID# 222004

Ft. Pierce, Florida, United States

University of Miami /ID# 223227

Miami, Florida, United States

Triple O Research Institute /ID# 222944

West Palm Beach, Florida, United States

Brigham & Women's Hospital /ID# 221847

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center /ID# 222994

Boston, Massachusetts, United States

Intermountain Healthcare /ID# 221955

Salt Lake City, Utah, United States

Countries

United States

References

Coutre SE, Barnett C, Osiyemi O, Hoda D, Ramgopal M, Fort AC, Qaqish R, Hu Y, Ninomoto J, Alami NN, Styles L, Treon SP. Ibrutinib for Hospitalized Adults With Severe Coronavirus Disease 2019 Infection: Results of the Randomized, Double-Blind, Placebo-Controlled iNSPIRE Study. Open Forum Infect Dis. 2022 Mar 24;9(5):ofac104. doi: 10.1093/ofid/ofac104. eCollection 2022 May.

Reference Type: DERIVED

PMID: 35493119 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

M20-310

Identifier Type: -

Identifier Source: org_study_id