Covid-19 Infection and Pulmonary Distress Treatment With Zanubrutinib in Hospitalized Participants

A Phase 2, Randomized, Double Blind, Placebo-Controlled Study of Zanubrutinib Treatment in Patients Hospitalized for COVID-19 Infection and Pulmonary Distress

The primary objective of this study was to evaluate if the addition of zanubrutinib to supportive care increases the respiratory failure-free survival rate at Day 28 in participants hospitalized for Corona Virus Disease 2019 (COVID-19) and pulmonary distress not receiving mechanical ventilation.

Study Overview

• Status: Completed
• Conditions: COVID-19; COVID-19 Pulmonary Complications
• Intervention / Treatment: Drug: Placebo; Drug: Zanubrutinib; Drug: Supportive Care

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Fullerton, California, United States, 92835
      • St Jude Medical Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Medstar Heath Research Institute Medstar Washington Hospital Center
  • Georgia
    • Thomasville, Georgia, United States, 31792
      • John D Archbold Memorial Hospital
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • The Brigham and Womens Hospital, Inc
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers University Hospital
  • Texas
    • Houston, Texas, United States, 77004
      • Therapeutics Concepts
    • Lubbock, Texas, United States, 79410
      • Joe Arrington Cancer Research and Treatment Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Hospitalization for COVID-19 infection
2. Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection confirmed by polymerase chain reaction (PCR)
3. Participant requires supplemental oxygen for pulmonary distress related to COVID-19 infection, and has been on supplemental oxygen for no more than 96 hours from time of screening

Key Exclusion Criteria:

1. 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
2. On a Bruton's tyrosine kinase (BTK) inhibitor
3. Planned or concurrent use of a host modifiers/immune-based therapies or anti-CD20 monoclonal antibody treatment
4. Participants with prior of current hematologic malignancy or solid tumor malignancy with treatment within 6 months prior to study entry

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Zanubrutinib + Supportive Care; Participants received zanubrutinib plus supportive care	Drug: Zanubrutinib; 320 mg (4 x 80 mg) capsules administered orally once daily; Other Names: Brukinsa; BGB-3111; Drug: Supportive Care; Supportive care treatment was selected and administered as deemed appropriate by the study investigator
Active Comparator: Placebo + Supportive Care; Participants received placebo plus supportive care alone	Drug: Placebo; Placebo to match zanubrutinib; Drug: Supportive Care; Supportive care treatment was selected and administered as deemed appropriate by the study investigator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Respiratory Failure-free Survival	Number of participants with respiratory failure-free survival, defined as not having died or gone into respiratory failure on or before Day 28	Up to Day 28
Time to Breathing Room Air	Time to return to breathing room air is defined as the time from randomization date to the earliest time where the participant is stable on room air without supplemental oxygen. Total follow-up time in days is the total time of all participants from the randomization date to the first event date or Day 28 if there is no event. The rate was calculated as total number of events in which a participant returned to breathing room air on or before Day 28 divided by the total follow-up time in days.	Up to 7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Experiencing Respiratory Failure or Death	Number of participants experiencing respiratory failure or death on or before Day 28	Up to Day 28
Number of Participants With All-cause Mortality	Number of participants with all-cause mortality on or before Day 28	Up to Day 28
Number of Participants Discharged Alive	Number of participants discharged alive on or before Day 28	Up to Day 28
Number of Participants Discharged Alive From the ICU	Number of participants discharged alive from the intensive care unit (ICU) on or before Day 28	Up to Day 28
Number of Participants With Improvement in the World Health Organization (WHO) 8-point Ordinal Scale	Number of participants with improvement in WHO 8-point-scale, in which improvement was considered a score that changed from ≥4 at baseline to ≤ 3 at Day 28 as assessed by the investigator. Scoring ranges from 0 = uninfected with no clinical or virologic evidence of disease to 8 = dead.	Up to Day 28
Duration of Mechanical Ventilation	Number of days on mechanical ventilation on or before Day 28	Up to Day 28
Duration of Hospitalization	Number of days hospitalized on or before Day 28	Up to Day 28
PaO2:FiO2 Ratio	Partial pressure of oxygen (PaO2):fraction of inspired oxygen (FiO2) ratio	Baseline, Day 7, Day 14, Day 21 and Day 28
Number of Participants With Adverse Events	Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), treatment-related adverse events (AEs), and TEAEs grade 3 or higher, including laboratory findings	Up to 7 months

Collaborators and Investigators

• Sponsor: BeiGene
• Investigators: Principal Investigator: Study Director, BeiGene

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2020
• Primary Completion (Actual): February 1, 2021
• Study Completion (Actual): February 1, 2021

Study Registration Dates

• First Submitted: May 7, 2020
• First Submitted That Met QC Criteria: May 7, 2020
• First Posted (Actual): May 11, 2020

Study Record Updates

• Last Update Posted (Actual): October 26, 2024
• Last Update Submitted That Met QC Criteria: October 23, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; Corona Virus
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Zanubrutinib
• Other Study ID Numbers: BGB-3111-219

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No