Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Neutralizing Antibody BGB-DXP593 in Participants With Mild-to-Moderate Coronavirus Disease 2019 (COVID-19)

• Sponsor: BeiGene (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04551898
• Collaborator: (none)
• Enrollment: 181
• Locations: 18
• Arms: 4
• Actual Duration (Months): 5.7
• Patients Per Site: 10.1
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

The primary objective of this study is to evaluate the efficacy of BGB-DXP593 administered intravenously as a single dose in participants with mild to moderate COVID-19

Condition or Disease	Intervention/Treatment	Phase
Covid19	Drug: BGB-DXP593; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 181 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 to Evaluate the Efficacy and Safety of SARS-CoV-2 Neutralizing Antibody BGB-DXP593 in Patients With Mild-to-Moderate COVID-19
• Actual Study Start Date: Dec 2, 2020
• Actual Primary Completion Date: May 25, 2021
• Actual Study Completion Date: May 25, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BGB-DXP593 Low Dose Participants will receive BGB-DXP593 on Day 1, and followed up for safety for up to 85 days	Drug: BGB-DXP593; Intravenous (IV) infusion administered over 30 to 90 minutes at a dose as specified in the treatment arm
Experimental: BGB-DXP593 Medium Dose Participants will receive BGB-DXP593 on Day 1, and followed up for safety for up to 85 days	Drug: BGB-DXP593; Intravenous (IV) infusion administered over 30 to 90 minutes at a dose as specified in the treatment arm
Experimental: BGB-DXP593 High Dose Participants will receive BGB-DXP593 on Day 1, and followed up for safety for up to 85 days	Drug: BGB-DXP593; Intravenous (IV) infusion administered over 30 to 90 minutes at a dose as specified in the treatment arm
Placebo Comparator: Placebo Participants will receive placebo on Day 1, and followed up for safety for up to 85 days	Drug: Placebo; Placebo to match BGB-DXP593 administered as specified in the treatment arm

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Day 8 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Shedding [Baseline and Day 8]

   SARS-CoV-2 viral shedding was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal swab samples.

Secondary Outcome Measures

1. Time-Weighted Average Change in SARS-CoV-2 Viral Shedding From Baseline to Day 15 [Baseline and Day 15]

2. Change in SARS-CoV-2 Viral Shedding From Baseline to Day 15 [Baseline and Day 15]

   SARS-CoV-2 viral shedding was measured by RT-qPCR in nasopharyngeal swab samples

3. Time to Negative RT-qPCR in All Tested Samples [From Baseline up to Day 21]

   The negative RT-qPCR is defined as the value that is below the lower limit of detection

4. Percentage of Participants Who Required Hospitalization Due to Worsened COVID-19 [Baseline up to End of Study (EOS) /174 Days]

5. Time to Resolution of All COVID-19-Related Symptoms [Baseline up to EOS /174 Days]

6. All-Cause Mortality at Day 29 [Day 29]

   Number of participants that died by Day 29

7. Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Up to 174 days]

8. Maximum Observed Plasma Concentration (Cmax) of BGB-DXP593 [Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to174 days)]

9. Area Under the Plasma Concentration-time Curve (AUC) of BGB-DXP593 From Time 0 to Day 29 [Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, and 29]

10. Area Under the Plasma Concentration-time Curve (AUC) of BGB-DXP593 [Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to 174 days)]

    AUClast : AUC from time zero to the time of the last quantifiable concentration AUCinf: AUC from zero to infinite time with extrapolation of the terminal phase

11. Time to Reach Cmax (Tmax) of BGB-DXP593 [Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to 174 days)]

12. Terminal Half-Life (t1/2) of BGB-DXP593 [Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to 174 days)]

13. Clearance (CL) of BGB-DXP593 [Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to 174 days)]

14. Volume of Distribution During the Terminal Phase (Vz) of BGB-DXP593 [Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to 174 days)]

15. Number of Participants With Anti-drug Antibodies (ADAs) to BGB-DXP593 [Day 1 (pre-dose) Days 15, 29, and End of study visit (up to 174 days)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

1. Laboratory-confirmed severe acute respiratory syndrome (SARS)-CoV-2 infection (positive reverse transcription-polymerase chain reaction [RT-PCR] test or other authorized antigen testing methods) in any samples following local practice ≤ 72 hours prior to screening.

2. Have experienced COVID-19 symptoms for ≤ 7 days prior to treatment assignment, such as fever, cough, shortness of breath, sore throat, diarrhea, vomiting, and dysgeusia

3. Agree to the collection of nasopharyngeal swabs, saliva, and venous blood

Key Exclusion Criteria:

1. Severe COVID-19 having oxygen saturation (SpO2) ≤ 93 % on room air at sea level or ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to fractional inspired oxygen (FiO2) < 300, respiratory rate ≥ 30/min, heart rate ≥ 125/min

2. Requires mechanical ventilation or anticipated impending need for mechanical ventilation

3. Known allergies to any of the components used in the formulation of the interventions

4. Have received an investigational intervention for SARS-CoV-2 prophylaxis within 30 days before dosing

5. Have received treatment with a SARS-CoV-2 specific monoclonal antibody

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Midland Florida Clinical Research Center, LLC	DeLand	Florida	United States	32720
2	Baptist Medical Center	Jacksonville	Florida	United States	33207
3	Homestead Associates in Research Inc.	Miami	Florida	United States	33032
4	Medical Research Center of Miami II, Inc.	Miami	Florida	United States	33134
5	US Associates in Research	Miami	Florida	United States	33175
6	Continental Research Network	Miami	Florida	United States	33187
7	Omega Research Orlando	Orlando	Florida	United States	32808
8	Revival Research Institute, LLC.	Dearborn	Michigan	United States	48126
9	New Phase Research & Development	Knoxville	Tennessee	United States	37909
10	Amarillo Center for Clinical Research	Amarillo	Texas	United States	79124
11	PanAmerican Clinical Research	Brownsville	Texas	United States	78520
12	Fundação Universidade de Caxias do Sul - Instituto de Pesquisas em Saúde	Petropolis	Caxias Do Sul	Brazil	95070
13	Hospital das Clínicas da Faculdade de Medicina de Botucatu	Botucatu		Brazil	18618
14	CMPC Pesquisa Clinica	Sorocaba		Brazil	18040
15	Hospital Cardiologica Aguascalientes	Aguascalientes		Mexico	20230
16	Iecsi S.C.	Monterrey		Mexico	58249
17	TASK	Cape Town		South Africa	7500
18	Langeberg Clinical Trials	Cape Town		South Africa	7570

Sponsors and Collaborators

• BeiGene

Investigators

• Principal Investigator: Study Director, BeiGene

Study Documents (Full-Text)

• Study Protocol - Oct 27, 2020
• Statistical Analysis Plan - Mar 4, 2021

More Information

Publications

None provided.

• Responsible Party: BeiGene
• ClinicalTrials.gov Identifier: NCT04551898
• Other Study ID Numbers: BGB-DXP593-102
• First Posted: Sep 16, 2020
• Last Update Posted: Mar 17, 2022
• Last Verified: Mar 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
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Recruitment Details	This study was conducted in 20 centers and 181 participants were treated.

Arm/Group Title	Placebo	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of placebo solution administered over 30 to 90 minutes	Single intravenous infusion of 5 milligrams/kilogram (mg/kg) DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Period Title: Overall Study
STARTED	47	45	43	46
COMPLETED	39	42	35	41
NOT COMPLETED	8	3	8	5

Baseline Characteristics

Arm/Group Title	Placebo	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg	Total
Arm/Group Description	Single intravenous infusion of placebo solution administered over 30 to 90 minutes	Single intravenous infusion of 5 mg/kg DXP593 administered over 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered over 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered over 30 to 90 minutes	Total of all reporting groups
Overall Participants	47	45	43	46	181
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	44.3 (14.02)	46.2 (15.56)	43.6 (12.43)	41.1 (13.35)	43.8 (13.91)
Sex: Female, Male (Count of Participants)
Female	20 42.6%	17 37.8%	22 51.2%	27 58.7%	86 47.5%
Male	27 57.4%	28 62.2%	21 48.8%	19 41.3%	95 52.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	3 6.4%	2 4.4%	1 2.3%	2 4.3%	8 4.4%
Asian	0 0%	1 2.2%	0 0%	0 0%	1 0.6%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	3 6.4%	5 11.1%	2 4.7%	5 10.9%	15 8.3%
White	40 85.1%	35 77.8%	39 90.7%	33 71.7%	147 81.2%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 2.1%	2 4.4%	1 2.3%	6 13%	10 5.5%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Day 8 in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Viral Shedding
Description	SARS-CoV-2 viral shedding was measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in nasopharyngeal swab samples.
Time Frame	Baseline and Day 8

Outcome Measure Data

Analysis Population Description

Intent To Treat (ITT) analysis set. Participants with available data were included in the analysis.

Arm/Group Title	Placebo	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of placebo solution administered over 30 to 90 minutes	Single intravenous infusion of 5 mg/kg DXP593 administered over 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered over 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered over 30 to 90 minutes
Measure Participants	41	42	34	42
Mean (Standard Deviation) [log10 copies/ml]	-2.88 (2.241)	-3.52 (2.831)	-3.75 (2.513)	-3.03 (2.239)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, BGB-DXP593 5 mg/kg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4829
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least square Mean
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 90%; -0.84 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, BGB-DXP593 15 mg/kg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1739
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least square Mean
	Estimated Value	-0.51
	Confidence Interval	(2-Sided) 90%; -1.13 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, BGB-DXP593 30 mg/kg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6006
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least square Mean
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 90%; -0.40 to 0.77
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, BGB-DXP593 5 mg/kg, BGB-DXP593 15 mg/kg, BGB-DXP593 30 mg/kg
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4996
	Comments	H0: there is a flat dose response curve comparing change from baseline to Day 8 in viral load in the Placebo and other BGB-DXP593 dose groups
	Method	t-test, 1 sided
	Comments	MCP Mod was used to test the primary hypothesis and provide 1-sided p-value accordingly.

2. Secondary Outcome

Title	Time-Weighted Average Change in SARS-CoV-2 Viral Shedding From Baseline to Day 15
Time Frame	Baseline and Day 15

Outcome Measure Data

Analysis Population Description

ITT analysis set. Participants with available samples were included in the analysis.

Arm/Group Title	Placebo	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of placebo solution administered over 30 to 90 minutes	Single intravenous infusion of 5 mg/kg DXP593 administered over 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered over 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered over 30 to 90 minutes
Measure Participants	45	43	37	44
Mean (Standard Deviation) [log10 copies/ml]	-2.56 (1.718)	-2.93 (1.997)	-2.87 (2.049)	-2.55 (1.785)

3. Secondary Outcome

Title	Change in SARS-CoV-2 Viral Shedding From Baseline to Day 15
Description	SARS-CoV-2 viral shedding was measured by RT-qPCR in nasopharyngeal swab samples
Time Frame	Baseline and Day 15

Outcome Measure Data

Analysis Population Description

ITT analysis set. Participants with available samples were included in the analysis.

Arm/Group Title	Placebo	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of placebo solution administered over 30 to 90 minutes	Single intravenous infusion of 5 mg/kg DXP593 administered over 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered over 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered over 30 to 90 minutes
Measure Participants	41	41	32	42
Mean (Standard Deviation) [log10 copies/ml]	-4.16 (2.446)	-4.29 (2.675)	-4.31 (2.851)	-4.04 (2.577)

4. Secondary Outcome

Title	Time to Negative RT-qPCR in All Tested Samples
Description	The negative RT-qPCR is defined as the value that is below the lower limit of detection
Time Frame	From Baseline up to Day 21

Outcome Measure Data

Analysis Population Description

ITT analysis set

Arm/Group Title	Placebo	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of placebo solution administered over 30 to 90 minutes	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	47	45	43	46
Median (90% Confidence Interval) [Days]	17.00	15.00	10.00	17.00

5. Secondary Outcome

Title	Percentage of Participants Who Required Hospitalization Due to Worsened COVID-19
Time Frame	Baseline up to End of Study (EOS) /174 Days

Outcome Measure Data

Analysis Population Description

ITT analysis set

Arm/Group Title	Placebo	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of placebo solution administered over 30 to 90 minutes	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	47	45	43	46
Number [Percentage of participants]	4.3 9.1%	2.2 4.9%	2.3 5.3%	0.0 0%

6. Secondary Outcome

Title	Time to Resolution of All COVID-19-Related Symptoms
Time Frame	Baseline up to EOS /174 Days

Outcome Measure Data

Analysis Population Description

ITT analysis set

Arm/Group Title	Placebo	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of placebo solution administered over 30 to 90 minutes	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	47	45	43	46
Median (90% Confidence Interval) [Days]	16.5	15.0	19.0	14.0

7. Secondary Outcome

Title	All-Cause Mortality at Day 29
Description	Number of participants that died by Day 29
Time Frame	Day 29

Outcome Measure Data

Analysis Population Description

ITT analysis set

Arm/Group Title	Placebo	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of placebo solution administered over 30 to 90 minutes	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	47	45	43	46
Number [Percentage of participants]	2.13 4.5%	0 0%	0 0%	0 0%

8. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame	Up to 174 days

Outcome Measure Data

Analysis Population Description

Safety analysis set includes all participants who received the study drug or placebo.

Arm/Group Title	Placebo	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of placebo solution administered over 30 to 90 minutes	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	47	44	40	45
With at Least One TEAE	6 12.8%	6 13.3%	4 9.3%	7 15.2%
Grade 3 or Higher TEAE	1 2.1%	1 2.2%	1 2.3%	0 0%
Serious TEAE	2 4.3%	2 4.4%	1 2.3%	0 0%

9. Secondary Outcome

Title	Maximum Observed Plasma Concentration (Cmax) of BGB-DXP593
Time Frame	Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to174 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis set includes all participants who have received the study drug per protocol and for whom PK data are available.

Arm/Group Title	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	42	40	44
Mean (Standard Deviation) [µg/mL]	132.95 (53.180)	368.22 (232.040)	714.17 (149.198)

10. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC) of BGB-DXP593 From Time 0 to Day 29
Time Frame	Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, and 29

Outcome Measure Data

Analysis Population Description

PK analysis set includes all participants who have received the study drug per protocol and for whom PK data are available.

Arm/Group Title	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	42	37	45
Median (Full Range) [day*μg/mL]	1188.7	3014.3	6609.2

11. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve (AUC) of BGB-DXP593
Description	AUClast : AUC from time zero to the time of the last quantifiable concentration AUCinf: AUC from zero to infinite time with extrapolation of the terminal phase
Time Frame	Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to 174 days)

Outcome Measure Data

Analysis Population Description

PK analysis set includes all participants who have received the study drug per protocol and for whom PK data are available.

Arm/Group Title	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	43	40	45
AUClast	1829.3	4707.5	10259.5
AUCInf	2098.7	4996.3	10509.2

12. Secondary Outcome

Title	Time to Reach Cmax (Tmax) of BGB-DXP593
Time Frame	Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to 174 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis set includes all participants who have received the study drug per protocol and for whom PK data are available.

Arm/Group Title	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	43	40	45
Median (Full Range) [hours]	1.500	1.500	1.500

13. Secondary Outcome

Title	Terminal Half-Life (t1/2) of BGB-DXP593
Time Frame	Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to 174 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis set includes all participants who have received the study drug per protocol and for whom PK data are available.

Arm/Group Title	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	38	35	40
Median (Full Range) [Day]	21.4	23.2	20.8

14. Secondary Outcome

Title	Clearance (CL) of BGB-DXP593
Time Frame	Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to 174 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis set includes all participants who have received the study drug per protocol and for whom PK data are available.

Arm/Group Title	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	38	35	40
Median (Full Range) [Liters/Day]	0.21	0.25	0.24

15. Secondary Outcome

Title	Volume of Distribution During the Terminal Phase (Vz) of BGB-DXP593
Time Frame	Day 1 (pre-dose, End of Infusion) Days 3, 8, 15, 29, and End of study visit (up to 174 days)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) analysis set includes all participants who have received the study drug per protocol and for whom PK data are available.

Arm/Group Title	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	38	35	40
Median (Full Range) [Liters]	6.58	8.07	7.33

16. Secondary Outcome

Title	Number of Participants With Anti-drug Antibodies (ADAs) to BGB-DXP593
Time Frame	Day 1 (pre-dose) Days 15, 29, and End of study visit (up to 174 days)

Outcome Measure Data

Analysis Population Description

The ADA Analysis Set includes all the participants who have received the study drug and in whom both baseline ADA and at least 1 postbaseline ADA results are available

Arm/Group Title	BGB-DXP593 5 mg/kg	BGB-DXP593 15 mg/kg	BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes	Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
Measure Participants	44	37	45
Treatment Induced	1 2.1%	0 0%	0 0%
Neutralizing antibody Positive	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Up to 174 days
Adverse Event Reporting Description	Safety Analysis Set included all participants who received the study drug or placebo.
Arm/Group Title	Placebo		BGB-DXP593 5 mg/kg		BGB-DXP593 15 mg/kg		BGB-DXP593 30 mg/kg
Arm/Group Description	Single intravenous infusion of placebo solution administered over 30 to 90 minutes		Single intravenous infusion of 5 mg/kg DXP593 administered for 30 to 90 minutes		Single intravenous infusion of 15 mg/kg DXP593 administered for 30 to 90 minutes		Single intravenous infusion of 30 mg/kg DXP593 administered for 30 to 90 minutes
All Cause Mortality
	Placebo		BGB-DXP593 5 mg/kg		BGB-DXP593 15 mg/kg		BGB-DXP593 30 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/47 (2.1%)		0/44 (0%)		0/40 (0%)		0/45 (0%)
Serious Adverse Events
	Placebo		BGB-DXP593 5 mg/kg		BGB-DXP593 15 mg/kg		BGB-DXP593 30 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/47 (4.3%)		2/44 (4.5%)		1/40 (2.5%)		0/45 (0%)
Infections and infestations
COVID-19 pneumonia	2/47 (4.3%)	2	2/44 (4.5%)	2	1/40 (2.5%)	1	0/45 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		BGB-DXP593 5 mg/kg		BGB-DXP593 15 mg/kg		BGB-DXP593 30 mg/kg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/47 (10.6%)		4/44 (9.1%)		4/40 (10%)		7/45 (15.6%)
Cardiac disorders
Tachycardia	1/47 (2.1%)	1	1/44 (2.3%)	1	0/40 (0%)	0	0/45 (0%)	0
Ear and labyrinth disorders
Ear pruritus	0/47 (0%)	0	0/44 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1
Gastrointestinal disorders
Diarrhoea	0/47 (0%)	0	0/44 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1
Gastritis	0/47 (0%)	0	1/44 (2.3%)	1	0/40 (0%)	0	0/45 (0%)	0
Nausea	0/47 (0%)	0	2/44 (4.5%)	2	0/40 (0%)	0	3/45 (6.7%)	3
Vomiting	0/47 (0%)	0	0/44 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1
General disorders
Medical device site hypersensitivity	1/47 (2.1%)	1	0/44 (0%)	0	0/40 (0%)	0	0/45 (0%)	0
Infections and infestations
Urinary tract infection	0/47 (0%)	0	0/44 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0
Injury, poisoning and procedural complications
Toxicity to various agents	0/47 (0%)	0	0/44 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1
Investigations
Alanine aminotransferase increased	0/47 (0%)	0	0/44 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0
Aspartate aminotransferase increased	0/47 (0%)	0	0/44 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0
Fibrin D dimer increased	1/47 (2.1%)	1	0/44 (0%)	0	0/40 (0%)	0	0/45 (0%)	0
Metabolism and nutrition disorders
Hypoglycaemia	1/47 (2.1%)	1	0/44 (0%)	0	0/40 (0%)	0	0/45 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	1/47 (2.1%)	1	0/44 (0%)	0	0/40 (0%)	0	0/45 (0%)	0
Nervous system disorders
Dizziness	0/47 (0%)	0	0/44 (0%)	0	1/40 (2.5%)	1	0/45 (0%)	0
Dysgeusia	0/47 (0%)	0	0/44 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1
Headache	0/47 (0%)	0	0/44 (0%)	0	1/40 (2.5%)	1	1/45 (2.2%)	1
Skin and subcutaneous tissue disorders
Erythema multiforme	0/47 (0%)	0	0/44 (0%)	0	0/40 (0%)	0	1/45 (2.2%)	1

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.