Trial Outcomes & Findings for Covid-19 Infection and Pulmonary Distress Treatment With Zanubrutinib in Hospitalized Participants (NCT NCT04382586)

Last Updated: 2024-10-26

Results Overview

Number of participants with respiratory failure-free survival, defined as not having died or gone into respiratory failure on or before Day 28

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

63 participants

Primary outcome timeframe

Up to Day 28

Results posted on

2024-10-26

Participant Flow

A total of 63 participants were randomized to receive zanubrutinib or placebo; four were randomized to the placebo group, but did not receive placebo treatment due to death (1 participant) and investigator decision (3 participants).

Participant milestones

Participant milestones
Measure	Zanubrutinib + Supportive Care Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Overall Study STARTED	30	33
Overall Study COMPLETED	13	17
Overall Study NOT COMPLETED	17	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Zanubrutinib + Supportive Care Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Overall Study Death	3	4
Overall Study Lost to Follow-up	11	8
Overall Study Withdrawal by Subject	3	1
Overall Study Physician Decision	0	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zanubrutinib + Supportive Care n=30 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=33 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Total n=63 Participants Total of all reporting groups
Age, Continuous	56.0 Years STANDARD_DEVIATION 12.51 • n=5 Participants	56.0 Years STANDARD_DEVIATION 13.30 • n=7 Participants	56.0 Years STANDARD_DEVIATION 12.83 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants	16 Participants n=7 Participants	32 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	17 Participants n=7 Participants	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	13 Participants n=5 Participants	6 Participants n=7 Participants	19 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	16 Participants n=5 Participants	26 Participants n=7 Participants	42 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Race/Ethnicity, Customized White	19 Participants n=5 Participants	25 Participants n=7 Participants	44 Participants n=5 Participants
Race/Ethnicity, Customized Other	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	3 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Day 28

Population: The Intent-to-Treat (ITT) Analysis Set includes all randomized participants

Number of participants with respiratory failure-free survival, defined as not having died or gone into respiratory failure on or before Day 28

Outcome measures

Outcome measures
Measure	Zanubrutinib + Supportive Care n=30 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=33 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Number of Participants With Respiratory Failure-free Survival	27 Participants	28 Participants

PRIMARY outcome

Timeframe: Up to 7 months

Population: The Intent-to-Treat (ITT) Analysis Set includes all randomized participants

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.

Outcome measures

Outcome measures
Measure	Zanubrutinib + Supportive Care n=30 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=33 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Time to Breathing Room Air	0.060 Events / total follow-up in days	0.061 Events / total follow-up in days

SECONDARY outcome

Timeframe: Up to Day 28

Population: The Intent-to-Treat (ITT) Analysis Set includes all randomized participants

Number of participants experiencing respiratory failure or death on or before Day 28

Outcome measures

Outcome measures
Measure	Zanubrutinib + Supportive Care n=30 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=33 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Number of Participants Experiencing Respiratory Failure or Death	3 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to Day 28

Population: The Intent-to-Treat (ITT) Analysis Set includes all randomized participants

Number of participants with all-cause mortality on or before Day 28

Outcome measures

Outcome measures
Measure	Zanubrutinib + Supportive Care n=30 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=33 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Number of Participants With All-cause Mortality	2 Participants	4 Participants

SECONDARY outcome

Timeframe: Up to Day 28

Population: The Intent-to-Treat (ITT) Analysis Set includes all randomized participants

Number of participants discharged alive on or before Day 28

Outcome measures

Outcome measures
Measure	Zanubrutinib + Supportive Care n=30 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=33 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Number of Participants Discharged Alive	26 Participants	28 Participants

SECONDARY outcome

Timeframe: Up to Day 28

Population: The Intent-to-Treat (ITT) Analysis Set includes all randomized participants; Here, overall number of participants analyzed represents participants who were admitted to the ICU and are evaluable for this outcome measure

Number of participants discharged alive from the intensive care unit (ICU) on or before Day 28

Outcome measures

Outcome measures
Measure	Zanubrutinib + Supportive Care n=14 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=13 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Number of Participants Discharged Alive From the ICU	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to Day 28

Population: The Intent-to-Treat (ITT) Analysis Set includes all randomized participants

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.

Outcome measures

Outcome measures
Measure	Zanubrutinib + Supportive Care n=30 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=33 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Number of Participants With Improvement in the World Health Organization (WHO) 8-point Ordinal Scale	22 Participants	25 Participants

SECONDARY outcome

Timeframe: Up to Day 28

Population: The Intent-to-Treat (ITT) Analysis Set includes all randomized participants, excluding participants who died before event completion; Here, overall number of participants analyzed represents participants who progressed from supplemental oxygen to mechanical ventilation and are evaluable for this outcome measure

Number of days on mechanical ventilation on or before Day 28

Outcome measures

Outcome measures
Measure	Zanubrutinib + Supportive Care n=3 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=4 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Duration of Mechanical Ventilation	4.0 Days Interval 3.0 to 24.0	13.5 Days Interval 3.0 to 26.0

SECONDARY outcome

Timeframe: Up to Day 28

Population: The Intent-to-Treat (ITT) Analysis Set includes all randomized participants, excluding participants who died before event completion

Number of days hospitalized on or before Day 28

Outcome measures

Outcome measures
Measure	Zanubrutinib + Supportive Care n=30 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=33 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Duration of Hospitalization	6.5 Days Interval 3.0 to 28.0	5.0 Days Interval 1.0 to 28.0

SECONDARY outcome

Timeframe: Baseline, Day 7, Day 14, Day 21 and Day 28

Population: The Intent-to-Treat Analysis Set included all randomized participants; Here, overall number of participants analyzed represents participants who progressed from supplemental oxygen to mechanical ventilation and are evaluable for this outcome measure and number analyzed represents participants with evaluable data at each time point

Partial pressure of oxygen (PaO2):fraction of inspired oxygen (FiO2) ratio

Outcome measures

Outcome measures
Measure	Zanubrutinib + Supportive Care n=3 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=3 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
PaO2:FiO2 Ratio Day 14	32.00 mmHg Interval 32.0 to 32.0	90.60 mmHg Interval 90.6 to 90.6
PaO2:FiO2 Ratio Baseline	—	53.0 mmHg Interval 53.0 to 53.0
PaO2:FiO2 Ratio Day 7	82.00 mmHg Interval 75.0 to 89.0	54.00 mmHg Interval 52.8 to 84.3
PaO2:FiO2 Ratio Day 21	—	52.10 mmHg Interval 52.1 to 52.1

SECONDARY outcome

Timeframe: Up to 7 months

Population: The Safety Analysis Set includes all participants who received any dose of study drug

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

Outcome measures

Outcome measures
Measure	Zanubrutinib + Supportive Care n=30 Participants Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=29 Participants Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Number of Participants With Adverse Events At least one TEAE	19 Participants	20 Participants
Number of Participants With Adverse Events Grade 3 or higher	6 Participants	6 Participants
Number of Participants With Adverse Events Serious adverse event	4 Participants	7 Participants
Number of Participants With Adverse Events Treatment-related TEAE	2 Participants	1 Participants

Adverse Events

Zanubrutinib + Supportive Care

Serious events: 4 serious events

Other events: 19 other events

Deaths: 3 deaths

Placebo + Supportive Care

Serious events: 7 serious events

Other events: 20 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Study Director

BeiGene

Phone: +1-877-828-5568

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee BeiGene has 18 months from the end of the study at all sites to publish overall study results. After the 1st multi-site publication or the expiration of publication period, Investigators are free to publish/present the results of the study. Investigators must submit all draft publications/presentations to us for review 60 days prior to the planned publication/presentation date. BeiGene may request deletion of its confidential information \& may request a further delay to protect its IP rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	Zanubrutinib + Supportive Care n=30 participants at risk Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo + Supportive Care n=29 participants at risk Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Blood and lymphatic system disorders Anaemia	0.00% 0/30 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	3.4% 1/29 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Cardiac disorders Right ventricular failure	0.00% 0/30 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	3.4% 1/29 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Infections and infestations COVID-19 pneumonia	3.3% 1/30 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	0.00% 0/29 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Infections and infestations Septic shock	0.00% 0/30 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	0.00% 0/29 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/30 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	0.00% 0/29 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Nervous system disorders Haemorrhage intracranial	0.00% 0/30 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	0.00% 0/29 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Nervous system disorders Ischaemic stroke	0.00% 0/30 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	3.4% 1/29 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Renal and urinary disorders Acute kidney injury	3.3% 1/30 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	3.4% 1/29 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	0.00% 0/30 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	0.00% 0/29 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/30 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	3.4% 1/29 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Respiratory, thoracic and mediastinal disorders Hypoxia	3.3% 1/30 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	6.9% 2/29 • Number of events 2 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	3.3% 1/30 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	3.4% 1/29 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/30 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	3.4% 1/29 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Respiratory, thoracic and mediastinal disorders Respiratory failure	6.7% 2/30 • Number of events 2 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	6.9% 2/29 • Number of events 2 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.
Vascular disorders Distributive shock	3.3% 1/30 • Number of events 1 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.	0.00% 0/29 • Up to 7 months Serious and other (not including serious) adverse events are reported for the Safety Analysis Set, which includes all participants who received any dose of study drug. All-cause mortality is reported for all randomized participants.