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

• Sponsor: BeiGene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04382586
• Collaborator: (none)
• Enrollment: 63
• Locations: 18
• Arms: 2
• Actual Duration (Months): 6.9
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Pulmonary Complications; COVID-19	Drug: Zanubrutinib; Drug: Supportive Care; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Randomized, Double Blind, Placebo-Controlled Study of Zanubrutinib Treatment in Patients Hospitalized for COVID-19 Infection and Pulmonary Distress
• Actual Study Start Date: Jul 6, 2020
• Actual Primary Completion Date: Feb 1, 2021
• Actual Study Completion Date: Feb 1, 2021

Arms and Interventions

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: BGB-3111 Brukinsa ; 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: Supportive Care; Supportive care treatment was selected and administered as deemed appropriate by the study investigator; Drug: Placebo; Placebo to match zanubrutinib

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Respiratory Failure-free Survival [Up to Day 28]

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

2. Time to Breathing Room Air [Up to 7 months]

   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.

Secondary Outcome Measures

1. Number of Participants Experiencing Respiratory Failure or Death [Up to Day 28]

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

2. Number of Participants With All-cause Mortality [Up to Day 28]

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

3. Number of Participants Discharged Alive [Up to Day 28]

   Number of participants discharged alive on or before Day 28

4. Number of Participants Discharged Alive From the ICU [Up to Day 28]

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

5. Number of Participants With Improvement in the World Health Organization (WHO) 8-point Ordinal Scale [Up to Day 28]

   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.

6. Duration of Mechanical Ventilation [Up to Day 28]

   Number of days on mechanical ventilation on or before Day 28

7. Duration of Hospitalization [Up to Day 28]

   Number of days hospitalized on or before Day 28

8. PaO2:FiO2 Ratio [Baseline, Day 7, Day 14, Day 21 and Day 28]

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

9. Number of Participants With Adverse Events [Up to 7 months]

   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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Honor Health	Scottsdale	Arizona	United States	85258
2	St. Jude Medical Center	Fullerton	California	United States	92835
3	Olive View - UCLA Medical Center	Sylmar	California	United States	91342
4	MedStar Heath Research Institute/ MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
5	Augusta University	Augusta	Georgia	United States	30912
6	John D. Archbold Memorial Hospital	Thomasville	Georgia	United States	31792
7	Loyola University Medical Center	Maywood	Illinois	United States	60153
8	SIU School of Medicine	Springfield	Illinois	United States	62629
9	University of Iowa	Iowa City	Iowa	United States	52242
10	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
11	Brigham And Women's Hospital	Boston	Massachusetts	United States	02115
12	Morristown Medical Center	Morristown	New Jersey	United States	07960
13	Rutgers University Hospital	Newark	New Jersey	United States	07103
14	Atlantic Health System, Inc. / Chilton Medical Center	Pompton Plains	New Jersey	United States	07444
15	Overlook Medical Center	Summit	New Jersey	United States	07901
16	Therapeutic Concepts	Houston	Texas	United States	77004
17	Covenant Health System	Lubbock	Texas	United States	79140
18	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• BeiGene

Investigators

• Principal Investigator: Study Director, BeiGene

Study Documents (Full-Text)

• Study Protocol - Jan 8, 2021
• Statistical Analysis Plan - Mar 3, 2021

More Information

Publications

None provided.

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT04382586
• Other Study ID Numbers: BGB-3111-219
• First Posted: May 11, 2020
• Last Update Posted: Mar 2, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• 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
• Keywords provided by BeiGene: Corona Virus; COVID-19
• Additional relevant MeSH terms: COVID-19; Zanubrutinib

Study Results

Participant Flow

Recruitment Details	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).

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Period Title: Overall Study
STARTED	30	33
COMPLETED	13	17
NOT COMPLETED	17	16

Baseline Characteristics

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care	Total
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Total of all reporting groups
Overall Participants	30	33	63
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56.0 (12.51)	56.0 (13.30)	56.0 (12.83)
Sex: Female, Male (Count of Participants)
Female	16 53.3%	16 48.5%	32 50.8%
Male	14 46.7%	17 51.5%	31 49.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	13 43.3%	6 18.2%	19 30.2%
Not Hispanic or Latino	16 53.3%	26 78.8%	42 66.7%
Unknown or Not Reported	1 3.3%	1 3%	2 3.2%
Race/Ethnicity, Customized (Count of Participants)
Asian	2 6.7%	2 6.1%	4 6.3%
Black or African American	3 10%	5 15.2%	8 12.7%
White	19 63.3%	25 75.8%	44 69.8%
Other	1 3.3%	1 3%	2 3.2%
Unknown	3 10%	0 0%	3 4.8%
Not Reported	2 6.7%	0 0%	2 3.2%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Respiratory Failure-free Survival
Description	Number of participants with respiratory failure-free survival, defined as not having died or gone into respiratory failure on or before Day 28
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Measure Participants	30	33
Count of Participants [Participants]	27 90%	28 84.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zanubrutinib + Supportive Care, Placebo + Supportive Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4099
	Comments
	Method	Unstratified 1-sided Fisher's exact test
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.61
	Confidence Interval	(2-Sided) 95%; 0.349 to 7.391
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Time to Breathing Room Air
Description	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.
Time Frame	Up to 7 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Measure Participants	30	33
Number [Events / total follow-up in days]	0.060	0.061

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Zanubrutinib + Supportive Care, Placebo + Supportive Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7619
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.918
	Confidence Interval	(2-Sided) 95%; 0.511 to 1.648
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants Experiencing Respiratory Failure or Death
Description	Number of participants experiencing respiratory failure or death on or before Day 28
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Measure Participants	30	33
Count of Participants [Participants]	3 10%	5 15.2%

4. Secondary Outcome

Title	Number of Participants With All-cause Mortality
Description	Number of participants with all-cause mortality on or before Day 28
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Measure Participants	30	33
Count of Participants [Participants]	2 6.7%	4 12.1%

5. Secondary Outcome

Title	Number of Participants Discharged Alive
Description	Number of participants discharged alive on or before Day 28
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Measure Participants	30	33
Count of Participants [Participants]	26 86.7%	28 84.8%

6. Secondary Outcome

Title	Number of Participants Discharged Alive From the ICU
Description	Number of participants discharged alive from the intensive care unit (ICU) on or before Day 28
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Measure Participants	14	13
Count of Participants [Participants]	3 10%	2 6.1%

7. Secondary Outcome

Title	Number of Participants With Improvement in the World Health Organization (WHO) 8-point Ordinal Scale
Description	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.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Measure Participants	30	33
Count of Participants [Participants]	22 73.3%	25 75.8%

8. Secondary Outcome

Title	Duration of Mechanical Ventilation
Description	Number of days on mechanical ventilation on or before Day 28
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Measure Participants	3	4
Median (Full Range) [Days]	4.0	13.5

9. Secondary Outcome

Title	Duration of Hospitalization
Description	Number of days hospitalized on or before Day 28
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Measure Participants	30	33
Median (Full Range) [Days]	6.5	5.0

10. Secondary Outcome

Title	PaO2:FiO2 Ratio
Description	Partial pressure of oxygen (PaO2):fraction of inspired oxygen (FiO2) ratio
Time Frame	Baseline, Day 7, Day 14, Day 21 and Day 28

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Measure Participants	3	3
Baseline	53.0
Day 7	82.00	54.00
Day 14	32.00	90.60
Day 21	52.10

11. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	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
Time Frame	Up to 7 months

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Zanubrutinib + Supportive Care	Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.	Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
Measure Participants	30	29
At least one TEAE	19 63.3%	20 60.6%
Grade 3 or higher	6 20%	6 18.2%
Serious adverse event	4 13.3%	7 21.2%
Treatment-related TEAE	2 6.7%	1 3%

Adverse Events

Time Frame	Up to 7 months
Adverse Event Reporting Description	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.
Arm/Group Title	Zanubrutinib + Supportive Care		Placebo + Supportive Care
Arm/Group Description	Zanubrutinib 320 mg orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.		Placebo orally once daily for 28 days. Supportive care treatment selected and administered as deemed appropriate by the study investigator.
All Cause Mortality
	Zanubrutinib + Supportive Care		Placebo + Supportive Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/30 (10%)		4/33 (12.1%)
Serious Adverse Events
	Zanubrutinib + Supportive Care		Placebo + Supportive Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/30 (13.3%)		7/29 (24.1%)
Blood and lymphatic system disorders
Anaemia	0/30 (0%)	0	1/29 (3.4%)	1
Cardiac disorders
Right ventricular failure	0/30 (0%)	0	1/29 (3.4%)	1
Infections and infestations
COVID-19 pneumonia	1/30 (3.3%)	1	0/29 (0%)	0
Septic shock	0/30 (0%)	0	0/29 (0%)	0
Metabolism and nutrition disorders
Hypernatraemia	0/30 (0%)	0	0/29 (0%)	0
Nervous system disorders
Haemorrhage intracranial	0/30 (0%)	0	0/29 (0%)	0
Ischaemic stroke	0/30 (0%)	0	1/29 (3.4%)	1
Renal and urinary disorders
Acute kidney injury	1/30 (3.3%)	1	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/30 (0%)	0	0/29 (0%)	0
Dyspnoea	0/30 (0%)	0	1/29 (3.4%)	1
Hypoxia	1/30 (3.3%)	1	2/29 (6.9%)	2
Pulmonary embolism	1/30 (3.3%)	1	1/29 (3.4%)	1
Respiratory distress	0/30 (0%)	0	1/29 (3.4%)	1
Respiratory failure	2/30 (6.7%)	2	2/29 (6.9%)	2
Vascular disorders
Distributive shock	1/30 (3.3%)	1	0/29 (0%)	0
Other (Not Including Serious) Adverse Events
	Zanubrutinib + Supportive Care		Placebo + Supportive Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/30 (63.3%)		20/29 (69%)
Blood and lymphatic system disorders
Anaemia	1/30 (3.3%)	1	1/29 (3.4%)	1
Leukocytosis	1/30 (3.3%)	1	0/29 (0%)	0
Pancytopenia	1/30 (3.3%)	1	0/29 (0%)	0
Thrombocytopenia	1/30 (3.3%)	1	0/29 (0%)	0
Cardiac disorders
Atrial fibrillation	0/30 (0%)	0	1/29 (3.4%)	1
Bradycardia	5/30 (16.7%)	5	0/29 (0%)	0
Extrasystoles	1/30 (3.3%)	1	0/29 (0%)	0
Sinus bradycardia	1/30 (3.3%)	1	0/29 (0%)	0
Sinus tachycardia	1/30 (3.3%)	1	0/29 (0%)	0
Tachycardia	1/30 (3.3%)	1	1/29 (3.4%)	1
Eye disorders
Vision blurred	1/30 (3.3%)	1	0/29 (0%)	0
Gastrointestinal disorders
Ascites	1/30 (3.3%)	1	0/29 (0%)	0
Constipation	2/30 (6.7%)	2	2/29 (6.9%)	2
Diarrhoea	2/30 (6.7%)	2	1/29 (3.4%)	1
Dyspepsia	1/30 (3.3%)	1	1/29 (3.4%)	1
Flatulence	1/30 (3.3%)	1	0/29 (0%)	0
Gastric ulcer haemorrhage	0/30 (0%)	0	1/29 (3.4%)	1
Nausea	2/30 (6.7%)	2	0/29 (0%)	0
Rectal haemorrhage	1/30 (3.3%)	1	0/29 (0%)	0
General disorders
Fatigue	1/30 (3.3%)	1	0/29 (0%)	0
General physical health deterioration	0/30 (0%)	0	1/29 (3.4%)	1
Oedema peripheral	1/30 (3.3%)	1	0/29 (0%)	0
Peripheral swelling	0/30 (0%)	0	1/29 (3.4%)	1
Hepatobiliary disorders
Ischaemic hepatitis	0/30 (0%)	0	1/29 (3.4%)	1
Infections and infestations
Acute sinusitis	0/30 (0%)	0	1/29 (3.4%)	1
Bacteraemia	0/30 (0%)	0	1/29 (3.4%)	1
Cellulitis	1/30 (3.3%)	1	0/29 (0%)	0
Epstein-Barr virus infection	1/30 (3.3%)	1	0/29 (0%)	0
Herpes simplex	0/30 (0%)	0	1/29 (3.4%)	1
Parotitis	1/30 (3.3%)	1	0/29 (0%)	0
Pneumonia bacterial	1/30 (3.3%)	1	0/29 (0%)	0
Sepsis	1/30 (3.3%)	1	0/29 (0%)	0
Urinary tract infection	1/30 (3.3%)	1	0/29 (0%)	0
Investigations
Alanine aminotransferase increased	0/30 (0%)	0	1/29 (3.4%)	1
Hepatic enzyme increased	1/30 (3.3%)	1	0/29 (0%)	0
Lymphocyte count decreased	1/30 (3.3%)	1	0/29 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/30 (3.3%)	1	0/29 (0%)	0
Hyperglycaemia	2/30 (6.7%)	2	1/29 (3.4%)	1
Hypoalbuminaemia	1/30 (3.3%)	3	2/29 (6.9%)	4
Hypoglycaemia	1/30 (3.3%)	1	0/29 (0%)	0
Hypokalaemia	3/30 (10%)	3	1/29 (3.4%)	1
Hypomagnesaemia	0/30 (0%)	0	3/29 (10.3%)	3
Hypophagia	1/30 (3.3%)	1	0/29 (0%)	0
Hypophosphataemia	1/30 (3.3%)	1	0/29 (0%)	0
Vitamin D deficiency	0/30 (0%)	0	1/29 (3.4%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/30 (3.3%)	1	0/29 (0%)	0
Groin pain	1/30 (3.3%)	1	0/29 (0%)	0
Muscle spasms	1/30 (3.3%)	1	0/29 (0%)	0
Pain in extremity	0/30 (0%)	0	2/29 (6.9%)	2
Rhabdomyolysis	1/30 (3.3%)	1	0/29 (0%)	0
Nervous system disorders
Headache	1/30 (3.3%)	1	3/29 (10.3%)	3
Intensive care unit acquired weakness	1/30 (3.3%)	1	0/29 (0%)	0
Psychiatric disorders
Depression	0/30 (0%)	0	1/29 (3.4%)	1
Renal and urinary disorders
Haematuria	0/30 (0%)	0	1/29 (3.4%)	1
Micturition urgency	1/30 (3.3%)	1	0/29 (0%)	0
Reproductive system and breast disorders
Vaginal haemorrhage	0/30 (0%)	0	1/29 (3.4%)	1
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/30 (3.3%)	1	0/29 (0%)	0
Hypoxia	0/30 (0%)	0	2/29 (6.9%)	2
Nasal discomfort	1/30 (3.3%)	1	0/29 (0%)	0
Oropharyngeal pain	0/30 (0%)	0	1/29 (3.4%)	1
Pleuritic pain	1/30 (3.3%)	1	0/29 (0%)	0
Pulmonary hypertension	0/30 (0%)	0	1/29 (3.4%)	1
Wheezing	0/30 (0%)	0	1/29 (3.4%)	1
Skin and subcutaneous tissue disorders
Alopecia	1/30 (3.3%)	1	0/29 (0%)	0
Decubitus ulcer	1/30 (3.3%)	1	0/29 (0%)	0
Rash macular	1/30 (3.3%)	1	0/29 (0%)	0
Vascular disorders
Deep vein thrombosis	0/30 (0%)	0	1/29 (3.4%)	1
Hypovolaemic shock	1/30 (3.3%)	1	0/29 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.