Clinical trial NCT04532294
Conditions: Covid19
Sponsor: BeiGene
Start date: 2020-09-08; Completion date: 2021-02-13
Enrollment: 18 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The primary purpose of this study is to investigate the safety and tolerability of BGB-DXP593 administered intravenously as a single dose in healthy participants

Detailed description:

Arms: arm 1: Participants will receive BGB-DXP593 10 mg/kg on Day 1 arm 2: Participants will receive BGB-DXP593 30 mg/kg on Day 1 arm 3: Placebo to match (PTM) BGB-DXP593 on Day 1
Interventions: intervention 1: BGB DXP593 intervention 2: Placebo
Intervention descriptions: intervention 1: Administered intravenously (IV) as specified in the treatment arm intervention 2: Placebo to match BGB-DXP593

Protocol documents:
Prot_000.pdf: 
BGB-DXP593-101 
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Original Protocol Version 0.0 
04 August 2020 
 
CONFIDENTIAL 
Page 1 
CLINICAL STUDY PROTOCOL 
Protocol Title:  
A First-in-Human, Randomized, Double-Blind, 
Placebo-Controlled, Single Dose Escalation Study to 
Evaluate the Safety, Tolerability, Pharmacokinetics, and 
Immunogenicity of SARS-CoV-2 Neutralizing Antibody 
BGB-DXP593 in Healthy Subjects 
Protocol Identifier: 
BGB-DXP593-101 
Phase: 
1 
Investigational Product: 
BGB-DXP593  
Proposed Indication: 
Not Applicable 
Sponsor: 
BeiGene, Ltd.  
c/o BeiGene AUS Pty Ltd. 
1C/528 Compton Road Stretton 
Queensland 4116, Australia 
Sponsor Medical Monitor 
 
Original Protocol Version 0.0: 
04 August 2020 
 
 
 
 
 
 
 
Confidentiality Statement 
This Document Is Not for Distribution – Do Not Copy 
This document contains confidential information and is the proprietary property of BeiGene, Ltd., and its 
subsidiaries.  This document is for use by individuals and their designated representatives for their 
confidential review, consideration, and/or participation in investigational trial(s).  This document may not 
be copied or distributed for review by any unauthorized individuals without the prior written authorization 
of BeiGene, Ltd., or one of its subsidiaries.  Your acceptance of this document constitutes agreement that 
you will not disclose the information contained herein to others without the prior written authorization 
from BeiGene, Ltd., or one of its subsidiaries. 
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INVESTIGATOR SIGNATURE PAGE 
Protocol Title: 
A First-in-Human, Randomized, Double-Blind, 
Placebo-Controlled, Single Dose Escalation Study to Evaluate 
the Safety, Tolerability, Pharmacokinetics, and Immunogenicity 
of SARS-CoV-2 Neutralizing Antibody BGB-DXP593 in 
Healthy Subjects  
Protocol Identifier:  
BGB-DXP593-101 
 
This protocol is a confidential communication of BeiGene, Ltd., and its subsidiaries. I confirm 
that I have read this protocol, I understand it, and I will work according to this protocol and the 
terms of the clinical study agreement governing the study. I will also work consistently with the 
ethical principles that have their origin in the Declaration of Helsinki and that are consistent with 
good clinical practices and the applicable laws and regulations. Acceptance of this document 
constitutes my agreement that no unpublished information contained herein will be published or 
disclosed without prior written approval from BeiGene, Ltd., or one of its subsidiaries. 
 
Instructions for Investigator:  Please SIGN and DATE this signature page prior to 
implementation of this sponsor-approved protocol.  PRINT your name, title, and the name and 
address of the center in which the study will be conducted.  
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
Signature of Investigator:  
 
Date:  
Printed Name: 
 
 
 
Investigator Title: 
 
 
 
Name/Address of Center: 
 
 
 
 
 
 
 
 
 
 
 
 
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TABLE OF CONTENTS 
FINAL PROTOCOL APPROVAL SHEET ....................................................................................2 
INVESTIGATOR SIGNATURE PAGE .........................................................................................3 
TABLE OF CONTENTS .................................................................................................................4 
LIST OF TABLES ...........................................................................................................................9 
LIST OF FIGURE............................................................................................................................9 
SYNOPSIS ....................................................................................................................................10 
LIST OF ABBREVIATIONS AND TERMS ................................................................................14 
1. 
INTRODUCTION AND RATIONALES ..................................................................15 
1.1. 
Introduction .................................................................................................................15 
1.2. 
BGB-DXP593 as a SARS-CoV-2 Neutralizing Monoclonal Antibody .....................15 
1.2.1. 
Summary of Relevant Nonclinical Data with BGB-DXP593 ....................................15 
1.2.1.1. 
Pharmacology .............................................................................................................15 
1.2.1.2. 
Toxicology ..................................................................................................................16 
1.2.2. 
Summary of Relevant Clinical Experience with BGB-DXP593 ................................17 
1.3. 
Study Rationale ...........................................................................................................17 
1.3.1. 
Rationale for Matching Placebo as the Comparator ...................................................17 
1.3.2. 
Rationale for BGB-DXP593 Starting Dose ................................................................17 
1.3.2.1. 
Allometric Scaling for Human Pharmacokinetics Projection .....................................17 
1.3.2.2. 
Recommendation of the First-in-Human Dose of BGB-DXP593 in Healthy 
Subjects .......................................................................................................................19 
1.3.3. 
Rationale for Pharmacokinetic Sampling ...................................................................19 
1.4. 
Benefit-Risk Assessment ............................................................................................19 
1.5. 
Study Conduct ............................................................................................................20 
2. 
STUDY OBJECTIVES AND STUDY ENDPOINTS ...............................................21 
2.1. 
Study Objectives .........................................................................................................21 
2.1.1. 
Primary Objective .......................................................................................................21 
2.1.2. 
Secondary Objectives .................................................................................................21 
2.2. 
Study Endpoints ..........................................................................................................21 
2.2.1. 
Primary Endpoint ........................................................................................................21 
2.2.2. 
Secondary Endpoints ..................................................................................................21 
3. 
STUDY DESIGN .......................................................................................................22 
3.1. 
Summary of Study Design ..........................................................................................22 
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3.2. 
Details of Dose Escalation ..........................................................................................23 
3.2.1. 
Starting Dose and Dose Escalation Approach ............................................................23 
3.2.2. 
Rules for Dose Escalation ...........................................................................................23 
3.2.2.1. 
Escalation From Dose Level A to Dose Level B ........................................................23 
3.2.2.2. 
Potential Escalation From Dose Level B to Dose Level C .........................................24 
3.3. 
Criteria for Pausing Drug Administration and New Enrollment ................................24 
4. 
SELECTION OF STUDY POPULATION ................................................................25 
4.1. 
Inclusion Criteria ........................................................................................................25 
4.2. 
Exclusion Criteria .......................................................................................................25 
5. 
STUDY TREATMENT ..............................................................................................28 
5.1. 
Formulation, Packaging, and Handling ......................................................................28 
5.1.1. 
BGB-DXP593 .............................................................................................................28 
5.1.2. 
Placebo ........................................................................................................................28 
5.2. 
Dosage, Administration, and Compliance ..................................................................28 
5.3. 
Measures to Minimize Bias: Randomization and Blinding ........................................29 
5.4. 
Incorrect Administration .............................................................................................30 
5.5. 
Dose Interruption or Modification ..............................................................................30 
6. 
PRIOR AND CONCOMITANT THERAPY .............................................................31 
6.1. 
Prior Therapy ..............................................................................................................31 
6.2. 
Concomitant Therapy .................................................................................................31 
6.3. 
Potential Interactions Between BGB-DXP593 and Concomitant Medications .........31 
7. 
STUDY PERIODS, VISITS, OR PROCEDURES ....................................................32 
7.1. 
Screening Period .........................................................................................................32 
7.1.1. 
Informed Consent .......................................................................................................32 
7.2. 
Enrollment ..................................................................................................................32 
7.2.1. 
Confirmation of Eligibility .........................................................................................32 
7.2.2. 
Subject Numbering .....................................................................................................32 
7.3. 
Check-in (Day -1) .......................................................................................................32 
7.4. 
Randomization ............................................................................................................32 
7.5. 
Treatment (Day 1) .......................................................................................................33 
7.6. 
Follow-up Period ........................................................................................................33 
7.6.1. 
Check-out (Day 8) ......................................................................................................33 
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7.6.2. 
End-of-Study Visit ......................................................................................................33 
7.6.3. 
Safety Follow-up Visit for Premature Study Discontinuation ....................................33 
7.6.4. 
Lost to Follow-up .......................................................................................................33 
7.7. 
Discontinuation From Study Treatment or From the Study .......................................33 
7.7.1. 
Subject Discontinuation From the Study Treatment ..................................................33 
7.7.2. 
Subject Discontinuation From the Study ....................................................................34 
7.8. 
End of Study ...............................................................................................................34 
8. 
STUDY ASSESSMENTS ..........................................................................................35 
8.1. 
Screening Assessments ...............................................................................................35 
8.1.1. 
Demographic Data, Medical History, and Prior Medications ....................................35 
8.2. 
Safety Assessments .....................................................................................................35 
8.2.1. 
Vital Signs ..................................................................................................................35 
8.2.2. 
Physical Examinations ................................................................................................35 
8.2.3. 
Laboratory Safety Tests ..............................................................................................36 
8.2.4. 
Electrocardiograms .....................................................................................................36 
8.2.5. 
Cardiac Telemetry ......................................................................................................36 
8.2.6. 
Adverse Events ...........................................................................................................36 
8.2.7. 
Serology ......................................................................................................................37 
8.2.8. 
Virology ......................................................................................................................37 
8.3. 
Pharmacokinetic Assessment and Antidrug Antibody Testing ..................................37 
8.4. 
Visit Windows ............................................................................................................37 
8.5. 
Unscheduled Visits .....................................................................................................38 
9. 
SAFETY MONITORING AND REPORTING .........................................................39 
9.1. 
Risks Associated With BGB-DXP593 .......................................................................39 
9.2. 
General Plan to Manage Safety Concerns ..................................................................39 
9.2.1. 
Eligibility Criteria .......................................................................................................39 
9.2.2. 
Safety Monitoring Plan ...............................................................................................39 
9.3. 
Adverse Events ...........................................................................................................40 
9.3.1. 
Definitions and Reporting ...........................................................................................40 
9.3.2. 
Assessment of Severity ...............................................................................................40 
9.3.3. 
Assessment of Causality .............................................................................................41 
9.3.4. 
Following Adverse Events and Serious Adverse Events ............................................41 
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9.3.5. 
Laboratory Test Abnormalities ...................................................................................42 
9.4. 
Definition of a Serious Adverse Event .......................................................................42 
9.5. 
Suspected Unexpected Serious Adverse Reaction .....................................................43 
9.6. 
Timing, Frequency, and Method of Capturing Adverse Events and Serious 
Adverse Events ...........................................................................................................43 
9.6.1. 
Adverse Event Reporting Period ................................................................................43 
9.6.2. 
Reporting of Serious Adverse Events .........................................................................44 
9.6.2.1. 
Prompt Reporting of Serious Adverse Events ............................................................44 
9.6.2.2. 
Completion and Transmission of the Serious Adverse Event Report ........................44 
9.6.2.3. 
Regulatory Reporting Requirements for Serious Adverse Events .............................44 
9.6.3. 
Eliciting Adverse Events ............................................................................................45 
9.6.4. 
Death ...........................................................................................................................45 
9.6.5. 
Pregnancies .................................................................................................................45 
9.6.6. 
Expedited Reporting to Health Authorities, Investigators, Institutional 
Review Boards, and Ethics Committees .....................................................................45 
9.6.7. 
Reporting Infusion-Related Reactions ........................................................................45 
9.7. 
Management of Infusion-Related Reactions and Severe Hypersensitivity 
Reactions .....................................................................................................................46 
9.7.1. 
Managing Infusion-Related Reactions .......................................................................46 
9.7.2. 
Severe Hypersensitivity Reactions .............................................................................47 
10. 
STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION .................48 
10.1. 
Statistical Analysis ......................................................................................................48 
10.1.1. 
Randomization Method ..............................................................................................48 
10.1.2. 
Analysis Sets ...............................................................................................................48 
10.1.3. 
Subject Disposition .....................................................................................................48 
10.1.4. 
Demographics and Other Baseline Characteristics .....................................................48 
10.1.5. 
Prior and Concomitant Therapy ..................................................................................48 
10.2. 
Efficacy Analyses .......................................................................................................49 
10.3. 
Safety Analyses ..........................................................................................................49 
10.3.1. 
Extent of Exposure .....................................................................................................49 
10.3.2. 
Adverse Events ...........................................................................................................49 
10.3.3. 
Laboratory Analyses ...................................................................................................49 
10.3.4. 
Vital Signs ..................................................................................................................50 
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10.3.5. 
Electrocardiogram .......................................................................................................50 
10.4. 
Pharmacokinetic Analyses ..........................................................................................50 
10.5. 
Immunogenicity Analyses ..........................................................................................50 
10.6. 
Sample Size Consideration .........................................................................................50 
10.7. 
Interim Analysis ..........................................................................................................50 
11. 
STUDY COMMITTEE ..............................................................................................51 
11.1. 
Safety Monitoring Committee ....................................................................................51 
12. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS ...............................................................................................52 
12.1. 
Access to Information for Monitoring ........................................................................52 
12.2. 
Access to Information for Auditing or Inspections ....................................................52 
13. 
QUALITY ASSURANCE AND QUALITY CONTROL .........................................53 
13.1. 
Regulatory Authority Approval ..................................................................................53 
13.2. 
Quality Assurance .......................................................................................................53 
13.3. 
Study Site Inspections.................................................................................................53 
13.4. 
Drug Accountability ...................................................................................................53 
14. 
ETHICS/PROTECTION OF HUMAN SUBJECTS ..................................................55 
14.1. 
Ethical Standard ..........................................................................................................55 
14.2. 
Institutional Review Board/Independent Ethics Committee ......................................55 
14.2.1. 
Protocol Amendments ................................................................................................55 
14.3. 
Informed Consent .......................................................................................................56 
14.4. 
Subject and Data Confidentiality ................................................................................56 
14.5. 
Financial Disclosure ...................................................................................................57 
15. 
DATA HANDLING AND RECORD KEEPING ......................................................58 
15.1. 
Data Collection and Management Responsibilities ....................................................58 
15.1.1. 
Data Entry in the Electronic Case Report Form .........................................................58 
15.1.2. 
Data Collection ...........................................................................................................58 
15.1.3. 
Data Management/Coding ..........................................................................................58 
15.2. 
Study Records Retention ............................................................................................59 
15.3. 
Protocol Deviations ....................................................................................................60 
15.4. 
Study Report and Publications....................................................................................60 
15.5. 
Study and Study Center Closure .................................................................................60 
15.6. 
Information Disclosure and Inventions ......................................................................61 
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16. 
REFERENCES ...........................................................................................................63 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ....................................................................64 
APPENDIX 2. SCHEDULE OF ASSESSMENTS FOR DAY 1 ...............................................67 
APPENDIX 3. PHARMACOKINETIC AND ANTIDRUG ANTIBODY BLOOD 
SAMPLING ................................................................................................................68 
APPENDIX 4. CLINICAL LABORATORY ASSESSMENTS ................................................69 
APPENDIX 5. CONTRACEPTION GUIDELINES AND DEFINITIONS OF 
“WOMEN OF CHILDBEARING POTENTIAL”, “NO CHILDBEARING 
POTENTIAL” .............................................................................................................70 
 
LIST OF TABLES 
Table 1: 
BGB-DXP593 Population PK Parameter Estimates in Cynomolgus Monkeys 
and Projected PK Parameters in Humans ...................................................................18 
Table 2: 
Projected Safety Margins at Proposed Doses in Humans ...........................................19 
Table 3: 
Planned Dose Levels and Number of Subjects ...........................................................22 
Table 4: 
Timeframe and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee .............................................................................44 
Table 5: 
Treatment Modifications for Symptoms of Infusion-Related Reactions Due 
to Study Drug ..............................................................................................................46 
 
LIST OF FIGURE 
Figure 1: 
Simulated BGB-DXP593 Serum Lung (Assuming 1% Biodistribution) 
Concentration-Time Profiles in Humans ....................................................................18 
 
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SYNOPSIS 
Name of Sponsor/Company:  BeiGene, Ltd. 
Investigational Product:  BGB-DXP593  
Title of Study:  A First-in-Human, Randomized, Double-Blind, Placebo-Controlled, Single Dose 
Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of 
SARS-CoV-2 Neutralizing Antibody BGB-DXP593 in Healthy Subjects 
Protocol Identifier:  BGB-DXP593-101 
Phase of Development:  1 
Number of Subjects: up to 30 healthy subjects 
Study Centers: 1 center in Australia  
Study Objectives  
Primary Objective 
• 
To investigate the safety and tolerability of BGB-DXP593 administered intravenously as a 
single dose in healthy subjects 
Secondary Objectives 
• 
To characterize the pharmacokinetic (PK) profile of BGB-DXP593 administered intravenously 
as a single dose at each dose level in healthy subjects 
• 
To evaluate the potential immunogenicity of BGB-DXP593 administered intravenously as a 
single dose at each dose level in healthy subjects 
 
Study Endpoints 
Primary Endpoint 
• 
Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent 
serious adverse events (SAEs)  
Secondary Endpoints 
• 
Changes in vital signs and 12-lead electrocardiogram (ECG) parameters from baseline 
• 
Incidence and magnitude of clinical laboratory abnormalities 
• 
Characterize PK concentration-time profile and PK parameters for BGB-DXP593: maximum 
observed concentration (Cmax), area under the concentration-time curve (AUC) from time zero 
to the time of the last quantifiable concentration (AUCt), AUC from time zero to infinity 
(AUCinf), AUC from time zero to Day 29 (AUC0-29), time to maximum observed concentration 
(tmax), terminal half-life (t1/2), clearance (CL), and volume of distribution (Vz) as appropriate 
• 
Clinical immunogenicity of BGB-DXP593 evaluated through the detection of antidrug 
antibodies (ADA) over time 
 
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Study Design  
This is a first-in-human, randomized, double-blind, placebo-controlled, single dose escalation study to 
investigate the safety, tolerability, PK, and immunogenicity of BGB-DXP593 in healthy subjects.  
After providing written informed consent, subjects will complete all the screening assessments. After 
being confirmed as eligible, subjects will be sequentially enrolled for different dose levels. Two dose 
levels are planned for eligible subjects to receive a single intravenous dose of study drug (ie, 
BGB-DXP593 or placebo) at 10 mg/kg or 30 mg/kg, respectively. Another higher dose level will be 
allowed for dose escalation.  
Enrollment will begin at the 10 mg/kg dose level. Escalation to the next dose level will occur 7 days 
after the last subject at the current dose level has received the study drug, and the safety, laboratory 
data have been reviewed.  
At each dose level, eligible subjects will be randomized at a 3:1 ratio (6 active: 2 control) to the active 
arm for receiving BGB-DXP593 or to the control arm for receiving the same volume of placebo (ie, 
normal saline), respectively. The sentinel dosing will be adopted for each dose level. In the other 
words, 2 eligible subjects will be randomized at a 1:1 ratio (1 active: 1 control) to receive 
BGB-DXP593 or placebo on Day 1; and the remaining subjects will be randomized at a 5:1 ratio 
(5 active: 1 control) to receive BGB-DXP593 or placebo at least 48 hours later, provided satisfactory 
safety and tolerability is demonstrated for the first 2 subjects randomized and dosed at the dose level. 
Dose Level 
Number of Subjects b 
Active Arm (BGB-DXP593) 
Control Arm (Normal Saline) 
A – 10 mg/kg 
6 
2 
B – 30 mg/kg 
6 
2 
C a  
6 
2 
Abbreviation: PK, pharmacokinetic. 
a Besides the 2 planned dose levels, one higher dose level will be allowed. The higher dose level will be triggered 
based on the review of PK data from the first 2 dose levels. 
b Enrollment up to 30 subjects is permitted if additional subjects are necessary for safety or PK evaluations. 
Subjects are expected to be available for follow-up visits until Day 113 of the study. Subjects will be 
replaced if they cannot complete the infusion. Subjects may be replaced if they discontinue from the 
study before Day 29. 
The administration of the study drug and the enrollment of new subjects will pause for the dose level, if 
any of the following events occurs:  
• 
One or more ≥ Grade 4 TEAEs or treatment-emergent SAEs related to study drug as 
assessed by the investigator in any subject or 
• 
Grade 3 TEAEs related to study drug as assessed by the investigator in 2 or more subjects 
at the same dose level. 
The Safety Monitoring Committee (SMC) will review the safety and laboratory data at each dose level. 
The SMC may recommend keeping the current enrollment plan, opening a repeated cohort at the same 
dose level, de-escalating to a lower dose level, or terminating the study. For the scenarios of repeated 
dose level and lower dose level, the number of subjects and randomization ratio will be the same as 
planned dose levels.  
If a repeated cohort evaluation of the same dose level confirms the AE profile previously observed at 
the dose level, no higher dose level will be tested in this study. 
 
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Study Assessments: 
Subjects will be monitored for safety, tolerability, PK, and immunogenicity of BGB-DXP593 
throughout the study. 
Assessments of safety will include adverse events (AEs), SAEs, clinical laboratory tests, physical 
examinations, vital signs, and ECGs. Adverse events will be graded for severity per the current version 
of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) 
version 5.0. A SMC will periodically monitor safety data.  
PK and ADA sampling will be collected at specific intervals from Day 1 to Day 113. 
Key Eligibility Criteria 
Subjects to be included in this study will be adults between 18 and 60 years of age at the time of 
informed consent and in good general health.   
Test Product, Dose, and Mode of Administration 
BGB-DXP593 will be administered intravenously at a dose of 10 mg/kg or 30 mg/kg for 30-60 
minutes. 
Reference Therapy, Dose, and Mode of Administration 
Normal saline (ie, solution of 0.9% sodium chloride) will be administered intravenously for 30-60 
minutes. 
Statistical Methods 
The focus of this first-in-human study is to evaluate the safety, tolerability, PK and immunogenicity of 
BGB-DXP593. No formal statistical hypotheses will be tested. 
Analysis Sets: 
The Safety Analysis Set will include all the subjects who received the study drug. 
The PK Analysis Set will include all the subjects who received the study drug and had any measurable 
concentration of study drug. 
The ADA Analysis Set will include all the subjects who received the study drug and in whom both 
baseline ADA and at least 1 postbaseline ADA results are available. 
Safety Analyses: 
Adverse events, ECGs, vital signs, and laboratory data will be reviewed and summarized on an 
ongoing basis during the study to evaluate the safety of subjects. Descriptive statistics will be used to 
analyze all safety data.  
A TEAE is defined as an AE that had an onset date or a worsening in severity from baseline on or after 
the administration of study drug and up to 30 days after the dose of study drug. Only those AEs that 
were treatment emergent will be included in the summary tables. The incidence of TEAEs will be 
reported as the number (percentage) of subjects with TEAEs by system organ class and preferred term. 
The treatment-emergent SAEs and treatment-related TEAEs will also be summarized. All AEs, 
treatment emergent or otherwise, will be presented in subject data listings. 
Changes from baseline for the ECG parameters and vital signs will be summarized by visit and dose 
level. 
Abnormal laboratory values will be flagged and identified as those outside (above or below) the normal 
range. Laboratory parameters and their changes from baseline will be summarized by visit and dose 
level. 
Pharmacokinetic Analyses: 
Noncompartmental analysis will be carried out for BGB-DXP593 serum concentrations.  
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Parameters, such as Cmax, tmax, t1/2, AUCt, AUCinf, AUC0-29, CL, and Vz (as appropriate for data 
collected), may be derived and summarized with descriptive statistics (sample size, mean, standard 
deviation, coefficient of variance, median, minimum, maximum, geometric mean, geometric 
coefficient of variance). Individual serum concentration-versus-time data will be tabulated and plotted 
by dose level. Additional PK analyses may be conducted as appropriate. 
Immunogenicity Analyses: 
The immunogenicity results will be summarized using descriptive statistics by the number and 
percentage of subjects who develop detectable ADAs. The incidence of positive and neutralizing 
ADAs will be reported for evaluable subjects. The effect of immunogenicity on PK, and safety may be 
evaluated if data allow. 
Sample Size Consideration: 
A sample size of 8 subjects at each dose level (6 active and 2 control) totaling up to 30 subjects 
(including possible replacement) is not based on any statistical considerations.  The sample size is 
based on the clinical consideration to provide safety and tolerability information as well as 
pharmacological considerations with the need to minimize exposure of healthy subjects at each dose 
level.  No formal inferential statistics will be applied to the safety or PK data. 
 
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LIST OF ABBREVIATIONS AND TERMS 
Abbreviation 
Definition 
ACE2 
angiotensin-converting enzyme 2 
ADA 
antidrug antibody 
AE 
adverse event 
AUC 
area under the concentration-time curve 
BGB-DXP593 
code name for monoclonal antibody BGB-DXP593, also named DXP593, 
BD-368-2, and WBP2281 
CL 
clearance 
Cmax 
maximum observed concentration 
COVID-19 
Coronavirus Disease 2019 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EOS 
End-of-Study 
GCP 
Good Clinical Practice 
ICF 
informed consent form 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
MedDRA® 
Medical Dictionary for Regulatory Activities 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
PK 
pharmacokinetic 
PT 
preferred term 
RBD 
receptor-binding domain 
SAE 
serious adverse event 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SMC 
Safety Monitoring Committee 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
t1/2 
terminal half-life 
tmax 
time to maximum observed concentration  
VZ 
volume of distribution 
 
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1. 
INTRODUCTION AND RATIONALES 
1.1. 
Introduction 
Coronavirus Disease 2019 (COVID-19) is an acute respiratory infection caused by a new strain 
of coronavirus: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Zhou P et al 
2020). As of July 2020, over 16 million confirmed cases of COVID-19 worldwide have been 
reported to World Health Organization. COVID-19 is threatening the global public health, and 
the ongoing spread of COVID-19, which has resulted in a worldwide pandemic, demands 
effective interventions against SARS-CoV-2 infections. Unfortunately, there is no vaccine and 
no prescription drug regimen which has demonstrated significant efficacy in the treatment of 
COVID-19 patients in clinical studies so far (Jean et al 2020).  
Currently, several strategies are used in the clinic or are under development, such as 
viral-targeting therapeutics and host-targeting agents (such as anti-interleukin 6 antibodies, and 
glucocorticoids) for the treatment of COVID-19. Convalescent plasma therapy has been used to 
treat COVID-19 by providing passive immune responses to the viral infection. However, the 
outcomes of passive plasma therapy are unpredictable due to the variability of sera from different 
patients (Zhou GY et al 2020). Convalescent plasma therapy is also associated with other risks, 
such as transfusion-related acute lung injury, transfusion-related overload, or 
transfusion-transmitted infection (Sullivan et al 2020). 
Neutralizing monoclonal antibodies (mAbs), generated from the plasma from convalescent 
patients, provide a more specific immune response. In addition, the antibodies with a high 
affinity to the virus can be selected. No clinical studies with SARS-CoV-2-specific neutralizing 
mAbs have been completed to date, therefore, neutralizing antibodies that effectively block virus 
entry into host cells are urgently needed (Cao et al 2020). 
1.2. 
BGB-DXP593 as a SARS-CoV-2 Neutralizing Monoclonal Antibody 
BGB-DXP593 (also named DXP593, BD-368-2, and WBP2281) is a highly potent neutralizing 
mAb identified by high-throughput single-cell sequencing of convalescent patients’ B-cells. 
BGB-DXP593 binds to the S protein receptor-binding domain (RBD) of SARS-CoV-2 with high 
specificity and affinity, preventing the virus from entering cells.   
1.2.1. 
Summary of Relevant Nonclinical Data with BGB-DXP593 
1.2.1.1. 
Pharmacology 
BGB-DXP593 binds to the S protein RBD of SARS-CoV-2 with high specificity and affinity, as 
demonstrated by target-binding assays and surface plasmon resonance characterization 
(equilibrium dissociation constant [KD] = 0.824 nM). BGB-DXP593 efficiently blocks the 
binding of RBD to angiotensin-converting enzyme 2 (ACE2) as its receptor with a concentration 
for 50% inhibition of maximal activity (IC50) of 0.81 nM in a competition enzyme-linked 
immunosorbent assay.  
The crystal structure of BGB-DXP593 fragment antigen-binding (Fab) in complex with RBD 
suggests that BGB-DXP593 would interfere with the interaction between RBD and ACE2. 
 
 
 
 
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 In addition, the structure also suggests that 
BGB-DXP593 would clash with both protomers in the ACE2 dimer.  
In cell-based assays, BGB-DXP593 potently inhibits SARS-CoV-2 infections in both 
pseudovirus and authentic virus systems with IC50 of 8 pM (0.0012 µg/mL) and 0.1 nM 
(0.015 µg/mL), IC99 of 0.6 nM (0.09 µg/mL) and 1.08 nM (0.162 µg/mL), respectively. 
BGB-DXP593 has wild-type immunoglobulin G1 (IgG1) fragment crystallizable region (Fc), 
which exhibit similar binding profile as regular IgG1 antibody in terms of binding to Fc γ 
receptors (FcγRs) and Complement 1q (C1q), suggesting competent functions of antibody 
effector.  
The neutralization efficacy of BGB-DXP593 against SARS-CoV-2 was assessed in two different 
models: human ACE2 (hACE2)-transgenic mice model and hamster (Mesocricetus auratus) 
model. The in vivo experiments exhibited that BGB-DXP593 could provide strong therapeutic 
efficacy and prophylactic protection against SARS-CoV-2 in both models. 
In hACE2 transgenic mice, 20 mg/kg BGB-DXP593 efficiently prevented SARS-CoV-2 virus 
from infecting lung tissues to undetectable levels in the prophylactic model of treatment, where 
BGB-DXP593 was injected 24 hours before the virus infection. Consistent with that, the body 
weights of the treated mice remained stasis while that of the control mice dropped by > 5% at 
5 days post infection. Similarly, BGB-DXP593 reduced the virus load by over 1000 folds in the 
therapeutic model of treatment (Cao et al 2020), where BGB-DXP593 was injected 2 hours after 
the infection. And the body weights remained unchanged over a course of 5 days, comparable to 
those in the prophylactic model of treatment, suggesting that BGB-DXP593 maintained the 
fitness of the infected mice. 
In the hamster therapeutic model of treatment, BGB-DXP593 injection led to dose-dependent 
lung viral reduction at 7 days post infection, with the best response observed with the highest 
tested dose group (ie, 20 mg/kg). All dose groups showed improved body weight loss comparing 
with the control group. BGB-DXP593 (20 mg/kg) also demonstrated preventive effect in hamster 
model when injected 1 day or 3 days before infection, while the earlier injection (ie, 1 day before 
infection) achieved superior viral load reduction and body weight maintenance. 
Please refer to the BGB-DXP593 Investigator’s Brochure for additional details regarding 
nonclinical studies of BGB-DXP593. 
1.2.1.2. 
Toxicology 
The toxicity and toxicokinetic profile of BGB-DXP593 was characterized in a 14-day 
repeat-dose toxicology study followed by a 28-day recovery in cynomolgus monkeys via 
intravenous infusion. The study for tissue cross-reactivity was evaluated in the normal frozen 
tissues from both cynomolgus monkeys and humans. The study for cytokine release responses 
was evaluated using human peripheral blood mononuclear cells (PBMCs).  
All the data collection and analyses have been completed in these studies except for the recovery 
phase data and antidrug antibody (ADA) results in the 14-day repeat-dose toxicity study. Based 
on the available data, the missing information is not considered to have an impact on the toxicity 
results and data interpretation. The 14-day repeat-dose toxicity study was conducted in 
cynomolgus monkeys at the doses of 30 mg/kg, 100 mg/kg, or 300 mg/kg, no mortality or 
morbidity was observed throughout the study; no treatment-related findings or changes were 
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observed, which included clinical observations, body weights, body temperature, ophthalmology, 
hematology, coagulation, serum chemistry, urinalysis, cytokines, gross lesions, organ weights 
and histopathology; no treatment-related changes in the functions of cardiovascular, respiratory, 
or central nervous systems were observed.  
The systemic exposure, which was evaluated by area under the concentration-time curve (AUC) 
from time zero to the 169.5 hours (AUC0-169.5h) and maximum observed concentration (Cmax), 
appeared to increase dose proportionally without apparent sex differences. No obvious drug 
accumulation or changes were found after weekly repeated doses. The no observed adverse 
effect level (NOAEL) is considered as 300 mg/kg in this study based on the available data, 
which was approximately 30-fold of the proposed first in human dose level (10 mg/kg) and 
10-fold of the proposed highest human dose level (30 mg/kg) based on body weights. 
In the study for tissue cross-reactivity, no specific binding of BGB-DXP593 was detected in 
either normal cynomolgus monkey or human tissues with the immunohistochemical method. No 
apparent BGB-DXP593 specific cytokine releases were detected in human PBMCs. 
Please refer to the BGB-DXP593 Investigator’s Brochure for more detailed information on the 
toxicology of BGB-DXP593. 
1.2.2. 
Summary of Relevant Clinical Experience with BGB-DXP593 
This is the first-in-human study of BGB-DXP593. No clinical data are available. 
1.3. 
Study Rationale 
1.3.1. 
Rationale for Matching Placebo as the Comparator 
In this study, normal saline (ie, solution of 0.9% sodium chloride) will be used as placebo. The 
volume of normal saline will be identical to the volume of BGB-DXP593. A placebo is being 
used to preserve the scientific integrity of the study and reduce any potential observational or 
performance bias.  
1.3.2. 
Rationale for BGB-DXP593 Starting Dose 
1.3.2.1. 
Allometric Scaling for Human Pharmacokinetics Projection 
Serum concentration-time profiles from 36 cynomolgus monkeys that received either a single 
dose of BGB-DXP593 at 10 mg/kg or repeated doses of BGB-DXP593 at 30 mg/kg, 100 mg/kg, 
or 300 mg/kg once every 2 weeks for 2 doses (Section 1.2.1.2) were used in a population PK 
analysis with NONMEM® Version 7.3 (ICON plc; Dublin, Ireland). 
A 2-compartment model with first-order elimination described the PK data well. Between animal 
variability was estimated for clearance (CL) and volume of distribution (Vz). A proportional 
error model was used. Human PK parameters were obtained by scaling respective cynomolgus 
monkey PK parameters multiplied by the ratio of body weight (human to monkey) and taken to 
the power of 0.75 for clearance and intercompartmental clearance and 1.0 for the central and 
peripheral compartment volumes (Mahmood and Balian 1999).  
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The serum concentration-time profiles in humans for BGB-DXP593 were simulated using 
software R Version 3.4.4 (Figure 1). The cynomolgus monkey PK parameters and projected 
human PK parameters are shown in Table 1. 
Figure 1: 
Simulated BGB-DXP593 Serum Lung (Assuming 1% Biodistribution) 
Concentration-Time Profiles in Humans 
 
Abbreviation: IC99, concentration of BGB-DXP593 required to achieve 99% inhibition of host cell infection in vitro 
in an authentic virus neutralization assay  
Notes: More details on the IC99 results are provided in Section 1.2.1.1. 
The solid lines represent for projected serum concentrations. The dashed lines represent for projected lung 
concentrations assuming 1% biodistribution. Please refer to the BGB-DXP593 Investigator’s Brochure for more 
detailed information on assuming 1% biodistribution. 
Table 1: 
BGB-DXP593 Population PK Parameter Estimates in Cynomolgus Monkeys 
and Projected PK Parameters in Humans 
Parameter (units) 
 
Cynomolgus Monkey 
Human 
Projection 
Estimate 
%RSE 
CL (L/hr) 
0.00068 
4.9 
0.0075 
Vc (L) 
0.121 
3.9 
2.96 
Q (L/hr) 
0.00299 
7.5 
0.033 
Vp (L) 
0.0984 
3.8 
2.41 
IIV CL (%) 
26.9 
14.6 
NA 
IIV Vc (%) 
24.1 
13.5 
NA 
Residual variability (%) 
14.2 
5.1 
NA 
Abbreviations: CL, clearance; hr, hour; IIV, inter-individual variability; NA, not applicable; PK, pharmacokinetic; 
Q, intercompartmental clearance; RSE, relative standard error; Vc, volume of central compartment; Vp, volume of 
peripheral compartment. 
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1.3.2.2. 
Recommendation of the First-in-Human Dose of BGB-DXP593 in Healthy 
Subjects 
A single dose of BGB-DXP593 at 10 mg/kg as the starting dose level is proposed in this 
first-in-human study for BGB-DXP593. The selection of this starting dose level was based on the 
NOAEL approach and supported by safety margins as described below. 
Based on the toxicology evaluation in a 14-day repeat-dose study in cynomolgus monkeys, the 
NOAEL was determined to be 300 mg/kg (Section 1.2.1.2). Applying a safety factor of 10, the 
maximum recommended starting dose (MRSD) is estimated as 30 mg/kg (body-weight based) 
(FDA CDER 2005). The proposed starting dose level of 10 mg/kg is 3 times lower than the 
MRSD. 
In addition, based on the AUC from time zero to infinity (AUCinf) and Cmax after the second dose 
at 300 mg/kg (ie, NOAEL in the toxicity study) in cynomolgus monkeys, the projected safety 
margins at the proposed starting dose of 10 mg/kg are 15.1 and 33.2, respectively (Table 2), 
which reflects favorably on the safety profile of BGB-DXP593. 
Please refer to the BGB-DXP593 Investigator’s Brochure for more detailed information on 
projected human concentrations. 
Table 2: 
Projected Safety Margins at Proposed Doses in Humans 
Safety Margin 
BGB-DXP593 Dose (mg/kg) 
10 
30 
60 
AUC based 
Cmax based 
Abbreviations: AUC, area under concentration-time curve; Cmax, maximum observed concentration  
Note: The proposed dose levels are 10 mg/kg and 30 mg/kg, safety margins to 60 mg/kg dose are provided for 
reference. 
1.3.3. 
Rationale for Pharmacokinetic Sampling 
The sampling schedule that follows the single dose of BGB-DXP593 is designed to capture data 
at a sufficient number of timepoints to provide a detailed profile of the concentration-time curve, 
including Cmax, time to maximum observed concentration (tmax), AUC from time zero to the time 
of the last quantifiable concentration (AUCt), AUCinf, AUC from time zero to Day 29 (AUC0-29), 
terminal half-life (t1/2), CL, and Vz. 
1.4. 
Benefit-Risk Assessment 
This is a first-in-human study and the side effects of BGB-DXP593 in humans are unknown. 
The healthy subjects in this study will not receive any health benefit from participating in the 
study other than an assessment of their medical status.  
The subjects might have some discomfort from blood collection and other study procedures. 
Other than that, the risks of study participation include possible adverse reactions associated with 
BGB-DXP593 such as infusion-related reactions.  However, since BGB-DXP593 is a human 
protein selected from recovered COVID-19 patients, it is unlikely to have any pharmacodynamic 
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effect in healthy subjects. Therefore, the risks are generally low under the current safety 
monitoring planned for this study.  
To further minimize the risk to the subjects, the method of sentinel dosing will be adopted for 
this study and each healthy subject in the study will receive only a single dose of study drug. 
1.5. 
Study Conduct 
This study will be conducted in compliance with the protocol approved by the Institutional 
Review Board (IRB) or Independent Ethics Committee (IEC) and in accordance with Good 
Clinical Practice (GCP) standards. 
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2. 
STUDY OBJECTIVES AND STUDY ENDPOINTS 
2.1. 
Study Objectives 
2.1.1. 
Primary Objective 
• To investigate the safety and tolerability of BGB-DXP593 administered intravenously 
as a single dose in healthy subjects 
2.1.2. 
Secondary Objectives 
• To characterize the pharmacokinetic (PK) profile of BGB-DXP593 administered 
intravenously as a single dose at each dose level in healthy subjects 
• To evaluate the potential immunogenicity of BGB-DXP593 administered 
intravenously as a single dose at each dose level in healthy subjects   
2.2. 
Study Endpoints 
2.2.1. 
Primary Endpoint 
• Incidence and severity of treatment-emergent adverse events (TEAEs) and 
treatment-emergent serious adverse events (SAEs) 
2.2.2. 
Secondary Endpoints 
• Changes in vital signs and 12-lead electrocardiogram (ECG) parameters from 
baseline 
• Incidence and magnitude of clinical laboratory abnormalities 
• Characterize PK concentration-time profile and PK parameters for BGB-DXP593: 
Cmax, AUCt, AUCinf, AUC0-29, tmax, t1/2, CL, and Vz as appropriate 
• Clinical immunogenicity of BGB-DXP593 evaluated through the detection of ADA 
over time 
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3. 
STUDY DESIGN 
3.1. 
Summary of Study Design 
This is a first-in-human, randomized, double-blind, placebo-controlled, single dose escalation 
study to investigate the safety, tolerability, PK, and immunogenicity of BGB-DXP593 in healthy 
subjects.  
After providing written informed consent, subjects will complete all the screening assessments. 
After being confirmed as eligible, subjects will be sequentially enrolled for different dose levels. 
Two dose levels are planned for eligible subjects to receive a single intravenous dose of study 
drug (ie, BGB-DXP593 or placebo) at 10 mg/kg or 30 mg/kg, respectively. Another higher dose 
level will be allowed for dose escalation.  
Enrollment will begin at the 10 mg/kg dose level. Escalation to the next dose level will occur 
7 days after the last subject at the current dose level has received the study drug, and the safety, 
laboratory data have been reviewed.  
At each dose level, eligible subjects will be randomized at a 3:1 ratio (6 active: 2 control) to the 
active arm for receiving BGB-DXP593 or to the control arm for receiving the same volume of 
placebo (ie, normal saline), respectively.  
The sentinel dosing will be adopted for each dose level. In the other words, 2 eligible subjects 
will be randomized at a 1:1 ratio (1 active: 1 control) to receive BGB-DXP593 or placebo on 
Day 1; and the remaining subjects will be randomized at a 5:1 ratio (5 active: 1 control) to 
receive BGB-DXP593 or placebo at least 48 hours later, provided satisfactory safety and 
tolerability is demonstrated for the first 2 subjects randomized and dosed at the dose level. 
The planned dose levels and number of subjects are provided in Table 3. Up to 30 subjects 
(including possible replacement) will be enrolled in the study, which will be conducted in 
1 center in Australia.  
Subjects are expected to be available for follow-up visits until Day 113 of the study. Subjects 
will be replaced if they cannot complete the infusion. Subjects may be replaced if they 
discontinue from the study before Day 29. 
Table 3: 
Planned Dose Levels and Number of Subjects 
Dose Level 
Number of Subjects b 
Active Arm (BGB-DXP593) 
Control Arm (Normal Saline) 
A – 10 mg/kg 
6 
2 
B – 30 mg/kg 
6 
2 
C a 
6 
2 
Abbreviation: PK, pharmacokinetic. 
a Besides the 2 planned dose levels, one higher dose level will be allowed. The higher dose level will be triggered 
based on the review of PK data from the first 2 dose levels (see Section 3.2.2.2). 
b Enrollment up to 30 subjects is permitted if additional subjects are necessary for safety or PK evaluations.  
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Study Assessments 
Subjects will be monitored for safety, tolerability, PK and immunogenicity of BGB-DXP593 
throughout the study. 
Assessments of safety will include adverse events (AEs), SAEs, clinical laboratory tests, 
physical examinations, vital signs, and ECGs. A Safety Monitoring Committee (SMC) will 
periodically monitor safety data. 
Adverse events will be graded for severity per the current version of the National Cancer 
Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Refer to 
Section 9 for additional and specific information regarding AE monitoring and reporting. 
PK and ADA sampling will be collected at specific intervals from Day 1 to Day 113 
(Appendix 3). 
Study procedures and assessments are further detailed in Section 7 and Section 8, respectively, 
and the Schedule of Assessments can be found in Appendix 1. Specific details regarding dose 
escalation are described in the following sections. 
3.2. 
Details of Dose Escalation 
3.2.1. 
Starting Dose and Dose Escalation Approach 
Dose escalation will occur sequentially in increasing dose levels of study drug. Each dose level 
of study drug evaluated may be referred to as a cohort or dose level. This is a single dose 
escalation study, therefore, only 1 dose of BGB-DXP593 or placebo will be administered to each 
subject. 
The starting dose level will be 10 mg/kg. This dose level was chosen based on an overall 
assessment of toxicology data in cynomolgus monkeys (more details are provided in Section 
1.3.2).  
Two ascending dose levels for study drug at single doses of 10 mg/kg and 30 mg/kg, are 
included in the study. Besides the 2 planned dose levels, one higher dose level will be allowed 
(see details in Section 3.2.2). The projected safety margins at the proposed dose levels reflect 
favorably on the safety profile of BGB-DXP593 and show that a dose up to 60 mg/kg is expected 
to provide adequate (> 2 fold) safety margins (Table 2). 
3.2.2. 
Rules for Dose Escalation 
The study design allows a gradual dose escalation with intensive safety monitoring to ensure the 
safety of the subjects. In this single dose escalation study with healthy subjects, the maximum 
factor for the first dose escalation step will be 4, the maximum factor for the following potential 
dose escalation step will be 3.  
3.2.2.1. 
Escalation From Dose Level A to Dose Level B 
Dose escalation will occur in sequential order after reviewing at least 7 days of safety and 
laboratory data by the SMC and in the absence of meeting any prespecified pausing criteria 
(more details are provided in Section 3.3). 
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An appropriate interval (at least 7 days) between dose levels will require a timely review and 
evaluation of safety data (eg, AE profile, vital signs, 12-lead ECG, cardiac telemetry, and clinical 
laboratory safety tests) prior to proceeding to a higher dose level.  
The data will be reviewed by the SMC (Section 11.1) who will decide on the next dose level. 
The data from all the subjects in the previous dose level will be reviewed. Proceeding to the next 
higher dose level will only occur if the previous dose level was deemed by the SMC to be safe 
and well tolerated. 
Following the review of data from subjects under a dose level, the timing of assessments and/or 
blood samples may be adjusted for subsequent dose level(s). Additional assessments or sampling 
times may be added or removed if indicated by the data; however, the maximum blood volume 
taken from each subject will not exceed 450 mL. 
3.2.2.2. 
Potential Escalation From Dose Level B to Dose Level C 
There is an option to explore a third dose level that is higher than 30 mg/kg in this study. The 
conduct of the third dose level will be triggered based on the review of PK data from the first 2 
dose levels.  
Pharmacokinetic data from a minimum of 3 subjects per dose level, up to Day 29, will be 
evaluated to ensure that the PK of BGB-DXP593 is approximately dose proportional and in line 
with the predicted concentrations and safety margins. The predicted exposure for Dose Level C, 
based on PK data from the first 2 dose levels, will not exceed the cynomolgus monkey exposure 
based on Cmax and combined AUC of the repeat doses at the NOAEL (ie, 300 mg/kg). The data 
will be reviewed by the SMC (Section 11.1).  
3.3. 
Criteria for Pausing Drug Administration and New Enrollment 
The SMC will review the safety and laboratory data at each dose level. If an increased risk for 
the subjects is suspected during the study, the SMC will recommend to immediately suspend the 
recruiting of additional participants.  
The administration of the study drug and the enrollment of new subjects will pause for the dose 
level, if any of the following events occurs:  
• One or more ≥ Grade 4 TEAEs or treatment-emergent SAEs related to study drug as 
assessed by the investigator in any subject or 
• Grade 3 TEAEs related to study drug as assessed by the investigator in 2 or more 
subjects at the same dose level. 
The SMC may recommend keeping the current enrollment plan, opening a repeated cohort at the 
same dose level, de-escalating to a lower dose level, or terminating the study. For the scenarios 
of repeated dose level and lower dose level, the number of subjects and randomization ratio will 
be the same as planned dose levels. 
If a repeated cohort evaluation of the same dose level confirms the AE profile previously 
observed at the dose level, no higher dose level will be tested in this study. 
 
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4. 
SELECTION OF STUDY POPULATION 
The specific eligibility criteria for the selection of subjects are provided in Section 4.1 and 
Section 4.2.  The sponsor will not grant any eligibility waivers. 
4.1. 
Inclusion Criteria 
Each subject must meet all the following inclusion criteria to be considered eligible for 
participation in this study: 
1. Male and female subjects, 18 to 60 years of age inclusive, at the time of signing the 
informed consent 
2. Subjects are in good general health as determined by the investigator or medically 
qualified designee, based on a medical evaluation including medical history, physical 
examination, laboratory tests and cardiac monitoring 
3. Body weight ≥ 50 kg and body mass index (BMI) within the range 18 to 32 kg/m2 
(inclusive) 
Note: BMI = weight [kg] / (height [m])2 
4. Negative serum IgG to the SARS-CoV-2 
5. Negative for COVID-19 based on the nasopharyngeal or oropharyngeal swab with the 
method of real-time reverse transcription-polymerase chain reaction (rRT-PCR) 
6. Female subjects of childbearing potential must be willing to use a highly effective 
method of birth control (see Appendix 5) from the time of study enrollment until 
4 months after the single dose of study drug. 
7. Male subjects with female partners of childbearing potential must be willing to use a 
highly effective method of birth control (see Appendix 5) from the time of study 
enrollment until 4 months after the single dose of study drug. 
8. Able to provide written informed consent and can understand and agree to comply with 
the requirements of the study and the schedule of assessments 
4.2. 
Exclusion Criteria 
Subjects who meet any of the following criteria will be excluded from this study: 
Medical Histories or Conditions 
1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, 
endocrinological, hematological, or neurological disorders capable of significantly 
altering the absorption, metabolism, or elimination of drugs, constituting a risk to the 
subject when taking the study drug; or interfering with the interpretation of data 
2. Systolic blood pressure > 150 mmHg at screening  
3. Any malignancy within the past 5 years except for basal cell or squamous epithelial 
carcinomas of the skin that have been resected with no evidence of metastatic disease for 
3 years 
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4. Any history of a severe allergic reaction prior to enrollment that has a reasonable risk of 
recurrence during the study 
5. Have a medical history of SARS infection 
6. Any acute fever disease or infections 
7. Any chronic or clinically significant medical condition that, in the opinion of the 
investigator, would jeopardize the safety or rights of the subject, including but not limited 
to: diabetes mellitus type I, chronic hepatitis; or clinically significant forms of: drug or 
alcohol abuse, asthma (except for childhood asthma), autoimmune disease, psychiatric 
disorders, or heart disease 
8. Platelet disorder or other bleeding disorder may cause injection contraindication 
9. Alanine aminotransferase and/or aspartate aminotransferase > 1.5 x upper limit of normal 
(ULN)  
10. Bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is 
fractionated and direct bilirubin < 35%) 
11. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with 
the exception of Gilbert's syndrome or asymptomatic gallstones) 
12. Average Fridericia’s formula (QTcF) > 450 msec (based on triplicate ECGs) 
• NOTE A: The QTc is the QT interval corrected for heart rate according to QTcF, 
and/or another method. It is either machine-read or manually over-read. 
• NOTE B: The specific formula used to determine eligibility or discontinuation for an 
individual participant should be determined prior to initiation of the study. In other 
words, several different formulas cannot be used to calculate the QTc for an 
individual participant and then the lowest QTc value used to include or discontinue 
the participant. 
Prior/Concomitant Therapy 
13. Previous receipt of a licensed or investigational biologic agent (such as, monoclonal 
antibodies) within 3 months or 5 half-lives (whichever is longer) prior to the 
randomization 
14. Previous receipt of a licensed or investigational nonbiologic agent (such as, those derived 
from chemical synthesis) within 1 month or 5 half-lives (whichever is longer) prior to the 
randomization 
15. Past or intended use of over-the-counter or prescription medication, including herbal 
medications, within 28 days prior to the randomization. Use of paracetamol, ibuprofen, 
and/or vitamins at the recommended dose will be allowed at the investigator’s discretion 
within 28 days prior to the randomization. 
Prior/Concurrent Clinical Study Experience 
16. Participation in ≥ 4 clinical studies within 12 months prior to the randomization 
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Diagnostic Assessments 
17. Positive human immunodeficiency virus (HIV) antibody test 
18. Presence of hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody 
(HBcAb) at screening or within 3 months prior to the randomization 
19. Positive hepatitis C antibody test result at screening or within 3 months prior to the 
randomization 
NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can 
be enrolled if a confirmatory negative hepatitis C RNA test is obtained. 
20. Positive hepatitis C RNA test result at screening or within 3 months prior to the 
randomization 
NOTE: Test is optional and participants with negative hepatitis C antibody test are not 
required to also undergo hepatitis C RNA testing. 
21. Positive pre-study alcohol/drugs screen 
Other Exclusions 
22. Immediate family history of seizures, epilepsy, brain or mental disease at the 
investigator’s discretion 
23. The total volume of blood loss > 500 mL within 3 months prior to the randomization 
24. Sensitivity to any of the study drug or components thereof, or other allergy that, in the 
opinion of the investigator or medical monitor, contraindicates participation in the study 
25. Heavy smokers who have ≥ 15 cigarettes per day 
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5. 
STUDY TREATMENT 
5.1. 
Formulation, Packaging, and Handling 
5.1.1. 
BGB-DXP593 
BGB-DXP593 is a neutralizing mAb formulated for intravenous injection in a single-use vial 
(United States Pharmacopeia [USP] type I), containing a total of 300 mg of antibody in 10 mL of 
buffered isotonic solution.  BGB-DXP593 has been aseptically filled in single-use vials with a 
rubber stopper capped by an aluminum flip-off seal. Five single-use vials are packaged into each 
carton box. The contents of the label from vials and carton boxes will be in accordance with all 
applicable local regulatory requirements. 
The study drug will be dispatched to the study center only after receipt of the required documents 
in accordance with applicable regulatory requirements and the sponsor’s procedures. The 
unblinded pharmacist(s) or designated personnel are responsible for maintaining the drug supply 
inventory and acknowledging receipt of all study drug shipments. The study drug must be stored 
in a secure area, with access limited to the authorized study center personnel and kept under 
physical conditions that are consistent with study drug-specific requirements. BGB-DXP593 
must be stored at temperatures between 2 oC and 8oC and protected from light.   
Refer to the Pharmacy Manual for details regarding intravenous administration, accountability, 
and disposal. Please also refer to the BGB-DXP593 Investigator’s Brochure for other details 
regarding BGB-DXP593. 
5.1.2. 
Placebo 
Placebo matching BGB-DXP593 is the normal saline (ie, solution of 0.9% sodium chloride) to 
the required volume. The normal saline will be sourced and provided by the site. 
For further details, refer to the Pharmacy Manual for the matching placebo. 
5.2. 
Dosage, Administration, and Compliance 
All eligible subjects will be assigned to one of the dose levels. Each subject will receive a single 
intravenous dose of BGB-DXP593 or matching placebo for 30-60 minutes. The dose of study 
drug will be based on the subject’s actual body weight on the day of study administration.  
As a routine precaution, subjects must be monitored for at least 2 hours after the infusion of 
study drug in an area with resuscitation equipment and emergency agents. The study drug must 
not be administered concurrently with any other drug. 
For safety reasons, dose administration for the first 2 subjects randomized and dosed at each dose 
level will be monitored for at least 48 hours prior to the remaining subjects receiving the same 
dose level. 
After the starting dose of study drug, the decision to proceed to each subsequent dose level will 
be made by the SMC at 7 days after the last subject at the current dose level has received the 
study drug, and all the safety, laboratory data have been reviewed. 
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Accurate records of the study drug received, dispensed, returned, and disposed of should be 
maintained in the site’s Drug Inventory Log. Please refer to the Pharmacy Manual for details 
regarding study drug management, drug preparation, storage, and administration. 
5.3. 
Measures to Minimize Bias: Randomization and Blinding 
Randomization 
At each dose level, eligible subjects will be randomized at a 3:1 ratio (6 active: 2 control) to 
receive BGB-DXP593 or placebo, respectively. The sentinel dosing will be adopted for each 
dose level and the randomization ratios for sentinel dosing are provided in Section 3.1. 
Site personnel will access the Interactive Response Technology (IRT) system to randomize the 
treatment assignment. A subject for replacement will receive a unique study subject number and 
will be assigned to the same treatment as the subject he/she replaces.  
Blinding 
The study is designed as double-blind for the subjects and the investigator (as well as the site 
personnel) in order to eliminate observational or performance bias. This is to avoid the 
systematic differences in assessments on the subject’s treatment (ie, BGB-DXP593 or placebo).  
The single dose of study drug will be prepared by unblinded pharmacist(s) and administered by 
blinded study nurse(s). Both the intravenous infusion of BGB-DXP593 and placebo will be 
colorless. All the follow-up evaluations will be performed by blinded clinic staff. 
At the study site, access to the treatment information for each subject is restricted to the 
unblinded pharmacist(s). Persons directly involved in the clinical conduct of the study will not 
have access to the treatment allocation prior to database lock. 
Regarding the sponsor, the database of this study will be handled as open-label, meaning that the 
study functions of the sponsor are unblinded (including the medical monitor and study team 
members from Pharmacovigilance/Drug Safety, Clinical Pharmacology, and Biostatistics with 
other members as appropriate). The objectives of the study are expected not to be affected. 
Unblinding 
1. Emergency unblinding  
In case of an emergency, the investigator has the sole responsibility for determining if the 
unblinding of a subject’s treatment assignment is warranted. Subject safety must always be the 
first consideration in making such a determination. Emergency unblinding for AEs may be 
performed through an IRT system. 
If the investigator decides that unblinding is warranted, the investigator should make every effort 
to contact the medical monitor before unblinding a subject’s treatment assignment unless this 
could delay emergency treatment of the subject. If a subject’s treatment assignment is unblinded, 
the sponsor must be notified immediately. 
2. Inadvertent unblinding  
Every effort will be made to blind both the subject and the investigator to the identity of 
BGB-DXP593 or placebo, but inadvertent unblinding of a subject may occur. If an investigator, 
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site personnel performing assessments, or subject is unblinded, the unblinding will not be the 
sufficient cause for that subject to be discontinued from study or excluded from any analyses. 
5.4. 
Incorrect Administration 
Any incorrect administration of the study drug should be noted in the subject’s medical record 
and on the appropriate electronic case report form (eCRF). 
Adverse events due to an incorrect administration of the study drug will be recorded on the AE 
eCRF. Any SAEs associated with an incorrect administration must be reported within 24 hours 
of awareness via the SAE reporting process as described in Section 9.6.2. Supportive care should 
be administered as appropriate. 
5.5. 
Dose Interruption or Modification 
There will be no dose reduction of study drug. 
A subject may temporarily interrupt their infusion of study drug or discontinue their infusion of 
study drug due to infusion-related reactions or other medical events.  
The subject should resume the study treatment within 2 hours of the infusion interruption if the 
AE is resolved or recovered to Grade 1 (whichever is more severe). If the subject is unable to 
resume the study drug within 2 hours of the infusion interruption, then the subject should be 
discontinued from the study treatment and the subject will be replaced. 
The treatment modification for infusion-related reactions is provided in Section 9.7.1. 
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6. 
PRIOR AND CONCOMITANT THERAPY 
6.1. 
Prior Therapy 
The exclusion criteria (Section 4.2) specify that: 
• subjects must not have received any licensed or investigational biologic agent (such 
as, monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) prior 
to the randomization 
• subjects must not have received any licensed or investigational nonbiologic agent 
(such as, those derived from chemical synthesis) within 1 month or 5 half-lives 
(whichever is longer) prior to the randomization 
• subjects must not have received any over-the-counter or prescription medication, 
including herbal medications, within 28 days prior to the randomization. Use of 
paracetamol, ibuprofen, and/or vitamins at the recommended dose will be allowed at 
the investigator’s discretion within 28 days prior to the randomization. 
6.2. 
Concomitant Therapy 
As the healthy subjects are enrolled in the study, concomitant therapy is not allowed during the 
study. If medical events (such as, infusion-related reactions, or severe hypersensitivity) occur 
during the study period, the subjects may receive appropriate medical treatment. The 
management of infusion-related reactions and severe hypersensitivity is provided in Section 9.7. 
All concomitant medications taken during the study will be recorded in the eCRF with indication 
and dates of administration.  
6.3. 
Potential Interactions Between BGB-DXP593 and Concomitant 
Medications 
The potential for drug-drug interaction between BGB-DXP593 and small-molecule drug 
products is very low, given that BGB-DXP593 is a monoclonal antibody.  Because 
BGB-DXP593 is expected to be degraded into amino acids and recycled into other proteins, it is 
unlikely to have an effect on drug metabolizing enzymes or transporters. 
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7. 
STUDY PERIODS, VISITS, OR PROCEDURES 
Study periods, visits, and procedures are summarized in the following subsections. The timing of 
all study procedures is provided in the Schedule of Assessments (Appendix 1). 
7.1. 
Screening Period 
Screening evaluation will be performed within 28 days before the single dose of study drug. A 
subject who agrees to participate in this study will sign the informed consent form (ICF) before 
undergoing any study-specific procedures. Refer to Section 8.1 for instructions regarding 
screening assessments. 
7.1.1. 
Informed Consent 
Voluntary, written informed consent for participation in the study must be obtained before 
performing any study-specific procedures. ICFs for enrolled subjects and for subjects who are 
screened but not enrolled will be maintained at the study site. Consent must be obtained using 
the most current version of the form approved by the IEC/IRB. 
For subjects who provide informed consent and subsequently do not meet eligibility criteria or 
withdraw consent before the single dose of study drug is administered, study site personnel 
should document the screen failure in the subject’s source documents.  The documentation 
should include demographics and medical history, the reason for screen failure, the eligibility 
criteria reviewed, procedures performed.   
7.2. 
Enrollment 
7.2.1. 
Confirmation of Eligibility 
The investigator will assess and confirm the eligibility of each subject. All screening results and 
relevant medical history must be available before eligibility can be determined. All inclusion 
criteria must be met and none of the exclusion criteria may apply. No eligibility waivers will be 
granted.  
7.2.2. 
Subject Numbering 
After obtaining informed consent, a unique subject number will be assigned to a potential study 
participant. 
7.3. 
Check-in (Day -1) 
The enrolled subjects will be admitted at least 12 hours prior to the single dose of study drug. On 
the day of admission, the screening of alcohol/drugs and safety assessment of vital signs will be 
performed. Smoking will be not allowed during the inpatient stay. 
7.4. 
Randomization  
Site personnel will access the IRT system to randomize the treatment assignment. 
Randomization will occur after the admission on Day -1 and before the dose of study drug on 
Day 1. 
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7.5. 
Treatment (Day 1) 
The enrolled subjects will be treated as described in Section 5.2. The study procedures on Day 1 
are provided in Appendix 2. Refer to Section 7.7 for additional considerations regarding 
treatment withdrawal. 
7.6. 
Follow-up Period 
The follow-up period starts with the next day following the infusion of study drug and continues 
until Day 113 of the study. All AEs, including SAEs, will be collected as described in 
Section 9.6. 
7.6.1. 
Check-out (Day 8) 
The subjects will be discharged 7 days after the single dose of study drug. Before the discharge, 
the procedures and assessments specified in Appendix 1 should be completed. 
7.6.2. 
End-of-Study Visit 
Subjects who permanently discontinue from the study will be asked to return to the study center 
for the End-of-Study (EOS) Visit, which is required to be conducted within 7 days after the 
premature study discontinuation. The Day 113 Visit is the EOS Visit for subjects who complete 
all the previously planned study visits. 
If a subject refuses to return for the EOS Visit or is unable to do so, every effort should be made 
to contact the subject by telephone to determine their health status. 
7.6.3. 
Safety Follow-up Visit for Premature Study Discontinuation 
If a subject discontinues the study within 30 days after the dose of study drug, a Safety 
Follow-up Visit will be conducted on 30 days after the dose of study drug. If the premature 
discontinuation from study occurs within 7 days prior to the timepoint of 30 days after the dose 
of study drug, the Safety Follow-up Visit could be combined with the EOS Visit as appropriate. 
A visit window of ± 3 days will be allowed for Safety Follow-up Visit.  
7.6.4. 
Lost to Follow-up 
If attempts to contact a subject by telephone are unsuccessful, additional attempts should be 
made during the study to complete study-related assessments and record outstanding data. It may 
be possible to obtain the information from other contacts, such as referring physicians, or 
primary care providers.  
Attempts to contact should be documented in the subject’s source documents. If a subject cannot 
be contacted despite all attempts, the subject will be considered lost to follow-up. 
7.7. 
Discontinuation From Study Treatment or From the Study 
7.7.1. 
Subject Discontinuation From the Study Treatment 
Eligible subjects will receive a single dose of study drug and they have the right to discontinue 
the study drug at any time for any reason during the study treatment. In addition, the investigator 
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has the right to discontinue a subject from the study drug at any time during the study treatment. 
Subjects who discontinue the study treatment should follow the procedures and the assessments 
specified in EOS Visit (Section 7.6.2). The subject who could not complete the infusion should 
be replaced. 
The primary reason for discontinuation from the study treatment should be documented on the 
appropriate eCRF. Subjects may discontinue from the study treatment for reasons that include, 
but are not limited to, the following: 
• Withdraw of consent 
• The investigator or sponsor determines it is in the best interest of the subject 
• Significant or persistent AE(s) as described in Section 9.7. 
7.7.2. 
Subject Discontinuation From the Study 
Subjects may discontinue from the study for reasons that include, but are not limited to, the 
following: 
• Subject withdrawal of consent 
• Study termination by sponsor 
• Lost to follow-up 
• Completion of all study assessments 
• Positive for COVID-19 
Subjects may voluntarily withdraw consent from the study at any time. The subject who 
discontinues from the study before Day 29 may be replaced. 
7.8. 
End of Study 
The end of study is defined as the timepoint when the final data for a clinical study were 
collected, which is after the last subject has made the final visit to the study center.  
Alternatively, the end of study is when the sponsor decides to terminate the study. The sponsor 
has the right to terminate this study at any time. Reasons for terminating the study early include, 
but are not limited to, the following:  
• The incidence or severity of AEs in this or other studies on BGB-DXP593 indicates a 
potential health hazard to subjects 
• Overall subject enrollment is unsatisfactory 
The sponsor will notify the investigator if a decision is made to terminate the study. Should this 
be necessary, prematurely discontinued subjects must be seen for an EOS Visit as described in 
Section 7.6.2. 
The investigators may be informed of additional procedures to be followed to ensure that 
adequate consideration is given to the protection of the subject’s interests. The investigator will 
be responsible for informing IRBs/IECs of the early termination of the study. 
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8. 
STUDY ASSESSMENTS 
A table of scheduled study assessments is provided in Appendix 1. Subjects will be closely 
monitored for safety and tolerability throughout the study. All assessments will be performed on 
the day of the specified visit and documented in the medical record for each subject.  
Where applicable, the single dose of study drug will be administered only if the clinical 
assessment and laboratory test values have been reviewed and found to be acceptable per 
protocol guidelines. 
8.1. 
Screening Assessments 
Screening evaluations will be performed within 28 days before receiving the study drug. The 
screening period begins on the first day that a screening assessment is conducted. The 
investigator will assess subject eligibility according to the latest screening assessment results. 
8.1.1. 
Demographic Data, Medical History, and Prior Medications 
Demographic data will include age or year of birth, gender, and race/ethnicity.  
Medical history includes any history of clinically significant disease, surgery history, 
reproductive status (ie, no childbearing potential or childbearing potential), and smoking history. 
Prior medications include all medications (eg, prescription drugs, over-the-counter drugs, herbal 
medications) used by the subject within 28 days prior to the single study dose. 
8.2. 
Safety Assessments 
8.2.1. 
Vital Signs 
Vital signs will include measurements of body temperature (˚C), pulse rate, respiratory rate, and 
blood pressure (systolic and diastolic). Pulse rate and blood pressure will be measured while the 
subject is in a supine position after resting for 10 minutes. 
Height and weight will be measured at screening and weight will be measured again before the 
single dose of study drug on Day 1. The data of height and weight will be recorded in the eCRF. 
8.2.2. 
Physical Examinations 
During the Screening Visit, a complete physical examination will be conducted, including 
evaluations of 1) head, eyes, ears, nose, and throat, 2) cardiovascular, 3) dermatological, 
4) musculoskeletal, 5) respiratory, 6) gastrointestinal, and 7) neurological systems. Any 
abnormality identified during screening will be graded according to NCI-CTCAE version 5.0 
and recorded in the eCRF with appropriate disease/condition terms. 
At subsequent visits (and as clinically indicated), limited, symptom-directed physical 
examinations will be performed. New or worsened clinically significant abnormalities are to be 
recorded as AEs in the eCRF. Refer to Section 9.3 regarding AE definitions and reporting and 
follow-up requirements. 
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8.2.3. 
Laboratory Safety Tests 
Samples for protocol-specified clinical chemistry, hematology, urinalysis, and coagulation 
profiles will be evaluated by a local laboratory.  
Pregnancy test will be performed for female subjects of childbearing potential during the study. 
Samples for pregnancy testing will also be assessed locally. The serum pregnancy test will be 
performed at the Screening Visit, and the next serum pregnancy test will be conducted after the 
admission on Day -1 and before the dose of study drug on Day 1. Female subjects of 
childbearing potential with negative results will be eligible to receive the study drug. Afterwards, 
urine pregnancy test will be performed. A serum pregnancy test must be performed if the urine 
pregnancy test is positive or equivocal. 
See Appendix 4 for the list of clinical laboratory tests to be performed and Appendix 1 for the 
timing and frequency. Additional tests may be performed at any time during the study as deemed 
necessary by the investigator or as required by local regulations. If required by local regulations, 
clinical laboratory evaluations performed by a local (instead of a central) laboratory are 
acceptable. 
A detailed description of the procedures for sample collection, handling, storage, and shipment 
of the laboratory samples and all materials such as test tubes and labels are provided in the 
Laboratory Manual. 
8.2.4. 
Electrocardiograms 
For safety monitoring purposes, the investigator must review, sign, and date all ECG tracings. 
Paper or electronic copies of ECG tracings (per local practice) will be kept as part of the 
subject’s permanent study file at the site. 
The subject should rest in a semirecumbent or supine position for ≥ 10 minutes in the absence of 
environmental distractions that may induce changes in heart rate (eg, television, radio, 
conversation) before each ECG collection. 
At each timepoint (see Appendix 1), 3 consecutive 12-lead ECGs will be performed 
approximately 2 minutes apart to calculate heart rate and measure QT and QTcF intervals. 
8.2.5. 
Cardiac Telemetry 
The cardiac telemetry will be performed from approximately 1 hour predose to 24 hours post 
dosing. Full disclosures will be maintained as part of the subject’s source documents and will be 
reviewed in detail. 
8.2.6. 
Adverse Events 
AEs will be graded and recorded throughout the study according to NCI-CTCAE version 5.0. 
Characterization of toxicities will include severity, duration, and time to onset.  
All AEs, including SAEs, will be collected as described in Section 9.6 . 
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8.2.7. 
Serology 
The testing of HBV/HCV serology (hepatitis B surface antigen [HBsAg], hepatitis B core 
antibody [HBcAb], and HCV antibody) will be performed at screening. In the case of positive 
HCV antibody, the test of HCV RNA will be followed. 
Blood from all subjects will be collected and tested for HIV antibody at screening. Those 
subjects with negative results can be enrolled.  
Specific IgG antibodies against SARS-CoV-2 in the serum of all subjects will be measured by 
quantitative or qualitative antibody testing. Those subjects with negative results can be enrolled.  
The tests mentioned above will be performed at a local laboratory. 
8.2.8. 
Virology 
The nasopharyngeal or oropharyngeal swab will be collected during the Screening and at the 
visit on Day 29. The nasopharyngeal or oropharyngeal swab will be tested by the method of 
rRT-PCR in a local laboratory for the qualitative detection of nucleic acid from SARS-CoV-2 in 
upper respiratory specimens. During the screening, those subjects who have negative results can 
be enrolled.  
If any subject has positive or suspected result during the study, the subject will be discontinued 
from the study and treated by following local practice. If the subject is unable to complete the 
EOS Visit, please see the procedures in Section 7.6.2 and Section 7.6.4. 
8.3. 
Pharmacokinetic Assessment and Antidrug Antibody Testing 
Blood will be collected to characterize the PK profile of BGB-DXP593 using validated 
immunoassays. Blood samples will be collected for characterization of ADA. Validated 
screening and confirmatory assays will be employed to detect ADAs in the samples. Samples 
collected for analyses of blood concentration may also be used to evaluate safety or efficacy 
aspects related to concerns arising during or after the study. 
Blood sampling for PK and ADA will be collected at the timepoints specified in the PK and 
immunogenicity sampling schedule (Appendix 3).  
The PK and ADA assays for BGB-DXP593 will be managed through a central laboratory. Refer 
to the laboratory manual for instructions regarding sample collection, handling, labeling, storage, 
and shipping of laboratory samples. The actual time of each sample collected will be captured to 
the nearest minute in the eCRF and recorded in the database. 
8.4. 
Visit Windows 
The PK sampling schedule allows for a visit window of ± 1 day for the visits at Day 15, Day 22 
and Day 29, and a visit window of ± 2 days for the visits at Day 43, Day 57, Day 71, Day 85, and 
Day 113 (Appendix 1 and Appendix 3). All assessments will be performed on the day of the 
specified visit. 
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8.5. 
Unscheduled Visits 
Unscheduled visits may be performed at any time at the subject’s or investigator’s request if 
there are any safety concerns.  The date and reason for the unscheduled visit must be recorded in 
the source documentation.   
If an unscheduled visit is necessary to assess toxicity, then diagnostic tests may be performed 
based on the investigator’s assessment as appropriate, and the results of these tests should be 
recorded on the unscheduled visit eCRF. 
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9. 
SAFETY MONITORING AND REPORTING 
The investigator is responsible for the monitoring and documentation of events that meet the 
criteria and definition of an AE or SAE as provided in this protocol.   
9.1. 
Risks Associated With BGB-DXP593 
This is the first-in-human study of BGB-DXP593. No clinical data are available yet and no risk 
associated with BGB-DXP593 has been identified. In the 14-day repeat-dose toxicology study, 
no apparent toxicity was observed in cynomolgus monkeys at weekly repeated doses of 
30 mg/kg, 100 mg/kg, or 300 mg/kg. 
9.2. 
General Plan to Manage Safety Concerns 
9.2.1. 
Eligibility Criteria 
Eligibility criteria were selected to guard the safety of subjects in this study. Results from the 
nonclinical toxicology data from BGB-DXP593 and nonclinical data from other SARS-CoV-2 
neutralizing mAbs were considered. Subjects with any history of a severe allergic reaction that 
has a reasonable risk of recurrence are excluded from the study. Subjects with acute fever disease 
or infection are also excluded from the study (See Section 4.2 for the full list of exclusion 
criteria). 
9.2.2. 
Safety Monitoring Plan 
Safety will be evaluated in this study through the monitoring of all AEs, defined and graded 
according to NCI-CTCAE version 5.0.  
All enrolled subjects will be evaluated clinically and with standard laboratory tests at specified 
intervals during their participation in this study. Safety evaluations will consist of medical 
interviews, recording of AEs, physical examinations, laboratory measurements (hematology, 
clinical chemistry, etc), and other assessments including those listed in Appendix 1.  
Blood samples will be drawn for determining of ADAs to BGB-DXP593 in subjects who 
received the study drug. Administration of the study drug will be performed in a setting where 
emergency medical equipment and staff who are trained to respond to medical emergencies are 
available (Section 5.2). 
As described in Section 9.6, AEs will be recorded during the study (AE from the time of single 
study dose and SAEs from the time of signing of informed consent). At the end of study, AEs 
considered related to study drug will be followed until the event has resolved to baseline or 
≤ Grade 1, the event is assessed by the investigator as stable, the subject is lost to follow-up, the 
subject withdraws consent, or it has been determined that study treatment or participation is not 
the cause of the AE. 
Investigators are instructed to report all AEs. The potential safety issues anticipated in this study, 
as well as measures intended to avoid or minimize such toxicities, are outlined in the following 
sections. 
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9.3. 
Adverse Events 
9.3.1. 
Definitions and Reporting  
An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study 
drug, whether considered related to study drug or not. 
Examples of an AE include: 
• Worsening of a chronic or intermittent pre-existing condition, including an increase in 
severity, frequency, duration, and/or has an association with a significantly worse 
outcome. 
• New condition(s) detected or diagnosed after study drug administration even though 
it may have been present before the start of the study.  
• Signs, symptoms, or the clinical sequelae of a suspected interaction.  
• Signs, symptoms, or the clinical sequelae of a suspected incorrect administration of 
either study drug or a concurrent medication.  
When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory results and diagnostics reports) relative to 
the AE or SAE. The investigator will then record all relevant information regarding an AE or 
SAE in the eCRF. However, there may be instances when copies of medical records for certain 
cases are requested by the sponsor. In these instances, all subject identifiers will be blinded on 
the copies of the medical records prior to submission to the sponsor. 
9.3.2. 
Assessment of Severity 
The investigator will assess severity for each AE and SAE reported during the study.  Adverse 
events and SAEs should be assessed and graded based upon the NCI-CTCAE version 5.0. 
Toxicities that are not specified in the NCI-CTCAE will be defined as follows: 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated  
• Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL)  
• Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL  
• Grade 4: Life-threatening consequences; urgent intervention indicated  
• Grade 5: Death related to AE  
NOTE: The terms “severe” and “serious” are not synonymous. Severity is a measure of intensity 
(for example, grade of a specific AE, mild [Grade 1], moderate [Grade 2], severe [Grade 3], or 
life-threatening [Grade 4]), whereas seriousness is classified by the criteria based on the 
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regulatory definitions.  Seriousness serves as the guide for defining regulatory reporting 
obligations from the sponsor to applicable regulatory authorities as described in Section 9.6.2.1. 
9.3.3. 
Assessment of Causality 
The investigator is obligated to assess the relationship between the study drug and the occurrence 
of each AE or SAE using best clinical judgment. Alternative causes, such as natural history of 
the underlying diseases, concomitant therapy, other risk factors, and the temporal relationship of 
the AE or SAE to the study drug should be considered and investigated.  The investigator should 
also consult the BGB-DXP593 Investigator’s Brochure in the determination of his/her 
assessment. 
There may be situations when a SAE has occurred, and the investigator has only limited 
information to include in the initial report to the sponsor. However, it is very important that the 
investigator always assesses causality for every SAE prior to transmission of the SAE report to 
the sponsor because the causality assessment is 1 of the criteria used when determining 
regulatory reporting requirements. The investigator may subsequently change his/her opinion of 
causality considering follow-up information and may amend the SAE report accordingly.  
The causality of each AE should be assessed and classified by the investigator as “related” or 
“not related." An AE is considered related if there is “a reasonable possibility” that the AE may 
have been caused by the study drug (ie, there are facts, evidence, or arguments to suggest 
possible causation). A number of factors should be considered in making this assessment, 
including: 
• Temporal relationship of the AE to the administration of study treatment/study 
procedure 
• Whether an alternative etiology has been identified 
• Mechanism of action of the study drug 
• Biological plausibility 
• An AE should be considered "related" to study drug if any of the following are met; 
otherwise the event should be assessed as "not related": 
− There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out 
− There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely 
− There is some evidence to suggest a causal relationship (eg, the AE occurred 
within a reasonable time after administration of the study drug).  However, the 
influence of other factors may have contributed to the AE (eg, the subject’s 
clinical condition or other concomitant AEs). 
9.3.4. 
Following Adverse Events and Serious Adverse Events 
After the initial AE or SAE report, the investigator is required to proactively follow each subject 
and provide further information to the sponsor on the subject’s condition. 
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All AEs and SAEs documented at a previous visit/contact and designated as ongoing will be 
reviewed at subsequent visits/contacts. 
All AEs and SAEs will be followed until resolution, the condition stabilizes or is considered 
chronic, the AE or SAE is otherwise explained, the subject is lost to follow-up, or the subject 
withdraws consent. The investigator will ensure that follow-up includes any supplemental 
investigations as may be indicated to elucidate the nature and/or causality of the AE or SAE. 
This may include additional laboratory tests or investigations, histopathological examinations, 
radiographic imaging, or consultation with other health care professionals. 
The sponsor may request that the investigator perform or arrange for the conduct of supplemental 
measurements and/or evaluations to elucidate as fully as possible the nature and/or causality of 
the AE or SAE. The investigator is obligated to assist. If a subject dies during participation in the 
study or during a recognized follow-up period, the sponsor will be provided with a copy of any 
post-mortem findings, including histopathology. 
New or updated information should be reported to the sponsor according to the SAE instructions 
provided to the site within the time frames outlined in Section 9.6.2.1. 
9.3.5. 
Laboratory Test Abnormalities 
Abnormal laboratory findings (eg, clinical chemistry, complete blood count, coagulation, or 
urinalysis) or other abnormal assessments (eg, ECGs, cardiac telemetry, or vital signs) that are 
judged by the investigator as clinically significant will be recorded as AEs or SAEs.  This 
includes clinically significant abnormal laboratory findings or other abnormal assessments that 
are present at baseline and significantly worsen during the study.  The definition of clinically 
significant is left to the judgment of the investigator.  In general, these are laboratory test 
abnormalities or other abnormal assessments that: 
• are associated with clinical signs or symptoms, or  
• require active medical intervention, or  
• lead to dose interruption or discontinuation, or 
• require close observation, more frequent follow-up assessments, or  
• further diagnostic investigation. 
9.4. 
Definition of a Serious Adverse Event 
A SAE is any untoward medical occurrence that, at any dose: 
• Results in death 
• Is life-threatening 
NOTE:  the term “life-threatening” in the definition of “serious” refers to an AE in 
which the subject was at risk of death at the time of the AE. It does not refer to an 
AE, which hypothetically might have caused death if it were more severe. 
• Requires hospitalization or prolongation of existing hospitalization.  
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NOTE: In general, hospitalization signifies that the subject was admitted (usually 
involving at least an overnight stay) to the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or outpatient setting.  
• Results in disability/incapacity. 
NOTE: The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. This definition is not intended to include experiences 
of relatively minor medical significance, such as uncomplicated headache, nausea, 
vomiting, diarrhea, influenza, and accidental trauma (eg, sprained ankle), which may 
interfere or prevent everyday life functions, but do not constitute a substantial 
disruption.  
• Is a congenital anomaly/birth defect.  
• Is considered a significant medical AE by the investigator based on medical judgment 
(eg, may jeopardize the subject or may require medical/surgical intervention to 
prevent one of the outcomes listed above).  
The following are NOT considered SAEs: 
• Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline 
• Hospitalization for social/convenience considerations 
• Scheduled therapy for the target disease of the study, including admissions for 
transfusion support or convenience 
9.5. 
Suspected Unexpected Serious Adverse Reaction 
A suspected unexpected serious adverse reaction (SUSAR) is a serious adverse reaction that is 
both unexpected (ie, not present in the product’s Reference Safety Information [RSI]) and meets 
the definition of a serious adverse drug reaction (SADR), the specificity or severity of which is 
not consistent with those noted in the BGB-DXP593 Investigator’s Brochure. 
9.6. 
Timing, Frequency, and Method of Capturing Adverse Events and 
Serious Adverse Events 
9.6.1. 
Adverse Event Reporting Period 
After informed consent has been signed but prior to the administration of the study drug, only 
SAEs should be reported. 
After initiation of the study drug, all AEs and SAEs, regardless of relationship to study drug, will 
be reported until 30 days after the dose of study drug or EOS Visit, whichever is later. After the 
period, the investigator should report any SAEs that are considered to be related to the study 
drug. 
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9.6.2. 
Reporting of Serious Adverse Events 
9.6.2.1. 
Prompt Reporting of Serious Adverse Events 
As soon as the investigator determines that an AE meets the protocol definition of a SAE, the 
event must be reported promptly (within 24 hours) to the sponsor or designee as described in 
Table 4. 
Table 4: 
Timeframe and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee 
 
Timeframe for 
Making Initial 
Report 
Documentation 
Method 
Timeframe for 
Sending Follow-
up Report 
Documentation 
Method 
Reporting 
Method 
All SAEs 
Within 24 hours 
of first knowledge 
of the SAE 
SAE Report 
As expeditiously 
as possible 
SAE Report 
Email or fax 
SAE report 
form  
Abbreviations: SAE, serious adverse event. 
9.6.2.2. 
Completion and Transmission of the Serious Adverse Event Report 
Once an investigator becomes aware that a SAE has occurred in a subject, he/she is to report the 
information to the sponsor within 24 hours as outlined in Section 9.6.2.1.  The SAE report will 
always be completed as thoroughly as possible with all available details of the event, and 
forwarded to the sponsor or designee within the designated time frames.   
If the investigator does not have all information regarding a SAE, he/she is not to wait to receive 
additional information before notifying the sponsor or designee of the SAE and completing the 
form. The form will be updated when additional information is received.  
The investigator must always provide an assessment of causality for each SAE as described in 
Section 9.3.3. 
The sponsor will provide contact information for SAE receipt. 
9.6.2.3. 
Regulatory Reporting Requirements for Serious Adverse Events 
The investigator will promptly report all SAEs to the sponsor in accordance with the procedures 
detailed in Section 9.6.2.1. The sponsor has a legal responsibility to notify, as appropriate, both 
the local regulatory authority and other regulatory agencies about the safety of a product under 
clinical investigation.  
The investigator, or responsible person according to local requirements, will comply with the 
applicable local regulatory requirements related to the reporting of SAEs to regulatory authorities 
and the IRB/IEC. 
All SUSARs (as defined in Section 9.5), will be submitted to all applicable regulatory authorities 
and investigators for BGB-DXP593 studies. 
When a study center receives an initial or follow-up safety report or other safety information  
(eg, revised Investigator’s Brochure) from the sponsor, the investigator or designated responsible 
person is required to promptly notify his/her IRB or IEC.  The investigator should place copies 
of Safety Reports from the sponsor in the Investigator Site File. 
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9.6.3. 
Eliciting Adverse Events 
The investigator or designee will ask about AEs by asking the following standard questions: 
• How are you feeling? 
• Have you had any medical problems since your last visit? 
• Have you taken any new medicines since your last visit? 
9.6.4. 
Death 
Death is an outcome and not usually considered an event. If the only information available is 
death and the cause of death is unknown, then the death is reported as an event, eg, “death," 
“death of unknown cause," or “death unexplained." 
9.6.5. 
Pregnancies 
If the partner of a male subject becomes pregnant within 30 days after the single dose of study 
drug, a pregnancy report form is required to be completed and expeditiously submitted to the 
sponsor to facilitate outcome follow-up. Information on the status of the mother and child will be 
forwarded to the sponsor. Generally, follow-up will be no longer than 6 to 8 weeks following the 
estimated delivery date. Any premature termination of the pregnancy will be reported. 
While pregnancy itself is not considered to be an AE, any pregnancy complication or elective 
termination of a pregnancy for medical reasons will be recorded as an AE or SAE. 
An abortion, whether accidental, therapeutic, or spontaneous should be always reported as a 
SAE. Similarly, any congenital anomaly/birth defect in a child born to a subject exposed to the 
study drug should be recorded and reported as a SAE. 
9.6.6. 
Expedited Reporting to Health Authorities, Investigators, Institutional Review 
Boards, and Ethics Committees 
The sponsor will promptly assess all SAEs against cumulative study drug experience to identify 
and expeditiously communicate new safety findings to regulatory authorities, investigators, 
IRBs, and IECs based on applicable legislation. 
To determine the reporting requirements for individual SAEs, the sponsor will assess the 
expectedness of the SAEs using the following reference documents: 
• BGB-DXP593 Investigator’s Brochure 
9.6.7. 
Reporting Infusion-Related Reactions 
The symptoms of infusion-related reactions may include but are not limited to fever, chills/rigor, 
nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, 
myalgia, dizziness, or hypertension. Severe reactions may include acute respiratory distress 
syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock. Individual signs 
and symptoms of an infusion reaction should be recorded each as a separate AE in the eCRF and 
identified as an infusion-related reaction. Refer to the eCRF completion guidelines for details. 
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9.7. 
Management of Infusion-Related Reactions and Severe 
Hypersensitivity Reactions  
As a routine precaution, following completion of the study drug administration, subjects must be 
monitored for at least 2 hours after the infusion of study drug in a setting where emergency 
medical equipment and staff who are trained to respond to medical emergencies are available. 
The management of infusion-related reactions, and severe hypersensitivity reactions according to 
the NCI-CTCAE criteria are outlined in the following subsections. 
9.7.1. 
Managing Infusion-Related Reactions 
The symptoms of infusion-related reactions include fever, chills/rigor, nausea, pruritus, 
angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness 
or hypertension. Severe reactions may include acute respiratory distress syndrome, myocardial 
infarction, ventricular fibrillation, and cardiogenic shock. 
Subjects should be closely monitored for infusion-related reactions. Immediate access to an 
Intensive Care Unit or equivalent environment and appropriate medical therapy (including 
epinephrine, corticosteroids, intravenous antihistamines, bronchodilators, and oxygen) must be 
available to treat infusion-related reactions. 
Treatment modifications for symptoms of infusion-related reactions due to the study drug are 
provided in Table 5. 
Table 5: 
Treatment Modifications for Symptoms of Infusion-Related Reactions Due to 
Study Drug 
NCI-CTCAE grade 
Treatment modification for Study Drug 
Grade 1 - mild 
Mild transient reaction; infusion interruption not 
indicated; intervention not indicated. 
Decrease infusion rate by 50%. Any worsening is 
closely monitored. Medical management as needed.  
Grade 2 - moderate 
Therapy or infusion interruption indicated but responds 
promptly to symptomatic treatment (eg, antihistamines, 
nonsteroidal anti-inflammatory drugs, narcotics, 
intravenous fluids); prophylactic medications indicated 
for ≤ 24 hours. 
Stop infusion. Infusion may be resumed at 50% of 
previous rate once infusion-related reaction has 
resolved or decreased to Grade 1 in severity within 2 
hours of the infusion interruption. The subject should 
be discontinued from study drug if the Grade 2 
infusion-related reaction has not resolved or decreased 
over 2 hours of the infusion interruption.  
Any worsening is closely monitored. Proper medical 
management should be instituted as described below.   
Grade 3 – severe 
Prolonged (eg, not rapidly responsive to symptomatic 
medication and/or brief interruption of infusion); 
recurrence of symptoms following initial improvement; 
hospitalization indicated for clinical sequelae. 
Immediately stop the infusion. Proper medical 
management should be instituted as described below. 
The subject should be withdrawn from study drug 
treatment. 
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NCI-CTCAE grade 
Treatment modification for Study Drug 
Grade 4 – life-threatening 
Life-threatening consequences; urgent intervention 
indicated. 
Immediately stop the infusion. Proper medical 
management should be instituted as described below. 
The subject should be withdrawn from study drug 
treatment. 
Hospitalization is recommended. 
Abbreviations: NCI-CTCAE, National Cancer Institute-Common Terminology Criteria for Adverse Events. 
NCI-CTCAE Grade 1 or 2 infusion reaction: Proper medical management should be 
instituted, as indicated per the type of reaction. This includes but is not limited to an 
antihistamine (eg, diphenhydramine or equivalent), antipyretic (eg, paracetamol or equivalent), 
and, if considered indicated, oral or intravenous glucocorticoids, epinephrine, bronchodilators, 
and oxygen.  
NCI-CTCAE Grade 3 or 4 infusion reaction: Proper medical management should be instituted 
immediately, as indicated per type and severity of the reaction. This includes but is not limited to 
oral or intravenous antihistamines, antipyretics, glucocorticoids, epinephrine, bronchodilators, 
and oxygen. 
9.7.2. 
Severe Hypersensitivity Reactions  
If hypersensitivity reaction occurs, the subject must be treated according to the best available 
medical practice as described in the complete guideline for emergency treatment of anaphylactic 
reactions according to the Working Group of the Resuscitation Council (United Kingdom) (Soar 
et al 2008). Subjects should be instructed to report any delayed reactions to the investigator 
immediately. 
In the event of a systemic anaphylactic/anaphylactoid reaction, the infusion must be stopped 
immediately and the subject discontinued from the study. Systemic anaphylactic/anaphylactoid 
reactions typically manifest within minutes following administration of the drug/antigen and are 
characterized by respiratory distress; laryngeal edema; and/or intense bronchospasm; and are 
often followed by vascular collapse or shock without antecedent respiratory difficulty; cutaneous 
manifestations such as pruritus and urticaria with/without edema; and gastrointestinal 
manifestations such as nausea, vomiting, crampy abdominal pain, and diarrhea. 
The subject will be administered epinephrine injection and dexamethasone infusion if 
hypersensitivity reaction is observed. The subject should then be placed on monitor immediately 
and an Intensive Care Unit should be alerted for possible transfer if needed. 
 
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10. 
STATISTICAL METHODS AND SAMPLE SIZE 
DETERMINATION 
Details of the statistical analyses will be included in a separate Statistical Analysis Plan.  
10.1. 
Statistical Analysis 
10.1.1. 
Randomization Method 
As discussed in Section 7.4, subjects will be randomized using the IRT system for this study. 
10.1.2. 
Analysis Sets  
The Safety Analysis Set will include all the subjects who received the study drug. 
The PK Analysis Set will include all the subjects who received the study drug and had any 
measurable concentration of study drug. 
The ADA Analysis Set include all the subjects who received the study drug and in whom both 
baseline ADA and at least 1 postbaseline ADA results are available. 
10.1.3. 
Subject Disposition 
The number of subjects randomized, treated, and discontinued from study drug and/or study will 
be counted.  The primary reason for study drug and/or study discontinuation will be summarized 
according to the categories in the eCRF. 
Major protocol deviations will be summarized and listed by each category. 
10.1.4. 
Demographics and Other Baseline Characteristics 
Demographic and other baseline characteristics will be summarized in the Safety Analysis Set 
using descriptive statistics. Summary statistics will be presented for continuous demographic and 
baseline characteristic variables by dose level. The number (percentage) of subjects in each 
category will be presented for categorical variables by dose level.  Continuous variables include, 
but are not limited to age, weight, height, and BMI. Categorical variables include, but are not 
limited to, sex, race, and ethnicity. 
10.1.5. 
Prior and Concomitant Therapy 
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
drug codes. Concomitant medications will be further coded to the appropriate Anatomical 
Therapeutic Chemical code indicating therapeutic classification.  Prior and concomitant 
medications will be summarized by dose level.  
Prior medications will be defined as medications that started before the dose of study drug.  
Concomitant medications will be defined as medications that (1) started before the dose of study 
drug and were continuing at the time of the dose of study drug, or (2) started on or after the date 
of the dose of study drug up to 30 days after the dose of study drug. 
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10.2. 
Efficacy Analyses 
There is no efficacy analysis planned for this study. 
10.3. 
Safety Analyses 
Adverse events, ECGs, vital signs, and laboratory data will be reviewed and summarized on an 
ongoing basis during the study to evaluate the safety of subjects.  Descriptive statistics will be 
used to analyze all safety data. 
10.3.1. 
Extent of Exposure 
The extent of study drug exposure will be summarized descriptively for the single dose 
administered by dose level. The number (percentage) of subjects with dose interruption and 
infusion rate decreased will be summarized with the respective reasons by dose level. 
Subject data listings will be provided for all dosing records and for calculated summary statistics. 
10.3.2. 
Adverse Events 
The AE verbatim descriptions (as recorded by the investigator on the eCRF) will be classified 
into standardized medical terminology using the Medical Dictionary for Regulatory Activities 
(MedDRA).  Adverse events will be coded to MedDRA by the lowest level term, preferred term 
(PT), and primary system organ class (SOC).  
A TEAE is defined as an AE that had an onset date or a worsening in severity from baseline on 
or after the administration of study drug and up to 30 days after the dose of study drug. Only 
those AEs that were treatment-emergent will be included in summary tables.   
The incidence of TEAEs will be reported as the number (percentage) of subjects with TEAEs by 
SOC and PT. A subject will be counted only once by the highest severity grade according to 
NCI-CTCAE version 5.0 within a SOC and PT, even if the subject experienced more than one 
TEAE within a specific SOC and PT.   
The number (percentage) of subjects with TEAEs will also be summarized by relationship to the 
study drug.  Treatment-related AEs include those events considered by the investigator to be 
related to study drug or with missing assessment of the causal relationship. Treatment-emergent 
SAEs and treatment-related TEAEs will also be summarized.  All AEs, treatment-emergent or 
otherwise, will be presented in subject data listings. 
10.3.3. 
Laboratory Analyses 
Clinical laboratory (clinical chemistry, hematology, coagulation, and urinalysis) values will be 
evaluated for each laboratory parameter as appropriate.  Abnormal laboratory values will be 
flagged and identified as those outside (above or below) the normal range.  Laboratory 
parameters and their changes from baseline will be summarized by visit and dose level.  Change 
from baseline will only be summarized for subjects with both baseline and postbaseline 
measurements. 
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10.3.4. 
Vital Signs 
Descriptive statistics for vital sign parameters (systolic and diastolic blood pressure, pulse rate, 
respiratory rate, and body temperature) and changes from baseline will be summarized by visit 
and dose level. 
10.3.5. 
Electrocardiogram 
Descriptive statistics for ECG parameters and changes from baseline will be summarized by visit 
and dose level.  
10.4. 
Pharmacokinetic Analyses 
Noncompartmental analysis will be carried out for BGB-DXP593 serum concentrations.  The PK 
analyses will include only subjects with enough data to enable estimation of key parameters.  
Parameters, such as Cmax, tmax, t1/2, AUCt, AUCinf, AUC0-29, CL, and Vz (as appropriate for data 
collected), may be derived and summarized with descriptive statistics (sample size, mean, 
standard deviation, coefficient of variance, median, minimum, maximum, geometric mean, 
geometric coefficient of variance).  Other PK parameters may be calculated if supported by the 
data. Individual serum concentration-versus-time data will be tabulated and plotted by dose level.  
Additional PK analyses (such as modeling and simulation using nonlinear mixed effects 
modelling) may be conducted as appropriate. 
10.5. 
Immunogenicity Analyses 
The immunogenicity results will be summarized using descriptive statistics by the number and 
percentage of subjects who develop detectable ADAs.  The incidence of positive and neutralizing 
ADAs will be reported for evaluable subjects. The effect of immunogenicity on PK, and safety 
may be evaluated if data allow. 
10.6. 
 Sample Size Consideration 
A sample size of 8 subjects at each dose level (6 active and 2 control) totaling up to 30 subjects 
(including possible replacement) is not based on any statistical considerations.  The sample size 
is based on the clinical consideration to provide safety and tolerability information and 
pharmacological considerations with the need to minimize exposure to healthy subjects at each 
dose level.  No formal inferential statistics will be applied to the safety or PK data. 
10.7. 
Interim Analysis 
There is no formal interim analysis planned for this study. 
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11. 
STUDY COMMITTEE 
11.1. 
Safety Monitoring Committee 
An SMC will be established and will include both the sponsor (including the medical monitor 
and study team members from Pharmacovigilance/Drug Safety, Clinical Pharmacology, and 
Biostatistics with other members as appropriate) and investigators.  
The SMC will review safety, laboratory data and make recommendations on dose escalations for 
this study. The SMC may also be called upon by the sponsor on an ad hoc basis where applicable 
to the conduct of the study. 
A separate charter will outline the details for the composition and responsibility of the SMC. 
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12. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS 
The investigator must maintain adequate and accurate records to ensure that the conduct of the 
study may be fully documented. Such records include but are not limited to the protocol, 
protocol amendments, ICFs, and documentation of IRB/IEC and governmental approvals. In 
addition, at the end of the study, the investigator will receive subject data, which will include an 
audit trail containing a complete record of all changes to such data. 
12.1. 
Access to Information for Monitoring 
In accordance with International Council for Harmonisation GCP guidelines, the study monitor 
must have direct access to the investigator’s source documentation to verify the data recorded in 
the eCRFs for consistency. 
The monitor is responsible for routine review of the eCRFs at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries in the eCRFs. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected during these monitoring visits are resolved. 
12.2. 
Access to Information for Auditing or Inspections 
Representatives of regulatory authorities or of BeiGene may conduct inspections or audits any 
time during or after completion of this clinical study. If the investigator is notified of an 
inspection by a regulatory authority, the investigator agrees to notify the sponsor or its designee 
immediately. The investigator agrees to provide to representatives of a regulatory agency or 
BeiGene access to records, facilities, and personnel for the effective conduct of any inspection or 
audit. 
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13. 
QUALITY ASSURANCE AND QUALITY CONTROL 
13.1. 
Regulatory Authority Approval 
The sponsor will obtain approval to conduct the study from the appropriate regulatory agency in 
accordance with any applicable country-specific regulatory requirements or file the protocol to 
the appropriate regulatory agency before the study is initiated at a study center in that country. 
13.2. 
Quality Assurance 
To ensure compliance with GCP and all applicable regulatory requirements, the sponsor may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory inspection 
of this study. Such audits/inspections can occur at any time during or after completion of the 
study. If an audit or inspection occurs, the investigator and institution agree to allow the 
auditor/inspector direct access to all relevant documents and to allocate his/her time and the time 
of his/her personnel to the auditor/inspector to discuss findings and any relevant issues. 
13.3. 
Study Site Inspections 
This study will be organized, performed, and reported in compliance with the protocol, standard 
operating procedures, working practice documents, and applicable regulations and guidelines. 
Site audits may be performed periodically by the sponsor’s or the contract research 
organization’s qualified compliance auditing team, which is an independent function from the 
study team responsible for conduct of the study. 
Site visits will be conducted by the sponsor or an authorized representative to inspect study data, 
subjects’ medical records, and eCRFs. The investigator is to permit national and local health 
authorities; sponsor study monitors, representatives, and collaborators; and IRB/IEC members to 
inspect all facilities and records relevant to this study. 
13.4. 
Drug Accountability 
The investigator or designee (ie, unblinded pharmacist[s]) are responsible for ensuring adequate 
accountability of all used and unused study drug. This includes acknowledgment of receipt of 
each shipment of study drug (quantity and condition), subject drug dispensation records, and 
returned or destroyed study drug. Dispensation records will document quantities received from 
BeiGene’s designated depot or its designee and quantities dispensed to subjects, including 
batch/lot number, date dispensed, subject identifier number, and the initials of the person 
dispensing the medication. 
At study initiation, the monitor will evaluate the site’s standard operating procedure for study 
drug disposal/destruction to ensure that it complies with BeiGene requirements specified in the 
Pharmacy Manual. At appropriate times during the conduct of the study or at the end of the study 
following final drug inventory reconciliation by the monitor, the study site will dispose of and/or 
destroy all unused study drug supplies, including empty containers, according to these 
procedures. If the site cannot meet BeiGene’s requirements specified in the Pharmacy Manual 
for disposal, arrangements will be made between the site and BeiGene or its representative for 
destruction or return of unused study drug supplies. 
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All drug supplies and associated documentation will be periodically reviewed and verified by the 
study monitor over the course of the study. 
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14. 
ETHICS/PROTECTION OF HUMAN SUBJECTS 
14.1. 
Ethical Standard 
This study will be conducted by the principal investigator and the study center in full 
conformance with the International Council for Harmonisation E6 guideline for GCP and the 
principles of the Declaration of Helsinki or the laws and regulations of the country in which the 
research is conducted, whichever affords the greater protection to the subject. The study will also 
comply with the requirements of the International Council for Harmonisation E2A guideline 
(Clinical Safety Data Management: Definitions and Standards for Expedited Reporting). 
14.2. 
Institutional Review Board/Independent Ethics Committee 
This protocol, the ICFs, any information to be given to the subject, and relevant supporting 
information must be submitted, reviewed, and approved by the IRB/IEC before the study is 
initiated. In addition, any subject recruitment materials must be approved by the IRB/IEC. 
Copies of the IEC/IRB correspondence and approval of the amended ICF/other information and 
the approved amended ICF/other information must be forwarded to the sponsor promptly. 
The principal investigator is responsible for providing written summaries of the status of the 
study to the IRB/IEC annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/IEC. Investigators are also responsible for promptly 
informing the IRB/IEC of any protocol amendments. In addition to the requirements for 
reporting all AEs to the sponsor, investigators must comply with requirements for reporting 
SAEs to the local health authority and IRB/IEC. Investigators may receive written 
Investigational New Drug Safety Reports or other safety-related communications from the 
sponsor. Investigators are responsible for ensuring that such reports are reviewed and processed 
in accordance with health authority requirements and the policies and procedures established by 
their IRB/IEC and archived in the site’s study file. 
14.2.1. 
Protocol Amendments 
Any protocol amendments will be prepared by the sponsor. All protocol modifications must be 
submitted to competent authorities according to local requirements and to the IRB/IEC together 
with, if applicable, a revised model ICF in accordance with local requirements. Written 
documentation from competent authorities (according to local requirements) and from the 
IRB/IEC and required site approval must be obtained by the sponsor before changes can be 
implemented, except for changes necessary to eliminate an immediate hazard to subjects or 
changes that involve logistical or administrative aspects only (eg, change in medical monitor or 
contact information). 
Information on any change in risk and/or change in scope must be provided to subjects already 
actively participating in the study, and they must read, understand, and sign each revised ICF 
confirming their willingness to remain in the study. 
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14.3. 
Informed Consent 
The sponsor’s sample ICF will be provided to each site. If applicable, it will be provided in a 
certified translation of the local language. The final IRB/IEC-approved ICFs must be provided to 
the sponsor for health authority submission purposes according to local requirements. 
The ICFs must be signed and dated by the subject or the subject’s legally authorized 
representative before his or her participation in the study. The case history or clinical records for 
each subject shall document the informed consent process and that written informed consent was 
obtained before participation in the study. 
The ICFs will be revised whenever there are changes to study procedures or when new 
information becomes available that may affect the willingness of the subject to participate. The 
final revised IRB/IEC-approved consent forms must be provided to the sponsor for health 
authority submission purposes. 
Subjects must be re-consented to the most current version of the ICFs (or to a significant new 
information/findings addendum in accordance with applicable laws and IRB/IEC policy) during 
their participation in the study. For any updated or revised ICFs, the case history or clinical 
records for each subject shall document the informed consent process and that written informed 
consent was obtained using the updated/revised ICFs for continued participation in the study. 
A copy of each signed ICF must be provided to the subject or the subject’s legally authorized 
representative. All signed and dated ICFs must remain in each subject’s study file or in the site 
file and must be available for verification by study monitors at any time. 
14.4. 
Subject and Data Confidentiality 
The principal investigator and sponsor will maintain confidentiality and privacy standards by 
following applicable data privacy laws covering the collection, storage, transmission, and 
processing of subjects’ personal and medical information. 
The principal investigator shall code the medical information obtained during the study with a 
unique subject identification number assigned to each subject enrolled in the study. This 
approach ensures that subjects’ names are not included in any data set transmitted to any sponsor 
location. 
Subject medical information obtained during this study is confidential and may only be disclosed 
to third parties as permitted by the signed ICF (or a separate authorization for the use and 
disclosure of personal health information that has been signed by the subject), unless permitted 
or required by law. 
In the event of a breach of the confidentiality of a subject’s personal and medical information, 
the principal investigator and sponsor, as appropriate, shall fulfill all mediation steps and 
reporting obligations under applicable data privacy laws. 
Medical information may be given to a subject’s personal physician or other appropriate medical 
personnel responsible for the subject’s welfare for treatment purposes. 
Data generated during this study must be available for inspection upon request by representatives 
of the Therapeutic Goods Administration in Australia and all other national and local health 
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authorities; by sponsor monitors, representatives, and collaborators; and by the IRBs/IECs for 
each study site, as appropriate. 
The investigator must ensure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. The investigator agrees that all information 
received from the sponsor, including but not limited to the this protocol, eCRFs, the 
Investigational New Drug, and any other study information, remain the sole and exclusive 
property of the sponsor during the conduct of the study and thereafter. This information is not to 
be disclosed to any third party (except employees or agents directly involved in the conduct of 
the study or as required by law) without prior written consent from the sponsor. The investigator 
further agrees to take all reasonable precautions to prevent the disclosure by any employee or 
agent of the study site to any third party or otherwise into the public domain. 
If a written contract for the conduct of the study includes confidentiality provisions inconsistent 
with this section is executed, that contract’s provisions shall apply to the extent they are 
inconsistent with this section. 
14.5. 
Financial Disclosure 
Investigators are required to provide the sponsor with sufficient accurate financial information in 
accordance with regulations to allow the sponsor to submit complete disclosure or certification to 
the absence of certain financial interest of the clinical investigators and/or disclose those 
financial interests, as required, to the appropriate health authorities. This is intended to ensure 
financial interests and arrangements of the clinical investigators with BeiGene that could affect 
reliability of data submitted to health authorities are identified and disclosed by the sponsor. 
Investigators are responsible for providing information about their financial interests before 
participation in the study and to update this information if any relevant changes occur during the 
study and for 1 year after completion of the study (ie, last subject, last visit). 
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15. 
DATA HANDLING AND RECORD KEEPING 
15.1. 
Data Collection and Management Responsibilities 
15.1.1. 
Data Entry in the Electronic Case Report Form 
All study-related data collected or received by the investigator or study team shall be promptly 
entered into the eCRFs. In no event should the entry of the study data into the eCRF be later than 
what is stipulated in the site contract after the data is collected or received by the investigator or 
study team without prior communication with and approval by the sponsor. 
15.1.2. 
Data Collection 
Data required by the protocol will be entered into an electronic data capture (EDC) system. 
Data collection in the eCRF should follow the instructions described in the eCRF Completion 
Guidelines. The investigator has ultimate responsibility for the collection and reporting of all 
clinical data entered in the eCRF. The e-signature of the investigator or designee must be 
provided in the EDC system to attest to its accuracy, authenticity, and completeness. 
Data contained in the eCRFs are the sole property of BeiGene and should not be made available 
in any form to third parties without written permission from BeiGene, except for authorized 
representatives of BeiGene or appropriate regulatory authorities. 
15.1.3. 
Data Management/Coding 
All final subject data, both eCRF and external data (eg, laboratory data), collected according to 
the protocol will be stored by BeiGene at the end of the study. 
Standard procedures (including following data review guidelines, computerized validation to 
produce queries, and maintenance of an audit file that includes all database modifications) will 
be followed to support accurate data collection. Data will be reviewed for outliers, logic, data 
inconsistencies, and completeness. 
During the study, a study monitor or a clinical research associate will make site visits to review 
protocol compliance, compare eCRFs against individual subject’s medical records, and ensure 
that the study is being conducted according to pertinent regulatory requirements. 
The eCRF entries will be verified with source documentation. The review of medical records 
will be performed in a manner to ensure that subject confidentiality is maintained. Checking the 
eCRFs for completeness, clarity, and cross-checking with source documents is required to 
monitor the progress of the study. Direct access to source data is also required for inspections 
and audits, and will be carried out with due consideration to data protection and medical 
confidentiality. 
The AE verbatim descriptions (the investigator’s description from the eCRF) will be coded using 
MedDRA. AEs will be coded to MedDRA by the lowest level term, PT, and primary SOC. 
Concomitant medications will be coded using the World Health Organization Drug Dictionary. 
Concomitant diseases/medical history will be coded using MedDRA. 
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15.2. 
Study Records Retention 
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into at least 1 of the following 2 categories: 1) investigator’s study file and/or 
2) subject clinical source documents. 
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, 
IRB/IEC and governmental approval with correspondence, ICFs, drug records, staff curriculum 
vitae and authorization forms, and other appropriate documents and correspondence. 
Subject clinical source documents (usually defined by the project in advance to record key 
efficacy/safety parameters independent of the eCRFs) would include but not be limited to 
documents such as the following: subject hospital/clinic records, physician’s and nurse’s notes, 
appointment book, original laboratory reports, ECG, electroencephalogram, x-ray, pathology and 
special assessment reports, consultant letters, screening and enrollment logs, etc. 
Following closure of the study, the investigator must maintain all study records in a safe and 
secure location. The records must be maintained to allow easy and timely retrieval, when needed 
(eg, audit or inspection), and, whenever feasible, to allow any subsequent review of data in 
conjunction with assessment of the facility, supporting systems, and personnel. Where permitted 
by local laws/regulations or institutional policy, some or all of these records can be maintained in 
a format other than hard copy (eg, microfiche, scanned, electronic); however, caution needs to be 
exercised before such action is taken. The investigator must ensure that all reproductions are 
legible, are a true and accurate copy of the original, and meet accessibility and retrieval 
standards, including regenerating a hard copy, if required. Furthermore, the investigator must 
ensure there is an acceptable backup of these reproductions and that an acceptable quality control 
process exists for making these reproductions. 
The sponsor will inform the investigator of the time period for retaining these records to comply 
with all applicable regulatory requirements. The minimum retention time will meet the strictest 
standard applicable to that study center for the study, as dictated by any institutional 
requirements, local laws or regulations, or the sponsor’s standards/procedures; otherwise, the 
retention period will default to 15 years. 
The investigator must notify the sponsor of any changes in the archival arrangements including 
but not limited to the following: archival at an off-site facility or transfer of ownership of or 
responsibility for the records in the event the investigator leaves the study center. 
If the investigator cannot guarantee this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and BeiGene to 
store these in sealed containers outside of the site so that they can be returned sealed to the 
investigator in case of a regulatory audit. When source documents are required for the continued 
care of the subject, appropriate copies should be made for storage outside of the site. 
Biological samples at the conclusion of this study may be retained as outlined in the agreement 
with the CRO managing the biological samples, for the shorter of: a period of up to 10 years or 
as allowed by your IRB/IEC. 
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15.3. 
Protocol Deviations 
The investigator is responsible for ensuring that the study is conducted in accordance with the 
procedures and evaluations described in this protocol. Investigators assert they will apply due 
diligence to avoid protocol deviations and shall report all protocol deviations to the sponsor. 
The investigator is to document and explain any deviations from the approved protocol. The 
investigator must promptly report any major deviations that might impact subject safety and/or 
data integrity to the sponsor and to the IRB/IEC, in accordance with established IRB/IEC 
policies and procedures. 
15.4. 
Study Report and Publications 
A clinical study report will be prepared and provided to the regulatory agency(ies). BeiGene will 
ensure that the report meets the standards set out in the International Council for Harmonisation 
Guideline for Structure and Content of Clinical Study Reports (ICH E3). An abbreviated report 
may be prepared in certain cases. 
The results of this study will be published or presented at scientific meetings in a timely, 
objective, and clinically meaningful manner that is consistent with good science, industry and 
regulatory guidance, and the need to protect the intellectual property of the sponsor, regardless of 
the outcome of the study. The data generated in this clinical study are the exclusive property of 
the sponsor and are confidential. For a multicenter study, the first publication or disclosure of 
study results shall be a complete, joint multicenter publication, or disclosure coordinated by the 
sponsor. Thereafter, any secondary publications will reference the original publication(s). 
Authorship will be determined by mutual agreement and all authors must meet the criteria for 
authorship established by the International Committee of Medical Journal Editors Uniform 
Requirements for Manuscripts or stricter local criteria (International Committee of Medical 
Journal Editors 2016). 
Each investigator agrees to submit all manuscripts, abstracts, posters, publications, and 
presentations (both oral and written) to the sponsor for review before submission or presentation 
in accordance with the clinical study agreement. This allows the sponsor to protect proprietary 
information, provide comments based on information from other studies that may not yet be 
available to the investigator, and ensure scientific and clinical accuracy. The details of the 
processes of producing and reviewing reports, manuscripts, and presentations based on the data 
from this study will be presented in the investigator’s clinical study agreement. Each investigator 
agrees that, in accordance with the terms of the clinical study agreement, a further delay of the 
publication/presentation may be requested by the sponsor to allow for patent filings and/or 
protection in advance of the publication/presentation. 
15.5. 
Study and Study Center Closure 
Upon completion of the study, the monitor will conduct the following activities in conjunction 
with the investigator or study center personnel, as appropriate: 
• Return/provide all study data to the sponsor 
• Resolution and closure of all data queries 
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• Accountability, reconciliation, and arrangements for unused study drug 
• Review of study records for completeness 
• Collection of all study documents for the trial master file filing according to GCP and 
local regulation 
• Shipment of samples (including but not limited to those for PK, ADA, and 
biomarkers) to the assay laboratory for central laboratory analysis according to 
protocol and laboratory manual requirements 
In addition, the sponsor reserves the right to suspend the enrollment or prematurely discontinue 
this study either at a single study center or at all study centers at any time for any reason. 
Potential reasons for suspension or discontinuation include but are not limited to: safety or 
ethical issues or noncompliance with this protocol, GCP, the sponsor’s written instructions, the 
clinical study agreement, or applicable laws and regulations. If the sponsor determines such 
action is needed, the sponsor will discuss this with the investigator (including the reasons for 
taking such action) at that time. When feasible, the sponsor will provide advance notification to 
the investigator of the impending action before it takes effect. 
The sponsor will promptly inform all other investigators and/or institutions conducting the study 
if the study is suspended or terminated for safety reasons. The sponsor will also inform the 
regulatory authorities of the suspension or termination of the study and the reason(s) for the 
action. If required by applicable regulations, the investigator must inform the IEC/IRB promptly 
and provide the reason for the suspension or termination. 
If the study is prematurely discontinued, all study data must still be provided to the sponsor. In 
addition, arrangements will be made for the return of all unused study drug in accordance with 
the applicable sponsor procedures for the study. 
Financial compensation to the investigators and/or institutions will be in accordance with the 
clinical study agreement established between the investigator and/or institutions and the sponsor. 
15.6. 
Information Disclosure and Inventions 
All rights, title, and interests in any inventions, know-how, or other intellectual or industrial 
property rights that are conceived or reduced to practice by the study center personnel during the 
course of or as a result of the study are the sole property of the sponsor and are hereby assigned 
to the sponsor. 
If a written contract for the conduct of the study, which includes ownership provisions 
inconsistent with this statement, is executed between the sponsor and the study center, that 
contract’s ownership provisions shall apply rather than this statement. 
All information provided by the sponsor and all data and information generated by the study 
center as part of the study (other than a subject’s medical records) are the sole property of the 
sponsor and will be kept confidential by the investigator and other study center personnel.  
This information and data will not be used by the investigator or other study center personnel for 
any purpose other than conducting the study without the prior written consent of the sponsor. 
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These restrictions do not apply to: 
• Information that becomes publicly available through no fault of the investigator or 
study center personnel 
• Information that is necessary to disclose in confidence to an IEC/IRB solely for the 
evaluation of the study 
• Information that is necessary to disclose to provide appropriate medical care to a 
subject 
• Study results that may be published as described in Section 15.4  
If a written contract for the conduct of the study, which includes provisions inconsistent with this 
statement is executed, that contract’s provisions shall apply rather than this statement. 
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16. 
REFERENCES 
BeiGene Investigator’s Brochure, BGB-DXP593. Edition 1.0, August 2020. 
Cao YL, Su B, Guo XH, et al. Potent Neutralizing Antibodies against SARS-CoV-2 Identified by 
High-Throughout Single-Cell Sequencing of Convalescent Patients’ B Cells. Cell 2020; 182: 
1-12. 
FDA, CDER: Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for 
Therapeutics in Adult Healthy Volunteers. 2005. 
Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: The Reality and Challenges. 
Journal of Microbiology, Immunology and Infection 2020; 53: 436-43. 
International Committee of Medical Journal Editors. Recommendations for the Conduct, 
Reporting, Editing, and Publication of Scholarly Work in Medical Journals. 2016. Available 
online: http://www.icmje.org. Accessed 31 July 2020. 
Mahmood I, Balian JD. The Pharmacokinetic Principals Behind Scaling From Preclinical Results 
to Phase I Protocols. Clin Pharmacokinet 1999; 36(1): 1-11. 
Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions--guidelines 
for healthcare providers. Resuscitation. 2008; 77(2):157-69.  
Sullivan HC, Roback JD. Convalescent Plasma: Therapeutic Hope or Hopeless Strategy in the 
SARS-CoV-2 Pandemic. Transfusion Medicine Reviews. 2020; 
https://doi.org/10.1016/j.tmrv.2020.04.001 
Zhou GY, Zhao Q. Perspectives on Therapeutic Neutralizing Antibodies against the Novel 
Coronavirus SARS-CoV-2. Int. J. Biol. Sci. 2020; 16(10): 1718-23. 
Zhou P, Yang XL, Wang XG, et al. A Pneumonia Outbreak Associated With a New Coronavirus 
of Probable Bat Origin. Nature 2020; 579: 1–4. 
 
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APPENDIX 1. SCHEDULE OF ASSESSMENTS  
Period 
Screening 
Admission 
to Unit 
Treat
ment 
Follow-up 
Day 
-28 to -1 
-1 
D1 a 
D2 
D3 
D4 
D5 
D8 
D
15 
D
22 
D
29 
D
43 
D
57 
D
71 
D
85  
D113 
/ 
EOS 
b 
Safety 
Follow-up 
Visit c 
Visit Window (day) 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
± 
1 
± 
1 
± 
1 
± 
2 
± 
2 
± 
2 
± 
2 
± 2 
± 3 
Informed consent d 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography/prior 
medications 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization f 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BGB-DXP593 single 
dose administration g 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Discharge 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
Safety Assessments 
Vital signs/ 
height and weight h 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Complete physical 
examination i 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Targeted 
physical examination i 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECG j 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Cardiac Telemetry k 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Period 
Screening 
Admission 
to Unit 
Treat
ment 
Follow-up 
Day 
-28 to -1 
-1 
D1 a 
D2 
D3 
D4 
D5 
D8 
D
15 
D
22 
D
29 
D
43 
D
57 
D
71 
D
85  
D113 
/ 
EOS 
b 
Safety 
Follow-up 
Visit c 
Visit Window (day) 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
-- 
± 
1 
± 
1 
± 
1 
± 
2 
± 
2 
± 
2 
± 
2 
± 2 
± 3 
Prior/Concomitant 
medications review  
X 
Adverse event review l 
X 
Laboratory Assessments 
Hematology m 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
Clinical chemistry m 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
Coagulation m 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
IgG to SARS-CoV-2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
rRT-PCR test for 
COVID-19 
(nasopharyngeal or 
oropharyngeal swab) 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Urinalysis n 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
X 
Alcohol/drugs screen o 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PK and ADA blood 
sampling 
 
 
See Appendix 3  
 
Hepatitis B and 
C testing 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test (if 
applicable) p 
X 
X 
 
 
 
 
 
 
 
X 
 
X 
 
X 
X 
 
HIV test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Abbreviations: ADA, antidrug antibody; AEs, adverse events; COVID-19, Coronavirus Disease 2019; D, day; ECG, electrocardiogram; EOS, End-of-Study; 
HIV, human immunodeficiency virus; Ig, immunoglobulin; IRT, Interactive Response Technology; PK, pharmacokinetic; rRT-PCR, real-time reverse 
transcription-polymerase chain reaction; SAEs, serious adverse events.  
a  The schedule of assessments for Day 1 under different timepoints are provided in Appendix 2. 
b  The EOS Visit will be conducted within 7 days after a premature study discontinuation. The Day 113 Visit is the EOS Visit for subjects who complete all the 
previously planned study visits. 
c  The Safety Follow-up Visit is only for subjects who discontinue the study within 30 days after the dose of study drug. The Safety Follow-up Visit will be 
conducted on 30 days after the dose of study drug (± 3 days). If the premature discontinuation from study occurs within 7 days prior to the timepoint of 
30 days after the dose of study drug, the Safety Follow-up Visit could be combined with the EOS Visit as appropriate.  
d  The informed consent must be obtained before performing any study-specific procedures. Consent must be obtained using the current version of the form 
approved by the Independent Ethics Committee/Institutional Review Board. 
e   Follicle-stimulating hormone and estradiol assessments will be performed on female subjects who are < 55 years of age with no spontaneous menses for 
≥ 12 months to identify the status of no childbearing potential. Female subjects of no childbearing potential, and female subjects of childbearing potential 
who are willing to use a highly effective method of birth control are eligible to participate. 
f  Subjects will be randomized into either the active arm or control arm via IRT. Randomization will occur after the admission on Day -1 and before the dose of 
study drug on Day 1. 
g  The dose will be based on the subject’s actual body weight on the day of receiving the study drug (Day 1). 
h  Height and weight will be measured at screening, and weight will be measured again before the single dose of study drug on Day 1.  
i  Complete physical examination includes evaluations of 1) head, eyes, ears, nose, and throat; 2) cardiovascular; 3) dermatological; 4) musculoskeletal; 
5) respiratory; 6) gastrointestinal; and 7) neurological systems. At subsequent visits (and as clinically indicated), limited, symptom-directed physical 
examinations will be performed.   
j  At each timepoint, 3 consecutive 12-lead ECGs will be performed approximately 2 minutes apart to calculate heart rate and measure QT and QTcF intervals. 
k  The cardiac telemetry will be performed from approximately 1 hour predose to 24 hours post dosing. 
l  After informed consent has been signed but prior to the administration of the study drug, only SAEs should be reported. After initiation of the study drug, all 
AEs and SAEs, regardless of relationship to study drug, will be reported until 30 days after the dose of study drug or EOS Visit, whichever is later. After the 
period, the investigator should report any SAEs that are considered to be related to the study drug. 
m  Hematology, clinical chemistry and coagulation will be evaluated by a local laboratory. The list of hematology, clinical chemistry and coagulation parameters 
is provided in Appendix 4. 
n  Collect sample for urine analysis as well as urine microscopy. The urine microscopy will be performed if the urinalysis parameter, such as leukocyte esterase, 
is out of normal range.  
o  During the screening, a urine sample will be collected for the screening of drugs; a breath test will be performed for the screening of alcohol. 
p   Pregnancy test will be performed for female subjects of childbearing potential during the study. The serum pregnancy test will be performed at the Screening 
Visit, and the next serum pregnancy test will be conducted after the admission on Day -1 and before the dose of study drug on Day 1. Female subjects of 
childbearing potential with negative results will be eligible to receive the study drug. Afterwards, urine pregnancy test will be performed. A serum pregnancy 
test must be performed if the urine pregnancy test is positive or equivocal. 
 
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APPENDIX 2. SCHEDULE OF ASSESSMENTS FOR DAY 1 
Study Day 
Day 1 
Timepoint 
(Window Period) 
Predose 
Dosing 
1-hour postdose 
6-hours postdose 
12-hours postdose 
BGB-DXP593 single 
dose administration 
 
X 
 
 
 
Vital signs/ 
height and weight 
X 
(- 15 min) 
 
X 
(± 15 min) 
X 
(± 15 min) 
X 
(± 15 min) 
Targeted 
physical examination 
X 
(- 30 min) 
 
 
 
 
12-lead ECG 
X 
(- 15 min) 
 
X 
(± 15 min) 
X 
(± 15 min) 
X 
(± 15 min) 
Cardiac telemetry 
X 
Prior/Concomitant 
medications review  
X 
Adverse event review 
X 
Hematology 
X 
(- 60 min) 
 
 
 
 
Clinical chemistry 
X 
(- 60 min) 
 
 
 
 
Coagulation 
X 
(- 60 min) 
 
 
 
 
Urinalysis 
X 
(- 60 min) 
 
 
 
 
Abbreviations: ECG, electrocardiogram; min, minutes. 
 
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APPENDIX 3. PHARMACOKINETIC AND ANTIDRUG ANTIBODY BLOOD SAMPLING 
Study Day 
 
Day 1 
 
Day 
2 
Day 
3 
Day 
4 
Day 
5 
Day 
8 
Day 
15 
Day 
22 
Day 
29 
Day 
43 
Day 
57 
Day 
71 
Day 
85 
Day 
113/
EOS 
Hours post the 
start of infusion 
0 
(predose) 
EOI 
 
6 
24 
48 
72 
96 
168 
336 
504 
672 
1008 
1344 
1680 
2016 
2688 
Window Period 
(hours) 
-60 min 
to 
predose 
Within 
30 min 
after 
EOI 
±2 
±6 
±6 
±6 
±6 
±6 
±24 
±24 
±24 
±48 
±48 
±48 
±48 
±48 
PK blood 
sampling 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ADA sampling 
X 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
X 
X 
Abbreviations:  ADA, antidrug antibody; EOI, end of infusion; EOS, End-of-Study; min, minutes; PK, pharmacokinetics. 
Note: Sample collection must be from the opposite arm that is used for study drug infusion. Refer to laboratory manual for detailed collection instructions. 
 
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APPENDIX 4. CLINICAL LABORATORY ASSESSMENTS 
Clinical chemistry 
Hematology 
Coagulation 
Urinalysis a 
Alkaline phosphatase 
Alanine aminotransferase 
Aspartate aminotransferase 
Albumin 
Total bilirubin 
Direct bilirubin 
Blood urea nitrogen or urea 
Potassium 
Sodium 
Total calcium 
Creatinine 
Glucose 
Lactate dehydrogenase 
Total protein 
Magnesium 
Lipase 
Amylase 
Red blood cell count 
Hematocrit 
Hemoglobin 
Platelet count 
White blood cell count with 
differential (both absolute 
count and percentage) 
• 
Lymphocyte count 
• 
Neutrophils 
• 
Monocytes 
• 
Eosinophils 
• 
Basophils 
Prothrombin time 
Partial thromboplastin 
time or activated partial 
thromboplastin time 
International 
normalized ratio 
Specific gravity 
pH 
Glucose 
Protein 
Blood 
Ketones 
Bilirubin 
Urobilinogen  
Nitrite 
Leukocyte esterase 
Other Screening Tests 
• 
Follicle-stimulating hormone and estradiol (as needed for female subjects who are < 55 years of age with no 
spontaneous menses for ≥ 12 months to identify the status of no childbearing potential) 
• 
Urine (drugs screen [to include at minimum: amphetamines, barbiturates, benzodiazepines , cocaine, opiates, 
methamphetamines, methadone, methyl enedioxy methamphetamine, phencyclidine, and 
tetrahydrocannabinol]) 
• 
Breath test (alcohol screen) 
• 
Highly sensitive (serum/urine) human chorionic gonadotropin pregnancy test (as needed in female subjects of 
childbearing potential) 
• 
Serology: 
- 
HIV antibody 
- 
hepatitis B surface antigen, hepatitis B core antibody, hepatitis C virus antibody 
- 
IgG antibodies against SARS-CoV-2 
• 
Virology: nasopharyngeal or oropharyngeal swab for COVID-19 rRT-PCR test 
The results of each test must be entered into the CRF. 
Abbreviations: COVID-19, Coronavirus Disease 2019; CRF, case report form; HIV, human immunodeficiency 
virus; Ig, immunoglobin; pH, negative of the logarithm to base 10 of the activity of the (solvated) hydronium ion; 
rRT-PCR, real-time reverse transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory 
syndrome coronavirus 2. 
a  The urine microscopy will be performed if the urinalysis parameter, such as leukocyte esterase, is out of normal 
range. 
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APPENDIX 5. CONTRACEPTION GUIDELINES AND DEFINITIONS 
OF “WOMEN OF CHILDBEARING POTENTIAL”, “NO 
CHILDBEARING POTENTIAL” 
Contraception Guidelines 
The Clinical Trials Facilitation Group’s recommendations related to contraception and 
pregnancy testing in clinical trials include the use of highly effective forms of birth control 
(Clinical Trials Facilitation Group 2014). These methods include the following: 
• Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with the inhibition of ovulation 
− Oral, intravaginal, or transdermal 
• Progestogen-only hormonal contraception associated with the inhibition of ovulation: 
− Oral, injectable, or implantable 
Note: Oral birth control pills are not considered a highly effective form of birth 
control, and if they are selected, they must be used with a second, barrier method 
of contraception such as condoms with or without spermicide. 
• Intrauterine device 
• Intrauterine hormone-releasing system 
• Bilateral tubal occlusion 
• Vasectomized male partner 
Note: This is only considered a highly effective form of birth control when the 
vasectomized partner is the sole partner of the study participant and there has been a 
medical assessment confirming surgical success. 
− A sterile male is one for azoospermia has been demonstrated in a semen sample 
examination as definitive evidence of infertility. 
• Sexual abstinence (defined as refraining from heterosexual intercourse during the entire 
period of exposure associated with the study treatment).  
NOTE: Total sexual abstinence should only be used as a contraceptive method if it is in 
line with the subject’s usual and preferred lifestyle. Periodic abstinence (eg, calendar, 
ovulation, symptothermal, or postovulation methods), declaration of abstinence for the 
duration of exposure to study drug(s), and withdrawal are not acceptable methods of 
contraception. 
Of note, barrier contraception (including male and female condoms with or without spermicide) 
is not considered a highly effective method of contraception and if used, this method must be 
combined with another acceptable method listed above. 
Definitions of “Women of Childbearing Potential,” “Women of No Childbearing Potential” 
As defined in this protocol, “women of childbearing potential” are female subjects who are 
physiologically capable of becoming pregnant. 
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Conversely, “women of no childbearing potential” are defined as female subjects meeting any of 
the following criteria: 
• Surgically sterile (ie, through bilateral salpingectomy, bilateral oophorectomy, or 
hysterectomy) 
• Postmenopausal, defined as: 
− ≥ 55 years of age with no spontaneous menses for ≥ 12 months OR 
− < 55 years of age with no spontaneous menses for ≥ 12 months AND with a 
postmenopausal follicle-stimulating hormone (FSH) concentration > 30 IU/mL 
and all alternative medical causes for the lack of spontaneous menses for 
≥ 12 months have been ruled out, such as polycystic ovarian syndrome, 
hyperprolactinemia, etc. 
If an FSH measurement is required to confirm postmenopausal state, concomitant use of 
hormonal contraception or hormonal replacement therapy should be excluded. 
Adapted from Clinical Trials Facilitation Group 2014. 
 
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STATISTICAL ANALYSIS PLAN
Study Protocol Number:
BGB-DXP593-101
Study Protocol Title:
A First-in-Human, Randomized, Double-Blind, Placebo-Controlled, 
Single Dose Escalation Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, and Immunogenicity of SARS-CoV-2
Neutralizing Antibody BGB-DXP593 in Healthy Subjects
Date:
12 May 2021
Version:
1.0
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TABLE OF CONTENTS
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS..................................................5 
1. ................ INTRODUCTION ........................................................................................................6 
2. ................ STUDY OVERVIEW...................................................................................................6 
3. ................ STUDY OBJECTIVES ................................................................................................6 
3.1. ............. Primary Objective.........................................................................................................6 
3.2. ............. Secondary Objectives ...................................................................................................7 
4. ................ STUDY ENDPOINTS..................................................................................................7 
4.1. ............. Primary Endpoint..........................................................................................................7 
4.2. ............. Secondary Endpoints ....................................................................................................7 
5. ................ SAMPLE SIZE CONSIDERATIONS .........................................................................7 
6. ................ STATISTICAL METHODS.........................................................................................7 
6.1. ............. Analysis Sets.................................................................................................................7 
6.2. ............. Data Analysis General Considerations .........................................................................8 
6.2.1. .......... Definitions and Computations ......................................................................................8 
6.2.2. .......... Conventions..................................................................................................................8 
6.2.3. .......... Handling of Missing Data.............................................................................................9 
6.2.4. .......... Multiplicity Adjustment................................................................................................9 
6.2.5. .......... Data Integrity................................................................................................................9 
6.3. ............. Subject Characteristics..................................................................................................9 
6.3.1. .......... Subject Disposition.......................................................................................................9 
6.3.2. .......... Protocol Deviations ......................................................................................................9 
6.3.3. .......... Demographic and Other Baseline Characteristics ......................................................10 
6.3.4. .......... Prior and Concomitant Medications ...........................................................................10 
6.3.5. .......... Medical History ..........................................................................................................10 
6.4. ............. Efficacy Analysis........................................................................................................10 
6.5. ............. Safety Analyses ..........................................................................................................10 
6.5.1. .......... Extent of Exposure .....................................................................................................10 
6.5.2. .......... Adverse Events ...........................................................................................................11 
6.5.3. .......... Laboratory Values ......................................................................................................11 
6.5.4. .......... Vital Signs ..................................................................................................................12 
6.5.5. .......... Electrocardiograms (ECG) .........................................................................................12 
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6.6. ............. Pharmacokinetic Analyses..........................................................................................12 
6.6.1. .......... Calculation of Serum Pharmacokinetic Parameters ...................................................12 
6.6.2. .......... Reporting of Pharmacokinetic Concentrations for Descriptive Statistics ..................13 
6.6.3. .......... Plots of Pharmacokinetic concentrations....................................................................14 
6.6.4. .......... Reporting of PK Parameters for Descriptive Statistics...............................................14 
6.6.5. .......... Software......................................................................................................................14 
6.7. ............. Immunogenicity Analyses ..........................................................................................15 
7. ................ INTERIM ANALYSIS...............................................................................................15 
8. ................ CHANGES IN THE PLANNED ANALYSIS...........................................................15 
9. ................ REFERENCES ...........................................................................................................16 
APPENDIX A. IMPUTATION OF MISSING OR PARTIALLY MISSING DATES..............17 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS
Abbreviation
Definition
ADA
Antidrug antibody
AE
Adverse event
ATC
Anatomical Therapeutic Chemical
AUC
Area under the concentration-time curve
BGB-DXP593
Code name for monoclonal antibody BGB-DXP593, also named DXP593, 
BD-368-2, and WBP2281
BLQ
Below the assay quantification limit
BMI
Body mass index
CL
Clearance
Cmax
Maximum observed concentration
CV
Coefficient of variance
ECG
Electrocardiogram
eCRF
Electronic case report form
LLOQ
Lower limit of quantitation
MedDRA®
Medical Dictionary for Regulatory Activities
NAb
Neutralizing antibody
NCI-CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
PK
Pharmacokinetic 
PT
Preferred term
SAE
Serious adverse event
SAP
statistical analysis plan
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SMC
Safety Monitoring Committee
SOC
System organ class
SD
Standard deviation
TEAE
Treatment-emergent adverse event
t1/2
Terminal half-life
tmax
Time to maximum observed concentration 
VZ
Volume of distribution
WHO DD
World Health Organization Drug Dictionary
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1.
INTRODUCTION
The purpose of this statistical analysis plan (SAP) is to describe the procedures and the statistical 
methods that will be used to analyze and report results for BGB-DXP593-101, A First-in-
Human, Randomized, Double-Blind, Placebo-Controlled, Single Dose Escalation Study to 
Evaluate the Safety, Tolerability, Pharmacokinetics, and Immunogenicity of SARS-CoV-2
Neutralizing Antibody BGB-DXP593 in Healthy Subjects. The focus of this SAP is for the 
planned final analysis specified in the study protocol.
Reference materials for this statistical plan include the BGB-DXP593-101 Original Protocol 
dated on 04 August 2020.
2.
STUDY OVERVIEW
This is a first-in-human, randomized, double-blind, placebo-controlled, single dose escalation 
study to investigate the safety, tolerability, pharmacokinetic (PK), and immunogenicity of BGB-
DXP593 in healthy subjects.
Two dose levels are planned for eligible subjects to receive a single intravenous dose of study 
drug (ie, BGB-DXP593 or placebo) at 10 mg/kg or 30 mg/kg, respectively. Another higher dose 
level will be allowed for dose escalation. 
Enrollment will begin at the 10 mg/kg dose level. Escalation to the next dose level will occur 
7 days after the last subject at the current dose level has received the study drug, and the safety, 
laboratory data have been reviewed. 
At each dose level, eligible subjects will be randomized at a 3:1 ratio (6 active: 2 control) to the
active arm for receiving BGB-DXP593 or to the control arm for receiving the same volume of 
placebo (ie, normal saline), respectively.
The sentinel dosing will be adopted for each dose level. In the other words, 2 eligible subjects 
will be randomized at a 1:1 ratio (1 active: 1 control) to receive BGB-DXP593 or placebo on 
Day 1; and the remaining subjects will be randomized at a 5:1 ratio (5 active: 1 control) to 
receive BGB-DXP593 or placebo at least 48 hours later, provided satisfactory safety and 
tolerability is demonstrated for the first 2 subjects randomized and dosed at the dose level.
Subjects are expected to be available for follow-up visits until Day 113 of the study. Subjects 
will be replaced if they cannot complete the infusion. Subjects may be replaced if they 
discontinue from the study before Day 29.
Subjects will be monitored for safety, tolerability, PK and immunogenicity of BGB-DXP593 
throughout the study.
3.
STUDY OBJECTIVES
3.1.
Primary Objective
x
To investigate the safety and tolerability of BGB-DXP593 administered intravenously 
as a single dose in healthy subjects
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3.2.
Secondary Objectives
x
To characterize the pharmacokinetic (PK) profile of BGB-DXP593 administered 
intravenously as a single dose at each dose level in healthy subjects
x
To evaluate the potential immunogenicity of BGB-DXP593 administered 
intravenously as a single dose at each dose level in healthy subjects  
4.
STUDY ENDPOINTS
4.1.
Primary Endpoint
x
Incidence and severity of treatment-emergent adverse events (TEAEs) and 
treatment-emergent serious adverse events (SAEs)
4.2.
Secondary Endpoints
x
Changes in vital signs and 12-lead electrocardiogram (ECG) parameters from 
baseline
x
Incidence and magnitude of clinical laboratory abnormalities
x
Characterize PK concentration-time profile and PK parameters for BGB-DXP593:
Cmax, AUCt, AUCinf, AUC0-29, tmax, t1/2, CL, and Vz as appropriate
x
Clinical immunogenicity of BGB-DXP593 evaluated through the detection of ADA 
over time
5.
SAMPLE SIZE CONSIDERATIONS
A sample size of 8 subjects at each dose level (6 active and 2 control) totaling up to 30 subjects 
(including possible replacement) is not based on any statistical considerations.  The sample size 
is based on the clinical consideration to provide safety and tolerability information and 
pharmacological considerations with the need to minimize exposure to healthy subjects at each 
dose level.  No formal inferential statistics will be applied to the safety or PK data.
6.
STATISTICAL METHODS
6.1.
Analysis Sets
The Safety Analysis Set will include all the subjects who received the study drug, and subjects 
will be grouped by actual treatment received. The Safety Analysis Set is used for all safety 
analyses.
The PK Analysis Set will include all the subjects who received the study drug and had any 
measurable concentration of study drug. The PK Analysis Set will be used for PK analyses.
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The ADA Analysis Set include all the subjects who received the study drug and in whom both 
baseline ADA and at least 1 postbaseline ADA results are available. The ADA Analysis Set is 
used for immunogenicity analyses.
6.2.
Data Analysis General Considerations
6.2.1.
Definitions and Computations
Study Day: study day will be calculated in reference to the date of the dose of study drug. For 
assessments conducted on or after the date of the dose of study drug, study day will be calculated 
as (assessment date – the date of the dose of study drug + 1). For assessments conducted before 
the date of the dose of study drug, study day will be calculated as (assessment date – the date of 
the dose of study drug). There is no study day 0.
In the situation where the event date is partial or missing, the date will appear partial or missing 
in the listings. Study day and any corresponding durations will be presented based on the 
imputations specified in Appendix A.
Baseline: baseline is defined as the last non-missing value collected before the dose of study 
drug.
All calculations and analyses will be conducted using SAS® Version 9.4 or higher.
All subjects who received placebo from different cohorts will be pooled together into the placebo 
arm.
6.2.2.
Conventions
Unless otherwise specified, the following conventions will be applied to all analyses:
x
1 year = 365.25 days. Number of years is calculated as (days/365.25) rounded up to 1 
significant digit.
x
1 month = 30.4375 days. Number of months is calculated as (days/30.4375) rounded 
up to 1 significant digit.
x
Age will be calculated as the integer part of (date of informed consent – date of birth 
+ 1)/365.25.
x
P-values will be rounded to 4 decimal places. P-values that round to 0.0000 will be 
presented as '< 0.0001' and p-values that round to 1.000 will be presented as 
'> 0.9999'. 
x
For laboratory results collected as  x, the value of the laboratory results will be set as 
x. For laboratory results collected as < x, the value of the laboratory results will be set 
as x divided by 2.
x
For by-visit observed data analyses, percentages will be calculated based on the
number of subjects with non-missing data as the denominator, unless otherwise 
specified.
x
Unscheduled measurements and retested measurements will not be included in by-
visit table summaries and graphs but will contribute to the best/worst case value 
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where required (e.g., shift table). Listings will include scheduled, unscheduled and 
retest data.
x
For continuous endpoints, summary statistics will include n, mean, standard 
deviation, median, Q1, Q3 and range (minimum and maximum).
x
For discrete endpoints, summary statistics will include frequencies and percentages.
6.2.3.
Handling of Missing Data
Missing data will not be imputed unless otherwise specified elsewhere in this SAP. Missing 
dates or partially missing dates will be imputed conservatively for adverse events and 
prior/concomitant medications/procedures. Specific rules for the handling of missing or partially 
missing dates for adverse events and prior/concomitant medications/procedures are provided in 
Appendix A.
By-visit endpoints will be analyzed using observed data unless otherwise specified. For observed 
data analyses, missing data will not be imputed, and only the observed records will be included.
6.2.4.
Multiplicity Adjustment
No multiplicity adjustments will be made in this study.
6.2.5.
Data Integrity
Before pre-specified final analysis begins, the integrity of the data should be reviewed to assure 
fit-for-purpose. The data set for analysis should be an accurate and complete representation of 
the subjects' relevant outcomes from the clinical database. All data should be complete and 
reviewed up to a pre-specified cutoff date as specified in the Data Extract and Snapshot Plan.
Consistency checks and appropriate source data verification should be completed as specified in 
the Site Monitoring Plan.
6.3.
Subject Characteristics
6.3.1.
Subject Disposition
The number (percentage) of subjects randomized, treated, discontinued from the study drug 
and/or study will be counted by dose level. The primary reason for subjects randomized but not 
treated and study drug and/or study discontinuation will be summarized according to the 
categories in the eCRF. A listing of subject disposition will be provided.
6.3.2.
Protocol Deviations
Important protocol deviation criteria will be established, and subjects with important protocol 
deviations will be identified and documented. 
Important protocol deviations will be summarized and listed by category for all subjects in the
Safety Analysis Set. Deviation categories are not mutually exclusive. Multiple deviations within 
the same category are counted once per subject.
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6.3.3.
Demographic and Other Baseline Characteristics
Demographics and other baseline characteristics will be summarized by dose level using 
descriptive statistics in the Safety Analysis Set. Summary statistics will be presented for 
continuous variables, and the number (percentage) of subjects in each category will be presented 
for categorical variables. Continuous variables include but are not limited to age, height, weight, 
and body mass index (BMI). Categorical variables include but are not limited to sex, race, and 
ethnicity. A listing of demographics and other baseline characteristics will be provided.
6.3.4.
Prior and Concomitant Medications
Prior medications will be defined as medications that started and stopped before the dose of 
study drug.  Concomitant medications will be defined as medications that (1) started before the 
dose of study drug and were continuing at the time of the dose of study drug, or (2) started on or 
after the date of the dose of study drug up to 30 days after the dose of study drug.
Prior and concomitant medications will be coded using the version of World Health Organization 
Drug Dictionary (WHO DD) drug codes currently in effect at BeiGene at the time of database 
lock. They will be further coded to the appropriate Anatomical Therapeutic Chemical (ATC)
code indicating therapeutic classification.
The number (percentage) of subjects reporting prior and concomitant medications will be 
summarized by ATC medication class and WHO DD preferred name in the Safety Analysis Set. 
A listing of prior and concomitant medications will be provided.
6.3.5.
Medical History
Medical History will be coded using Medical Dictionary for Regulatory Activities (MedDRA) 
version currently in effect at BeiGene at the time of database lock. The number (percentage) of 
subjects reporting a history of any medical condition, as recorded on the CRF, will be 
summarized by system organ class (SOC) and preferred term (PT) in the Safety Analysis Set. A
listing of medical history will be provided.
6.4.
Efficacy Analysis
There is no efficacy analysis planned for this study.
6.5.
Safety Analyses
All safety analyses will be performed based on the Safety Analysis Set.  Descriptive statistics 
will be used to analyze all safety data.
6.5.1.
Extent of Exposure
The extent of study drug exposure will be summarized descriptively for the single dose 
administered by dose level. The number (percentage) of subjects with dose interruption and 
infusion rate decreased will be summarized with the respective reasons by dose level.
Subject data listings will be provided for all dosing records.
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6.5.2.
Adverse Events 
The AE verbatim descriptions (investigator terms from the eCRF) will be classified into 
standardized medical terminology using MedDRA.  Adverse events will be coded to the
MedDRA lowest level term closest to the verbatim term, along with the linked MedDRA PT and 
primary SOC.
A TEAE is defined as an AE that had an onset date or a worsening in severity from baseline on 
or after the administration of study drug and up to 30 days after the dose of study drug. Summary 
tables will generally focus on those AEs that were treatment-emergent. All AEs, treatment-
emergent or otherwise, will be presented in subject data listings.
If any of the following TEAEs occurs, the administration of the study drug and the enrollment of 
new subjects will pause for the dose level:
x
One or more  Grade 4 TEAEs or treatment-emergent SAEs related to study drug as 
assessed by the investigator in any subject or
x
Grade 3 TEAEs related to study drug as assessed by the investigator in 2 or more 
subjects at the same dose level.
An AE overview table, including the number of subjects with TEAEs, TEAEs with grade 3, 
TEAEs with grade 4 or higher, treatment-emergent SAEs, TEAEs that led to death, TEAEs that 
led to treatment discontinuation, TEAEs that led to treatment modification for study drug, and 
treatment-related TEAEs, will be provided by dose level. Treatment-related AEs include those 
events considered by the investigator to be related to study drug or with a missing assessment of 
the causal relationship.
The incidence of TEAEs will be reported as the number (percentage) of subjects with TEAEs by 
SOC, PT and the worst grade. A subject will be counted only once by the highest severity grade 
according to NCI-CTCAE version 5.0 within a SOC and PT, even if the subject experienced 
more than one TEAE within a specific SOC and PT. The number (percentage) of subjects with
treatment-emergent SAEs will be summarized by SOC and PT.
6.5.3.
Laboratory Values
Clinical laboratory values will be evaluated for each laboratory parameter as appropriate.
Descriptive summary statistics (n, mean, standard deviation, median, Q1, Q3, minimum, and 
maximum for continuous variables; n [%] for categorical variables) for laboratory parameters and 
their changes from baseline will be summarized by visit and dose level. Change from baseline will 
only be summarized for subjects with both baseline and postbaseline measurements.
Laboratory parameters that are graded in NCI-CTCAE v5.0 will be summarized by shifts from 
baseline CTCAE grades to maximum postbaseline grades. In the summary of laboratory 
parameters by CTCAE grade, parameters with CTCAE grading in both high and low directions 
will be summarized separately.
Subject data listings of each parameter will be provided. Abnormal values will be flagged and 
identified as those outside (above or below) the normal range.
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6.5.4.
Vital Signs
Descriptive statistics for vital sign parameters (systolic and diastolic blood pressure, pulse rate, 
respiratory rate, and body temperature) and changes from baseline will be summarized by visit 
and dose level.
Subject data listings of each parameter will be provided. Abnormal values will be flagged and 
identified as those outside (above or below) the normal range. Reference (normal) ranges for 
vital signs parameters are defined as following:
x
Respiratory rate: 10-22 bpm 
x
Temperature: 35.5-37.5 °C
x
Systolic blood pressure: 90-140 mmHg
x
Diastolic blood pressure: 40-90 mmHg
x
Pulse rate: 60-100 bpm
6.5.5.
Electrocardiograms (ECG)
Descriptive statistics for ECG parameters (heart rate and QTcF interval) and changes from 
baseline will be summarized by visit and dose level.
Subject data listings of each parameter will be provided. Abnormal values will be flagged and 
identified as those outside (above or below) the normal range. Reference (normal) ranges for 
ECG parameters are defined as following:
x
Heart rate: 60-100 bpm
x
QTcF interval: 450 msec
6.6.
Pharmacokinetic Analyses
The following analysis plan provides the framework for the summarization of the PK data. The 
objective is to assess BGB-DXP593 PK and characterize PK parameters following a single
intravenous dose. The PK analyses will include only subjects randomized to receive 
BGB-DXP593 and with enough data to enable estimation of key parameters. Additional PK 
analyses (such as modeling and simulation using nonlinear mixed effects modelling) may be 
conducted if deemed necessary and will be described in a separate analysis plan.
6.6.1.
Calculation of Serum Pharmacokinetic Parameters
Actual dose and blood draw times will be used to calculate the PK parameters. Parameters will 
be listed individually and summarized by dose level using descriptive statistics.
The following plasma PK parameters will be calculated for BGB-DXP593, as appropriate for the 
data collected. Other PK parameters may be calculated if supported by the data.
Calculation and presentation of PK parameters will be based on the Work Instruction: Best Practice 
Guidance: Non-Compartmental Pharmacokinetic Data Analysis for Clinical Studies. Version 1.0,
Document Number VV-QDOC-13140.
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Parameter 
(Units)
Definition
Method of Determination
AUC0-29
(ȝg·day/mL)
Area under the serum concentration 
versus time curve from Day 1 to Day 29
Calculated using the linear up/log down variant 
of the trapezoidal rule
AUCinf
(ȝg·day/mL)
AUC from zero to infinite time with 
extrapolation of the terminal phase
Calculated using the linear up/log down variant 
of the trapezoidal rule
AUC0-8
(ȝg·day/mL)
Area under the serum concentration 
versus time curve from Day 1 to Day 8
Calculated using the linear up/log down variant 
of the trapezoidal rule
AUC0-15
(ȝg·day/mL)
Area under the serum concentration 
versus time curve from Day 1 to Day 15
Calculated using the linear up/log down variant 
of the trapezoidal rule
AUClast
(ȝg·day/mL)
AUC from time zero to time of last 
quantifiable concentration
Calculated using the linear up/log down variant 
of the trapezoidal rule
Cmax (ȝg/mL)
Maximum observed drug concentration 
during a dosing interval
Reported value
tmax (h)
Time to reach Cmax
Actual elapsed time for reported Cmax
t1/2 (days)
half-life
ln(2)/Ȝz, where Ȝz is the first-order rate constant 
of drug associated with the terminal portion of 
the curve
CL (L/h)
clearance
Calculated as Dose/AUCinf
Vz (L)
volume of distribution during the 
terminal phase
Calculated as CL/Ȝz, where Ȝz is the first-order 
rate constant of drug associated with the 
terminal portion of the curve
6.6.2.
Reporting of Pharmacokinetic Concentrations for Descriptive Statistics
The PK analyst will appropriately flag and annotate treatment of any anomalous concentrations,
exclusions and any special treatment for descriptive statistics and plots. BGB-DXP593 
concentration and time data will be listed individually and summarized by dose level using 
descriptive statistics.
The following conventions will be used for reporting descriptive statistics for concentration data.
x
PK concentrations should be reported in listings at the same level of precision as that 
in the source data.
x
If a concentration at a given time point is below the assay quantification limit (BLQ), 
the concentration shall be reported as the term “BLQ” with the lower limit of 
quantitation (LLOQ) defined in the footnotes. BLQ values shall be treated as zero for 
computation of descriptive statistics.
x
If a concentration at a given time point is missing it shall be reported as a missing 
value. Missing values may be defined in a bioanalytical source as “NS” (no sample),
“NR” (no result), “IS” (insufficient sample), etc. If missing data are not identified in 
the bioanalytical source (i.e., the record is missing), the reporting convention of “NS" 
shall be utilized.
x
If the calculated mean concentration is BLQ, the mean value shall be reported in 
outputs (such as tables) as BLQ and SD and CV% shall be reported as ND (not 
determined). Minimum, median, and maximum may be reported. 
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6.6.3.
Plots of Pharmacokinetic concentrations
BGB-DXP593 concentration versus time data will be plotted individually and summarized 
graphically using arithmetic mean (±SD) plots by dose level. Arithmetic mean concentrations 
that are BLQ shall be set to zero for plotting on both linear scale and log-linear scale.
6.6.4.
Reporting of PK Parameters for Descriptive Statistics
The PK analyst will appropriately flag and annotate treatment of any anomalous PK parameters,
exclusions and any special treatment for descriptive statistics.
x
All the PK parameters except tmax should have at least the following summary 
statistics: sample size (n), mean, standard deviation (SD), coefficient of variance 
(CV%), median, minimum, maximum, geometric mean, geometric CV%; tmax  should 
be presented as median, range (minimum, maximum) , and sample size (n) when 
presenting the summary statistics.
x
Geometric mean (geometric CV%) will be the default method of reporting PK 
parameters within in-text tables.
x
For any parameters that n  2, SD should not be presented.
x
The units for all PK parameters will be provided.
x
It is recognized that the number of decimals in reported concentrations, for example:
“9632.94401 ng/mL” or “9.963294401 ug/mL" are highly improbable and will be 
queried (since bioanalytical assays generally do not have this level of precision).
Usually the first-in-human dose escalation trial will provide the numerical range of 
PK parameters e.g. AUC range from 10 to 10,000 ng.hr/mL and Cmax range from 1 to 
1000 ng/mL.  
In this scenario, for reporting PK parameters such as AUC and Cmax, the following 
guidance is provided for rounding: 

If the numerical value is below 100 then one decimal place may be used e.g. 0.1 
or 99.9

For values ranging from >100, whole numbers should be used e.g. 100 or 9999. 

If > 10,000 the clinical pharmacologist may decide on changing units e.g. from 
ȝg/ml to mg/ml.

For reporting times e.g. for tmax or t1/2, if <1 hr use 2 decimals; time up to 24 hr 
should be reported to one decimal place e.g. 23.5 hr, time >24 hr should be 
rounded to nearest whole number e.g. 105 hr.
6.6.5.
Software 
For the calculations of PK parameters Phoenix® WinNonlin® Version 7.0 or higher (Certara, 
NJ. USA) will be used.
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6.7.
Immunogenicity Analyses
The scope of anti-drug antibodies (ADA) calculations used for characterizing clinical 
immunogenicity depends on the incidence and kinetics of detected (ADA). Therefore, not all 
parameters described below may be derived.
The immunogenicity results will be summarized using descriptive statistics by the number and 
percentage of subjects who develop detectable ADAs. The incidence of positive and neutralizing 
ADAs will be reported for ADA-evaluable subjects according to the following definitions:
x
ADA-evaluable subject: Number of subjects with reportable non-missing baseline result 
and at least one reportable sample taken after drug administration during the treatment or 
follow-up observation period with reportable result (used for computing treatment-
induced ADA incidence).
x
Treatment-emergent ADA: Treatment-boosted ADA subject or treatment-induced ADA 
subject. Synonymous with “ADA Incidence”.
x
Treatment-induced ADA: ADA-evaluable subjects that were ADA-negative at baseline 
and ADA-positive following administration of biologic product.
x
Treatment-boosted ADA: Baseline-positive ADA-evaluable subject with significant 
increases (4-fold or higher) in ADA titer after biologic drug administration. [Baseline-
positive ADA-evaluable subject: an ADA-evaluable subject with positive ADA result].
x
Persistent ADA: Treatment-induced ADA detected at two or more sampling time points 
during the treatment (including follow-up period if any), where the first and last ADA-
positive samples (irrespective of any negative samples in between) are separated by a 
period of 16 weeks or longer.
x
Transient ADA: Treatment-induced ADA detected only at one sampling time point 
during the treatment or follow-up observation period, or two or more time points during 
the treatment, where the first and last ADA-positive samples are separated by a period of 
less than 16 weeks, and the subject last sampling time point is ADA-negative.
x
Neutralizing ADA: subjects with positive NAb.
The immunogenicity results will also be listed.
Additional ADA analyses (such as the effect of immunogenicity on PK, and safety) may be 
conducted if deemed necessary and will be described in a separate analysis plan.
7.
INTERIM ANALYSIS
There is no formal interim analysis planned for this study.
8.
CHANGES IN THE PLANNED ANALYSIS
Not applicable.
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9.
REFERENCES
Common Terminology Criteria for Adverse Events (CTCAE).  Version 5.0.  United States 
Department of Health and Human Services, National Institutes of Health, National Cancer 
Institute, Washington, DC, USA, November 27, 2017.
Work Instruction: Best Practice Guidance: Non-Compartmental Pharmacokinetic Data Analysis 
for Clinical Studies. Version 1.0, Document Number VV-QDOC-13140.
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APPENDIX A. IMPUTATION OF MISSING OR PARTIALLY MISSING 
DATES
In general, missing or partial dates will not be imputed at the data level. The following rules will 
apply for the specific analysis and summary purposes mentioned below only.
1. Adverse Events
If AE start (onset) date or end date is missing or partial missing, the following imputation rules 
apply.  
If end date of an adverse event is partially missing, impute as follows:
•
If both month and day are missing, then set to December 31
•
If only day is missing, then set to last day of the month
•
If the imputed end date > death date, then set to death date
If year of the end date is missing or end date is completely missing, do not impute.
If start date of an adverse event is partially missing, impute as follows:
•
If both month and day are missing and year = year of treatment start date, then set to 
treatment start date
•
If both month and day are missing and year  year of treatment start date, then set to 
January 01
•
If day is missing and month and year = month and year of treatment start date, then set to 
treatment start date
•
If day is missing and month and year  month and year of treatment start date, then set to 
first of the month
•
If the imputed start date > death date, then set to death date
If year of the start date is missing or start date is completely missing, do not impute. 
If the imputed start date > the end date (or the imputed end date), set the imputed start date = end 
date (or the imputed end date). 
2. Prior/Concomitant Medications/Procedures
When the start date or end date of a medication/procedure is partially missing, the date will be 
imputed to determine whether the medication/procedure is prior or concomitant. The following 
rules will be applied to impute partial dates for medication/procedure:
If start date of a medication/procedure is partially missing, impute as follows:
•
If both month and day are missing, then set to January 01
•
If only day is missing, then set to the first of the month
•
If the imputed start date > death date, then set to death date
If end date of a medication/procedure is partially missing, impute as follows:
•
If both month and day are missing, then set to December 31
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•
If only day is missing, then set to last day of the month
•
If the imputed end date > death date, then set to death date
If the year of start date or year of end date of a medication/procedure is missing, or the start date 
or end date is completely missing, do not impute.
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