Clinical trial NCT04551898
Conditions: Covid19
Sponsor: BeiGene
Start date: 2020-12-02; Completion date: 2021-05-25
Enrollment: 181 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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

Detailed description:

Arms: arm 1: Participants will receive BGB-DXP593 on Day 1, and followed up for safety for up to 85 days arm 2: Participants will receive BGB-DXP593 on Day 1, and followed up for safety for up to 85 days arm 3: Participants will receive BGB-DXP593 on Day 1, and followed up for safety for up to 85 days arm 4: Participants will receive placebo on Day 1, and followed up for safety for up to 85 days
Interventions: intervention 1: BGB-DXP593 intervention 2: Placebo
Intervention descriptions: intervention 1: Intravenous (IV) infusion administered over 30 to 90 minutes at a dose as specified in the treatment arm intervention 2: Placebo to match BGB-DXP593 administered as specified in the treatment arm

Protocol documents:
Prot_000.pdf: 
BGB-DXP593-102  
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27 October 2020 
 
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CLINICAL STUDY PROTOCOL 
 
 
 
Protocol Title:  
A Phase 2, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Efficacy and Safety of SARS-CoV-2 
Neutralizing Antibody BGB-DXP593 in Patients With Mild to 
Moderate COVID-19 
Protocol Identifier: 
BGB-DXP593-102 
Phase: 
2 
Investigational Products: 
BGB-DXP593 
Placebo 
Proposed Indication: 
COVID-19 
Sponsor: 
BeiGene, Ltd. 
c/o BeiGene USA, Inc. 
2955 Campus Drive, Suite 200 
San Mateo, California 94403 
USA 
Sponsor Medical Monitor: 
Original Protocol Version 0.0: 
14 August 2020 
Amendment 1.0 
03 September 2020 
Amendment 2.0 
27 October 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 prior written authorization from 
BeiGene, Ltd., or one of its subsidiaries. 
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INVESTIGATOR SIGNATURE PAGE 
 
Protocol Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Efficacy and Safety of SARS-CoV-2 Neutralizing 
Antibody BGB-DXP593 in Patients With Mild to Moderate 
COVID-19 
 
Protocol Identifier: 
BGB-DXP593-102 
 
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 FIGURES .................................................................................................................... 9 
SYNOPSIS ............................................................................................................................... 10 
LIST OF ABBREVIATIONS AND TERMS ............................................................................ 14 
1. 
INTRODUCTION AND RATIONALES................................................................ 16 
1.1. 
Introduction ............................................................................................................ 16 
1.2. 
BGB-DXP593 as a SARS-CoV-2 Neutralizing Monoclonal Antibody .................... 16 
1.2.1. 
Nonclinical ............................................................................................................. 16 
1.2.2. 
Clinical Experience................................................................................................. 18 
1.3. 
Study Rationale ...................................................................................................... 18 
1.3.1. 
Rationale for Selection of BGB-DXP593 Doses ..................................................... 19 
1.3.2. 
Rationale for Pharmacokinetic Sampling ................................................................ 20 
1.3.3. 
Rationale for Biomarker Strategy ............................................................................ 21 
1.4. 
Benefit-Risk Assessment ........................................................................................ 21 
1.5. 
Study Conduct ........................................................................................................ 22 
2. 
STUDY OBJECTIVES AND ENDPOINTS ........................................................... 23 
2.1. 
Study Objectives ..................................................................................................... 23 
2.1.1. 
Primary Objective ................................................................................................... 23 
2.1.2. 
Secondary Objectives ............................................................................................. 23 
2.1.3. 
Exploratory Objective ............................................................................................. 23 
2.2. 
Study Endpoints ..................................................................................................... 23 
2.2.1. 
Primary Endpoint.................................................................................................... 23 
2.2.2. 
Secondary Endpoints .............................................................................................. 23 
2.2.3. 
Exploratory Endpoints ............................................................................................ 24 
3. 
STUDY DESIGN ................................................................................................... 25 
3.1. 
Summary of Study Design ...................................................................................... 25 
4. 
STUDY POPULATION ......................................................................................... 27 
4.1. 
Inclusion Criteria .................................................................................................... 27 
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4.2. 
Exclusion Criteria ................................................................................................... 27 
5. 
STUDY TREATMENT .......................................................................................... 30 
5.1. 
Formulation, Packaging, and Handling ................................................................... 30 
5.1.1. 
BGB-DXP593 ........................................................................................................ 30 
5.1.2. 
Placebo ................................................................................................................... 30 
5.2. 
Dosage, Administration, and Compliance ............................................................... 30 
5.3. 
Incorrect Administration ......................................................................................... 31 
5.4. 
Dose Interruption or Modification........................................................................... 31 
5.5. 
Blinding.................................................................................................................. 31 
5.5.1. 
Emergency Unblinding ........................................................................................... 32 
5.5.2. 
Inadvertent Unblinding ........................................................................................... 32 
6. 
PRIOR AND CONCOMITANT THERAPY .......................................................... 33 
6.1. 
Permitted Concomitant Medications/Procedures ..................................................... 33 
6.2. 
Prohibited Concomitant Medications/Procedures .................................................... 33 
6.3. 
Potential Interactions Between the Study Drug and Concomitant 
Medications ............................................................................................................ 33 
7. 
STUDY PERIODS, VISITS, OR PROCEDURES .................................................. 34 
7.1. 
Screening Period ..................................................................................................... 34 
7.1.1. 
Informed Consent and Screening Log ..................................................................... 34 
7.1.2. 
Patient Numbering .................................................................................................. 34 
7.2. 
Enrollment .............................................................................................................. 34 
7.2.1. 
Confirmation of Eligibility...................................................................................... 34 
7.2.2. 
Enrollment/Randomization ..................................................................................... 34 
7.3. 
Treatment ............................................................................................................... 34 
7.4. 
Follow-up Period .................................................................................................... 35 
7.4.1. 
End-of-Study Visit .................................................................................................. 35 
7.4.2. 
Safety Follow-up Visit After Premature Study Discontinuation .............................. 35 
7.4.3. 
Lost to Follow-up ................................................................................................... 35 
7.5. 
Discontinuation From Study Treatment or From the Study ..................................... 35 
7.5.1. 
Patient Discontinuation From Study Treatment ....................................................... 35 
7.5.2. 
Patient Discontinuation From the Study (End of Study for an Individual 
Patient) ................................................................................................................... 36 
7.6. 
End of Study ........................................................................................................... 36 
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8. 
STUDY ASSESSMENTS....................................................................................... 37 
8.1. 
Screening Assessments ........................................................................................... 37 
8.1.1. 
Demographic Data, Medical History, and Prior Medications ................................... 37 
8.1.2. 
Review of SARS-CoV-2 Test Result ...................................................................... 37 
8.2. 
Safety Assessments................................................................................................. 37 
8.2.1. 
Vital Signs .............................................................................................................. 37 
8.2.2. 
Physical Examinations ............................................................................................ 38 
8.2.3. 
Laboratory Safety Tests .......................................................................................... 38 
8.2.4. 
Electrocardiograms ................................................................................................. 38 
8.2.5. 
Adverse Events ....................................................................................................... 38 
8.3. 
Efficacy Assessment ............................................................................................... 39 
8.3.1. 
Viral Load .............................................................................................................. 39 
8.3.2. 
WHO 8-Point Ordinal Scale.................................................................................... 39 
8.3.3. 
COVID-19-Related Symptoms and Disease Severity .............................................. 40 
8.4. 
Pharmacokinetic Assessment and Antidrug Antibody Testing ................................. 41 
8.5. 
Biomarkers ............................................................................................................. 41 
8.6. 
Visit Windows ........................................................................................................ 42 
8.7. 
Unscheduled Visits ................................................................................................. 42 
9. 
SAFETY MONITORING AND REPORTING ....................................................... 43 
9.1. 
Risks Associated With BGB-DXP593 .................................................................... 43 
9.2. 
General Plan to Manage Safety Concerns ............................................................... 43 
9.2.1. 
Eligibility Criteria ................................................................................................... 43 
9.2.2. 
Safety Monitoring Plan ........................................................................................... 43 
9.3. 
Adverse Events ....................................................................................................... 44 
9.3.1. 
Definitions and Reporting ....................................................................................... 44 
9.3.2. 
Assessment of Severity ........................................................................................... 44 
9.3.3. 
Assessment of Causality ......................................................................................... 45 
9.3.4. 
Follow-up of Adverse Events .................................................................................. 46 
9.3.5. 
Laboratory Test Abnormalities ............................................................................... 46 
9.4. 
Definition of a Serious Adverse Event .................................................................... 47 
9.5. 
Suspected Unexpected Serious Adverse Reaction ................................................... 48 
9.6. 
Timing, Frequency, and Method of Capturing Adverse Events and Serious 
Adverse Events ....................................................................................................... 48 
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9.6.1. 
Adverse Event Recording Period ............................................................................ 48 
9.6.2. 
Reporting Serious Adverse Events .......................................................................... 48 
9.6.3. 
Eliciting Adverse Events......................................................................................... 49 
9.6.4. 
Deaths .................................................................................................................... 49 
9.6.5. 
Recording Pregnancies ........................................................................................... 49 
9.6.6. 
Expedited Reporting to Health Authorities, Investigators, Institutional 
Review Boards, and Independent Ethics Committees .............................................. 50 
9.6.7. 
Recording Infusion-Related Reactions .................................................................... 50 
9.7. 
Management of Infusion-Related Reactions and Severe Hypersensitivity................ 50 
9.7.1. 
Managing Infusion-Related Reactions .................................................................... 50 
9.7.2. 
Severe Hypersensitivity Reactions .......................................................................... 51 
10. 
STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION ................ 53 
10.1. 
Statistical Analysis ................................................................................................. 53 
10.1.1. 
Analysis Sets .......................................................................................................... 53 
10.1.2. 
Randomization Methods ......................................................................................... 53 
10.1.3. 
Patient Disposition .................................................................................................. 53 
10.1.4. 
Demographic and Other Baseline Characteristics .................................................... 53 
10.1.5. 
Prior and Concomitant Medications ........................................................................ 54 
10.2. 
Efficacy Analyses ................................................................................................... 54 
10.2.1. 
Primary Endpoint Analyses .................................................................................... 54 
10.2.2. 
Secondary Endpoint Analyses ................................................................................. 56 
10.2.3. 
Exploratory Endpoint Analyses............................................................................... 57 
10.3. 
Safety Analyses ...................................................................................................... 58 
10.3.1. 
Extent of Exposure ................................................................................................. 58 
10.3.2. 
Adverse Events ....................................................................................................... 58 
10.3.3. 
Laboratory Analyses ............................................................................................... 59 
10.3.4. 
Vital Signs .............................................................................................................. 59 
10.4. 
Pharmacokinetic Analyses ...................................................................................... 59 
10.5. 
Immunogenicity Analyses....................................................................................... 59 
10.6. 
Other Exploratory Analyses .................................................................................... 59 
10.7. 
Sample Size Consideration ..................................................................................... 60 
10.8. 
Interim Analyses ..................................................................................................... 60 
10.9. 
Missing Data Handling and Censoring Rules .......................................................... 60 
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11. 
STUDY COMMITTEES ........................................................................................ 62 
11.1. 
Independent Data Monitoring Committee ............................................................... 62 
12. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS ........................................................................................... 63 
12.1. 
Access to Information for Monitoring ..................................................................... 63 
12.2. 
Access to Information for Auditing or Inspections .................................................. 63 
13. 
QUALITY ASSURANCE AND QUALITY CONTROL ........................................ 64 
13.1. 
Regulatory Authority Approval............................................................................... 64 
13.2. 
Quality Assurance .................................................................................................. 64 
13.3. 
Study Site Inspections ............................................................................................. 64 
13.4. 
Drug Accountability ............................................................................................... 64 
14. 
ETHICS/PROTECTION OF HUMAN PATIENTS ................................................ 66 
14.1. 
Ethical Standard ..................................................................................................... 66 
14.2. 
Institutional Review Board/Independent Ethics Committee ..................................... 66 
14.2.1. 
Protocol Amendments............................................................................................. 66 
14.3. 
Informed Consent ................................................................................................... 67 
14.4. 
Patient and Data Confidentiality ............................................................................. 67 
14.5. 
Financial Disclosure ............................................................................................... 68 
15. 
DATA HANDLING AND RECORD KEEPING .................................................... 69 
15.1. 
Data Collection and Management Responsibilities .................................................. 69 
15.1.1. 
Data Entry in the Electronic Case Report Form ....................................................... 69 
15.1.2. 
Data Collection ....................................................................................................... 69 
15.1.3. 
Data Management/Coding ...................................................................................... 69 
15.2. 
Study Records Retention......................................................................................... 70 
15.3. 
Protocol Deviations ................................................................................................ 71 
15.4. 
Study Report and Publications ................................................................................ 71 
15.5. 
Study and Study Center Closure ............................................................................. 72 
15.6. 
Information Disclosure and Inventions.................................................................... 72 
16. 
REFERENCES ....................................................................................................... 74 
17. 
APPENDICES ........................................................................................................ 76 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ................................................................. 77 
APPENDIX 2. PHARMACOKINETIC AND ANTIDRUG ANTIBODY BLOOD 
SAMPLING ........................................................................................................... 81 
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APPENDIX 3. CLINICAL LABORATORY ASSESSMENTS .............................................. 82 
APPENDIX 4. CONTRACEPTION GUIDELINES AND DEFINITIONS OF 
“WOMEN OF CHILDBEARING POTENTIAL,” “NO CHILDBEARING 
POTENTIAL” ........................................................................................................ 83 
 
LIST OF TABLES 
Table 1: 
Projected Safety Margins at Proposed Doses in Humans ......................................... 20 
Table 2: 
Timeframes and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee .......................................................................... 48 
Table 3: 
Treatment Modifications for Symptoms of Infusion-Related Reactions Due 
to Study Drug ......................................................................................................... 51 
Table 4: 
Parameter(s) in Each Model .................................................................................... 55 
Table 5: 
Censoring Rules for Analysis of Time-to-event Endpoints ...................................... 61 
 
LIST OF FIGURES 
Figure 1: 
Simulated BGB-DXP593 Serum and Lung (Assuming 1% Biodistribution) 
Concentration-Time Profiles in Humans ................................................................. 20 
Figure 2: 
Study Schema ......................................................................................................... 25 
Figure 3: 
Shape of the Considered Dose Response Patterns for the MCPMod Analysis.......... 55 
 
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x 
Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse 
events (SAEs) 
x 
PK parameters: 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 Day 29 (AUC0-29), AUC from time zero to infinity (AUCinf), time to 
maximum observed concentration (tmax), terminal half-life (t1/2), clearance (CL), and volume of 
distribution (Vz) as appropriate 
x 
Immunogenic responses to BGB-DXP593 evaluated through the detection of antidrug 
antibodies (ADAs) 
Exploratory: 
Study Design 
This is a Phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety and 
efficacy of BGB-DXP593 in patients with mild to moderate COVID-19. 
After providing written informed consent, completing all screening assessments, and being confirmed 
as eligible for study participation, patients will be randomized in a 1:1:1:1 ratio to receive placebo, 
BGB-DXP593 5 mg/kg, BGB-DXP593 15 mg/kg, or BGB-DXP593 30 mg/kg. Patient randomization 
will be stratified by country and disease severity (mild versus moderate COVID-19). The patients will 
receive a single intravenous infusion of placebo or BGB-DXP593 over 30 to 90 minutes. The patients 
will then be followed to Day 113 (± 7 days) to assess the efficacy, safety, PK, and immunogenicity. 
Nasopharyngeal swabs will be collected according to the Schedule of Assessments to evaluate the 
change in viral load using RT-qPCR testing of SARS-CoV-2. 
An Independent Data Monitoring Committee (IDMC) will periodically monitor safety and efficacy 
data. The first safety review is planned after at least 12 patients have received study treatment and have 
been followed up for 7 days. 
The study design schema is in Section 3, Figure 2. 
Study Assessments: 
Patients will be monitored for safety, efficacy, PK, and immunogenicity during the study. 
Assessments of safety will include adverse events, SAEs, clinical laboratory tests, physical 
examinations, vital signs, and electrocardiograms (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. 
PK, ADA and biomarker sampling will be collected at specific intervals from Day 1 to Day 113. 
RT-qPCR analysis will be used to assess the SARS-CoV-2 viral load in different samples at various 
timepoints, including nasopharyngeal swabs, saliva, and blood.  
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World Health Organization (WHO) 8-point ordinal scale will be used for clinical status assessment. 
Key Eligibility Criteria: 
To participate in this study, patients must have laboratory-confirmed SARS-CoV-2 infection (positive 
reverse transcription-polymerase chain reaction [RT-PCR] test or other testing methods authorized by 
local regulatory authorities) in any samples following local practice  72 hours prior to screening; 
have experienced COVID-19 symptoms for  7 days prior to treatment assignment (such as fever, 
cough, shortness of breath, sore throat, diarrhea, vomiting, and dysgeusia); and agree to the collection 
of nasopharyngeal swabs, saliva, and venous blood. Patients should not have oxygen saturation (SpO2) 
 % on room air or ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to 
fractional inspired oxygen (FiO2   UHVSLUDWRU\ UDWH  PLQ or KHDUW UDWH  PLQ 3DWLHQWV
should have no history of a positive SARS-CoV-2 serology test; no prior investigational intervention 
for SARS-CoV-2 prophylaxis within 30 days before dosing; and no prior treatment with a 
SARS-CoV-2 specific monoclonal antibody or convalescent COVID-19 plasma; and should not have 
participated in a previous SARS-CoV-2 vaccine study. 
Investigational Product, Dose, and Mode of Administration: 
BGB-DXP593 will be administered intravenously at a dose of 5 mg/kg, 15 mg/kg or 30 mg/kg for 30 
to 90 minutes; placebo will be administered intravenously for 30 to 90 minutes. 
Statistical Methods: 
Analysis Sets 
The Intent-to-Treat (ITT) Analysis Set includes all randomized patients. Patients will be analyzed 
according to the treatment assigned at randomization. This will be the primary analysis set for efficacy 
analyses. 
The Safety Analysis Set includes all patients who have received the study drug (BGB-DXP593 or 
placebo). Patients will be analyzed according to their actual treatment received. The Safety Analysis 
Set will be used for all safety analyses. 
The PK Analysis Set includes all patients who have received the study drug (BGB-DXP593) per the 
protocol and for whom any postdose PK data are available. 
The ADA Analysis Set includes all the patients who have received the study drug and in whom both 
baseline ADA and at least 1 postbaseline ADA results are available. 
Primary Efficacy Analysis 
The statistical hypotheses to be tested for the primary endpoint are as follows:  
H0: there is a flat dose response curve comparing change from baseline to Day 8 in SARS-CoV-2 viral 
shedding in the placebo and the BGB-DXP593 dose groups 
H1: there is a non-flat dose response curve indicating a benefit of BGB-DXP593 over placebo 
The primary analysis uses methodology for dose finding, employing both multiple comparison 
procedures and modelling techniques (MCPMod). The MCPMod procedure allows for simultaneous 
evaluation of different potential dose response patterns, whilst protecting the overall probability of 
Type I error (one-VLGHG Į RI  
Safety Analyses 
Safety will be assessed by monitoring and recording all adverse events, laboratory values, vital signs, 
and physical examinations. Descriptive statistics will be used to analyze all safety data by actual 
treatment arm in the Safety Analysis Set. 
Pharmacokinetic Analyses 
Noncompartmental or model-based analysis will be carried out for BGB-DXP593 serum 
concentrations. Parameters, such as Cmax, tmax, t1/2, AUCt, AUCinf, AUC0-29, CL, and Vz (as appropriate 
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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 patients who develop detectable ADAs. The incidence of positive and neutralizing ADAs 
will be reported for evaluable patients. The effect of immunogenicity on PK and safety may be 
evaluated if data allow. 
Sample Size Calculation 
Forty-one patients are needed with primary endpoint data per arm to provide at least 82% power to 
detect non-flat dose-response relationship at one-VLGHG VLJQLILFDQFH OHYHO Į   0&30RG DSSURDFK
is used. In order to ensure 41 patients per arm with primary endpoint data, at least 43 patients per arm 
need to be randomized. 
The calculation has been performed using R software, version 3.6.1. 
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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 
AUCinf 
AUC from time zero to infinity 
AUCt 
AUC from time zero to the time of the last quantifiable concentration 
AUC0-29 
AUC from time zero to Day 29 
CI 
confidence interval 
CL 
clearance 
Cmax 
maximum observed concentration 
COVID-19 
coronavirus disease 2019 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture (system) 
GCP 
Good Clinical Practice 
IC50 
concentration for inhibition of 50% maximal activity 
IC99 
concentration for inhibition of 99% maximal activity 
ICF 
informed consent form 
IDMC 
Independent Data Monitoring Committee  
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
mAb 
monoclonal antibody 
MCPMod 
multiple comparison procedures and modelling approaches 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI-CTCAE 
National Cancer Institute-Common Terminology Criteria for Adverse Events 
PK 
pharmacokinetic(s) 
RBD 
receptor binding domain 
RT-PCR 
reverse transcription-polymerase chain reaction 
RT-qPCR 
reverse transcription-quantitative polymerase chain reaction 
SAE 
serious adverse event 
SARS-CoV-2 
Severe Acute Respiratory Syndrome Coronavirus 2 
TEAE 
treatment-emergent adverse event 
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Abbreviation 
Definition 
tmax 
time to maximum observed concentration 
t1/2 
terminal half-life 
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 et al 
2020). As of July 2020, over 14 million confirmed cases of COVID-19 worldwide have been 
reported to World Health Organization (WHO). COVID-19 is threatening the global public 
health, and the ongoing spread of COVID-19 has resulted in a worldwide pandemic demanding 
effective interventions against SARS-CoV-2 infections.  
Currently, several treatment strategies are used clinically or are under development, such as 
viral-targeting therapeutics and host-targeting agents (such as anti-interleukin-6 antibodies, 
glucocorticoids) for the treatment of COVID-19. Unfortunately, there is no vaccine or 
prescribing drug regimen which has demonstrated significant efficacy in the treatment of 
COVID-19 patients in clinical studies so far (Jean et al 2020). 
Convalescent plasma therapy has been used to treat COVID-19 by providing passive immune 
responses to viral infection. However, the outcomes of passive plasma therapy are unpredictable 
due to the variability of sera from different patients (Zhou and Zhao 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 and Roback 2020). 
Neutralizing monoclonal antibodies (mAbs) generated from plasma of convalescent patients 
provide more specific and consistent immune response. The antibodies with high affinity to the 
virus can be selected. Although several SARS-CoV-2-specific neutralizing mAbs are under 
clinical investigation, no clinical studies have been completed to date. Therefore, neutralizing 
antibodies that effectively block virus entry into host cells are urgently needed (Cao et al 2020). 
BGB-DXP593 (also named DXP593, BD-368-2, and WBP2281) is a highly potent neutralizing 
immunoglobulin G (IgG)1 monoclonal antibody specifically against SARS-CoV-2. 
1.2. 
BGB-DXP593 as a SARS-CoV-2 Neutralizing Monoclonal Antibody 
SARS-CoV-2 infects host cells through binding to human angiotensin-converting enzyme 2 
(ACE2) expressed on host cells by the receptor-binding domain (RBD) of its Spike (S) protein 
(Walls et al 2020). BGB-DXP593 binds to the S protein RBD of SARS-CoV-2 with high 
specificity and affinity, efficiently blocking the binding of RBD to ACE2, thus preventing virus 
from entering host cells. 
1.2.1. 
Nonclinical 
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@   Q0 %*%-DXP593 efficiently blocks the 
binding of RBD to its receptor ACE2 with a concentration for inhibition of 50% maximal 
activity (IC50) of 0.81 nM in a competition enzyme-linked immunosorbent assay (ELISA). 
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The crystal structure of BGB-DXP593 antigen-binding fragment (Fab) in complex with RBD 
suggests that BGB-DXP593 would interfere with the interaction between RBD and ACE2. The 
structure shows that
 of 
RBD have direct contact with BGB-DXP593. In addition, the structure also suggests that 
BGB-DXP593 would clash with both protomers in the ACE2 dimer.  
In cell-based assays, BGB-DXP593 inhibits SARS-CoV-2 infections in both pseudovirus and 
authentic virus systems with an IC50 of 8 pM (0.0012 g/mL) and 0.1 nM (0.015 g/mL), 
respectively, and a concentration for inhibition of 99% maximal activity (IC99) of 0.6 nM 
(0.09 g/mL) and 1.08 nM (0.162 g/mL). BGB-DXP593 has wild-type human IgG1 fragment 
crystallizable region (Fc), which exhibit similar binding profile as regular IgG1 antibody in terms 
of binding to Fc Ȗ UHFHSWRUV )FȖ5V) 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 post-exposure 
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, achieving undetectable viral levels in the prophylactic treatment 
model, where BGB-DXP593 was injected 24 hours before the virus infection. Consistent with 
this observation, the body weights of the treated mice remained in stasis while that of the control 
mice dropped by over 5% at 5 days post infection. Similarly, BGB-DXP593 reduced the virus 
load by over 1000 fold in the post-exposure prophylaxis treatment model, where antibody was 
injected 2 hours after the infection. Additionally, the body weight of the treated mice remained 
unchanged over a course of 5 days, comparable to those in the prophylactic treatment model, 
suggesting that BGB-DXP593 maintained the fitness of the infected mice. 
In the hamster post-exposure prophylaxis treatment model, BGB-DXP593 injection at a dose 
level of 2, 5, 10, or 20 mg/kg led to dose-dependent lung viral reduction at 7 days post infection, 
with the best response observed within the highest tested dose group (ie, 20 mg/kg). All dose 
groups showed improvement in body weight loss compared with the control group. 
BGB-DXP593 (20 mg/kg) also demonstrated a preventive effect in hamster model when injected 
1 day or 3 days before infection, while the more contemporaneous 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. 
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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. A tissue cross reactivity was evaluated in the normal frozen tissues from 
both monkeys and humans. Cytokine release responses were 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 study. Based on the available data, the missing information is not considered 
to have an impact on the results and data interpretation.  
In the 14-day repeat-dose study in monkeys at the doses up to 300 mg/kg, no mortality or 
morbidity was noted throughout the study; no treatment-related findings or changes were noted, 
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 cardiovascular, respiratory, or central 
nervous systems functions were noted. The systemic exposure 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 marked drug accumulation or changes were noted after weekly repeated doses. 
The NOAEL (No Observed Adverse Effect Level) is considered as 300 mg/kg in this study 
based on available data, which is approximately 60-fold of the proposed first-in-patient dose 
(5 mg/kg) and 10-fold of the proposed highest human dose (30 mg/kg) based on body weight. 
No specific binding of BGB-DXP593 was detected in either normal monkey or human tissues in 
the tissue cross reactivity study by 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. 
Clinical Experience 
A first-in-human study of BGB-DXP593 in healthy subjects (Study BGB-DXP593-101) is 
ongoing. No serious adverse event has been reported to date. 
1.3. 
Study Rationale 
COVID-19 is an acute respiratory syndrome caused by SARS-CoV-2 infection. BGB-DXP593 is 
a neutralizing mAb against the SARS-CoV-2 selected from convalescent COVID-19 patients. By 
binding to the RBD on the S protein of the virus, BGB-DXP593 can prevent the virus from 
entering the cells. Its pre- and post-exposure prophylaxis effects in hACE mice have been 
demonstrated (Cao et al 2020). 
A few studies suggested that high viral load is associated with increased mortality (Fajnzylber et 
al 2020; Pujadas et al 2020; Wolfel et al 2020). Amongst the participants hospitalized with 
COVID-19, higher prevalence of detectable SARS-CoV-2 plasma viral load was associated with 
worse respiratory disease severity, lower absolute lymphocyte counts, and increased markers of 
inflammation, including C-reactive protein and interleukin-6 (Fajnzylber et al 2020). This study 
will explore if BGB-DXP593 can effectively reduce viral load in collected samples.  
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Patients who have experienced COVID-19 symptoms less than 7 days will be enrolled. By 
7 days after onset of symptoms, anti-SARS-CoV-2 immunoglobulin M (IgM) or IgG can be 
detected in around 50% of patients (Wolfel et al 2020). Presence of anti-SARS-CoV-2 IgG in 
patients’ blood is associated with reduced viral load. High viral loads were rare in individuals 
who had seroconverted (Bryan et al 2020).  
This study will assess efficacy of BGB-DXP593 in lowering viral load at different dose levels. 
To date, there is no drug approved or recommended for mild to moderate COVID-19 (NIH 
COVID-19 treatment guidelines, 2020). Hence, using placebo as the control is appropriate.  
To assess viral load at different time points, nasopharyngeal swabs, saliva and blood samples 
will be collected. Nasopharyngeal swabs are the clinically recommended sampling method for 
virologic tests. In addition, the viral load change in saliva samples will be assessed. The viral 
load in nasopharyngeal samples will be used for primary efficacy analysis. Collection of saliva is 
non-invasive. Studies suggested that viral loads in saliva are comparable to those in 
nasopharyngeal swabs during the first week of symptoms and decrease over time. Saliva can be 
positive up to 20 days post-symptom onset with viral loads correlating with symptom severity 
and degree of tissue damage. The viral load in saliva has good association with nasopharyngeal 
swabs (Khurshid et al 2020). A majority of patients do not have viremia. However, detection of 
viral RNA in blood is associated with poor outcomes. 
1.3.1. 
Rationale for Selection of BGB-DXP593 Doses  
A single dose of BGB-DXP593 of 5 mg/kg, 15 mg/kg and 30 mg/kg, as the dose levels being 
tested, are proposed based on an overall assessment of in vitro activity of BGB-DXP593 and 
toxicology data as describe below. 
Based on the toxicology evaluation in cynomolgus monkeys, the NOAEL was determined to be 
300 mg/kg. Applying a safety factor of 10, the MRSD (maximum recommended starting dose) is 
estimated as 30 mg/kg (body weight-based) which is the highest dose being tested in this study. 
In addition, based on the AUC from time zero to infinity (AUCinf) and Cmax after the second dose 
at 300 mg/kg NOAEL in the toxicity study in monkeys, the projected safety margins at the 
proposed highest dose of 30 mg/kg are 5.0 and 11.1, respectively, which reflects favorably on the 
safety profile of BGB-DXP593 (Table 1). 
The two lower doses of 5 mg/kg and 15 mg/kg are based on the results of the in vitro virus 
neutralization assays. In the in vitro virus neutralization assays, BGB-DXP593 potently inhibited 
SARS-CoV-2 infections in both pseudovirus and authentic virus systems with an IC99 of 
0.09 g/mL and 0.162 g/mL, respectively. Predicted serum and lung concentrations at various 
dose levels were compared to the IC99 of 0.162 g/mL from the authentic virus neutralization 
assay (higher value from the two assays). The biodistribution of monoclonal antibodies in lungs 
was taken into consideration. It has been reported in literature that lung biodistribution ranges 
from 0.5% to 15% (Hart et al 2001; Shah and Betts 2013; Hershberger et al 2019; Eigenmann et 
al 2017), therefore, a conservative value of 1% lung biodistribution was chosen for the 
simulations.  
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Predicted human serum concentration-time profiles showed that BGB-DXP593 doses at and 
above 5 mg/kg would maintain lung concentrations above the IC99 of 0.162 g/mL over 29 days
(Figure 1). However, given that the impact of SARS-CoV-2 on lung biodistribution of 
monoclonal antibodies is not known, the two higher dose levels of 15 mg/kg and 30 mg/kg will 
also be tested. 
Please refer to the BGB-DXP593 Investigator’s Brochure for more detailed information. 
Figure 1: 
Simulated BGB-DXP593 Serum and 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. 
Solid lines: projected serum concentrations; dashed lines: projected lung concentrations assuming 1% 
biodistribution. 
Table 1: 
Projected Safety Margins at Proposed Doses in Humans 
Safety margin 
BGB-DXP593 Dose (mg/kg) 
5 
15 
30 
AUC based 
30.3 
10.1 
5.0 
Cmax based 
66.4 
22.1 
11.1 
Abbreviations: AUC, area under the concentration-time curve; Cmax, maximum observed concentration 
1.3.2. 
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, AUC from time zero to the time of the last quantifiable concentration (AUCt), 
AUC from time zero to Day 29 (AUC0-29), AUCinf, time to maximum observed concentration 
(tmax), terminal half-life (t1/2), clearance (CL), and volume of distribution (Vz). 
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Rich PK sampling will be performed in the first-in-human study in healthy subjects (Study 
BGB-DXP593-101). PK sampling in this study is limited to essential site visits to reduce patient 
burden. 
1.3.3. 
Rationale for Biomarker Strategy 
Biomarker analyses will be performed to evaluate study treatment effects induced in patients as 
well as to explore potential predictive biomarkers of response to BGB-DXP593. 
Seroconversion for patients with COVID-19 usually happens within the first week after symptom 
onset (Wolfel et al 2020). It has been shown that seroconversion occurred after 7 days in 50% of 
patients and almost all COVID-19 patients had neutralizing antibodies within 1 month after 
symptom onset, thus the existing anti-SARS-CoV-2 antibodies in patients may have an impact 
on the efficacy of BGB-DXP593, which is also an neutralizing antibody for SARS-CoV-2. 
Therefore, the baseline SARS-CoV-2 serology antibody levels may be related to the treatment 
effects of BGB-DXP593. Recent studies have suggested that the certain mutations on 
SARS-CoV-2 virus may impact the infectivity and severity of the virus, especially the mutations 
on the receptor binding domain of SARS-CoV-2, which may also impact the neutralizing 
activities of SARS-CoV-2 neutralizing antibodies (Baum et al 2020; Korber et al 2020; Li et al 
2020). Thus, certain mutations on SARS-CoV-2 genome may also be related to the treatment 
effects of BGB-DXP593.  
In addition, patients with COVID-19 have shown a strong upregulation of cytokine and 
interferon production, it is believed that dysregulated host immune response and production of 
inflammatory cytokines, known as the “cytokine storm”, correlates with disease severity and 
poor prognosis of SARS-CoV-2 infection (Tay et al 2020). Therefore, serum cytokine levels 
could be a marker for evaluating disease severity and the treatment effects of anti-SARS-CoV-2 
neutralizing antibodies. 
Considering the immune response induced by SARS-CoV-2 infection varies a lot among 
different patients, all patients may not be equally likely to benefit from treatment with 
anti-SARS-CoV-2 neutralizing antibodies. Predictive biomarker samples collected before dosing 
will be assessed in an effort to identify those patients with certain gene signatures who are most 
likely to respond to BGB-DXP593. Thus, gene signatures at baseline and after treatment in 
peripheral blood may serve as predictive biomarkers and may also help to explore the 
mechanism of response. 
1.4. 
Benefit-Risk Assessment 
On March 11, 2020, the Novel Coronavirus Disease, COVID-19, was declared a pandemic by 
the WHO. As of July 9, 2020, more than 12 million cases of COVID-19 have been reported 
globally, including more than 550,000 deaths. However, only remdesivir is approved for the 
treatment of severe COVID-19, and thus the unmet medical needs remain high. 
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Several studies showed that high viral load is associated with increased mortality. 
Seroconversion (detection of anti-SARS-CoV-2 IgM or IgG in blood) occurred in around 50% of 
patients 7 days after disease onset. Presence of anti-SARS-CoV-2 IgG is associated with viral 
load reduction (Bryan et al 2020; Fajnzylber et al 2020; Pujadas et al 2020; Wolfel et al 2020). 
With early administration of antiviral neutralizing antibodies, patients may benefit from early 
and rapid reduction of viral load and potential improved clinical outcomes. 
BGB-DXP593 is a potent neutralizing antibody to SARS-CoV-2. It is human IgG type 1 selected 
from blood of convalescent patients. In preclinical studies, its pre- and post-exposure 
prophylactic effects to COVID-19 have been demonstrated. In a toxicological study in monkeys, 
no adverse events (AEs) were observed with repeated doses of BGB-DXP593 30-300 mg/kg.  
As an exogeneous protein, use of BGB-DXP593 might be related with hypersensitivity reactions, 
though the immunogenicity is considered low due to its human origin. Potential 
antibody-dependent enhancement (ADE) has been observed in some viral infections, such as 
Dengue fever. Possibility of ADE with passive immunity cannot be excluded in COVID-19. 
However, clinical experiences with RSV, influenza and dengue provide strong evidence that the 
circumstances that are proposed to lead to ADE of disease—including low affinity or 
cross-reactive antibodies with limited or no neutralizing activity or suboptimal titres—are very 
rarely implicated as the cause of severe viral infection in the human host (Arvin et al 2020). 
BGB-DXP593 is a highly potent neutralizing antibody, and thus is unlikely to cause ADE. In 
addition, a large number of COVID-19 patients have received convalescent plasma therapy, 
where no hints of ADE have been identified (Joyner et al 2020).  
There are no FDA-approved treatments or accepted standardized medical treatment options 
indicated for mild to moderate COVID-19. Patients may benefit from the treatment of 
BGB-DXP593 based on its mechanism of action and the proven efficacy in COVID-19 animal 
models. BGB-DXP593 has a favorable preclinical safety profile. Patients enrolled in this clinical 
study will be closely monitored by means of reporting AEs, recording vital signs, and conducting 
clinical laboratory safety tests of blood and urine. The favorable preclinical safety profile, 
potential wide range application in the COVID-19 population and high unmet medical need 
provides substantive evidence that BGB-DXP593 has a favorable risk-benefit profile.  
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 ENDPOINTS 
2.1. 
Study Objectives 
2.1.1. 
Primary Objective 
x To evaluate the efficacy of BGB-DXP593 administered intravenously as a single dose in 
patients with mild to moderate COVID-19 
2.1.2. 
Secondary Objectives 
x To evaluate the safety of BGB-DXP593 administered intravenously as a single dose in 
patients with mild to moderate COVID-19 
x To characterize the pharmacokinetic (PK) profile of BGB-DXP593 administered 
intravenously as a single dose in patients with mild to moderate COVID-19 
x To evaluate the potential immunogenicity of BGB-DXP593 administered intravenously 
as a single dose in patients with mild to moderate COVID-19 
2.1.3. 
Exploratory Objective 
x 
2.2. 
Study Endpoints 
2.2.1. 
Primary Endpoint 
x Change from baseline to Day 8 in Severe Acute Respiratory Syndrome Coronavirus 2 
(SARS-CoV-2) viral shedding as measured by reverse transcription-quantitative 
polymerase chain reaction (RT-qPCR) in nasopharyngeal swab samples 
2.2.2. 
Secondary Endpoints 
x Time-weighted average change in SARS-CoV-2 viral shedding as measured by RT-qPCR 
in nasopharyngeal swab samples from baseline to Day 15 
x Change in SARS-CoV-2 viral shedding as measured by RT-qPCR in nasopharyngeal 
swab samples from baseline to Day 15 
x Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR 
in any tested samples 
x Proportion of patients requiring hospitalization due to worsened COVID-19 
x Time to resolution of all COVID-19-related symptoms 
x All-cause mortality rate at Day 29 
x Incidence and severity of treatment-emergent adverse events (TEAEs) and serious 
adverse events (SAEs) 
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x PK parameters: 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 Day 29 (AUC0-29), AUC from time zero to 
infinity (AUCinf), time to maximum observed concentration (tmax), terminal half-life (t1/2), 
clearance (CL), and volume of distribution (Vz) as appropriate 
x Immunogenic responses to BGB-DXP593 evaluated through the detection of antidrug 
antibodies (ADAs) 
2.2.3. 
Exploratory Endpoints 
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3. 
STUDY DESIGN 
3.1. 
Summary of Study Design 
This is a Phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy 
and safety of BGB-DXP593 in patients with mild to moderate COVID-19. 
The study will be conducted across approximately 20 to 30 sites internationally. 
After providing written informed consent, completing all screening assessments, and being 
confirmed as eligible for study participation, patients will be randomized in a 1:1:1:1 ratio to 
receive placebo, BGB-DXP593 5 mg/kg, BGB-DXP593 15 mg/kg, or BGB-DXP593 30 mg/kg. 
Patient randomization will be stratified by country and disease severity (mild versus moderate 
COVID-19). The patients will receive a single intravenous infusion of placebo or BGB-DXP593 
over 30 to 90 minutes. The patients will then be followed to Day 113 (± 7 days) to assess the 
efficacy, safety, PK, and immunogenicity. Nasopharyngeal swabs will be collected according to 
the Schedule of Assessments (Appendix 1) for RT-qPCR testing of SARS-CoV-2 to assess the 
change in viral load after study treatment. Approximately 172 patients will be randomized. 
An Independent Data Monitoring Committee (IDMC) will periodically monitor safety and 
efficacy data. The first safety review is planned after at least 12 patients have been treated and 
followed up for 7 days. 
The study schema is provided in Figure 2. 
Figure 2: 
Study Schema 
 
NRte: Patients will be randomized based on stratification factors of country and disease severity (mild versus 
moderate COVID-19).  
Patients will be monitored for safety, efficacy, PK, and immunogenicity during the study. 
Assessments of safety will include AEs, SAEs, clinical laboratory tests, physical examinations, 
vital signs, and electrocardiograms (ECGs). AEs will be graded for severity according to 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. 
RT-qPCR analysis will be used to assess the SARS-CoV-2 viral load in different samples at 
various timepoints, including nasopharyngeal swabs, saliva, and blood. The viral load in 
nasopharyngeal swabs will be used for primary efficacy analysis.  
WHO 8-point ordinal scale will be used for clinical status assessment. 
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PK and ADA sampling will be conducted at timepoints specified in Appendix 2. 
Biomarker analysis will include, but are not limited to, SARS-CoV-2 mutations, serology, 
cytokines, and gene expression signatures. 
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. 
 
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4. 
STUDY POPULATION 
The specific eligibility criteria for selection of patients are provided in Section 4.1 and 
Section 4.2. The sponsor will not grant any eligibility waivers. 
4.1. 
Inclusion Criteria 
Each patient must meet all of the following inclusion criteria to be considered eligible for 
participation in this study: 
1. Participant must be at least 18 years of age at the time of signing the informed consent.  
2. Laboratory-confirmed SARS-CoV-2 infection (positive  reverse transcription-polymerase 
chain reaction [RT-PCR] test or other testing methods authorized by local regulatory 
authorities) in any samples following local practice  72 hours prior to screening 
3. Have experienced COVID-19 symptoms for  7 days prior to treatment assignment, such 
as fever, cough, shortness of breath, sore throat, diarrhea, vomiting, and dysgeusia 
4. Agree to the collection of nasopharyngeal swabs, saliva, and venous blood 
5. Female patients of childbearing potential must be willing to use a highly effective method 
of birth control (see Appendix 4) from the time of study enrollment until 4 months after 
the study dosing 
6. Male patients with female partners of childbearing potential must be willing to use a 
highly effective method of birth control (see Appendix 4) from the time of study 
enrollment until 4 months after the study dosing 
7. 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 
Patients who meet any of the following criteria will be excluded from this study: 
Medical Histories or Conditions 
1. Patient with severe COVID-19 having oxygen saturation (SpO2   RQ URRP DLU RU
ratio of arterial oxygen partial pressure (PaO2 in millimeters of mercury) to fractional 
inspired oxygen (FiO2) <  UHVSLUDWRU\ UDWH  PLQ or heart UDWH  125/min 
Note: For high altitude areas, PaO2/FiO2 ratio should be adjusted using formula: 
PaO2/[FiO2×(barometric pressure/760)] 
2. Patient requires mechanical ventilation or anticipated impending need for mechanical 
ventilation 
3. Known allergies to any of the components used in the formulation of the interventions 
4. Hemodynamic instability requiring use of pressors within 24 hours prior to treatment 
assignment 
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5. Suspected or proven serious, active bacterial, fungal, viral, or other infection (besides 
COVID-19) that in the opinion of the investigator could constitute a risk when taking 
intervention 
6. Any comorbidity requiring surgery within 7 days prior to screening, or that is considered 
life-threatening within 29 days prior to screening  
7. Any serious concomitant systemic disease, condition, or disorder that, in the opinion of 
the investigator, should preclude participation in this study 
8. History of a positive SARS-CoV-2 serology test (anti-SARS-CoV-2 IgA, IgM, or IgG) 
9. History of a positive SARS-CoV-2 test (RT-PCR or other testing authorized by local 
regulatory authorities) prior to the one serving as eligibility for this study 
10. Pregnant or breast feeding 
11. Any concurrent immune-compromising conditions, including a) a known history of 
immunodeficiency disorders; b) malignant or nonmalignant disorders requiring use of 
immunosuppressive therapies 
12. Any history of a severe allergic reaction prior to enrollment that has a reasonable risk of 
recurrence during the study 
Prior/Concomitant Therapy 
13. Have received an investigational intervention for SARS-CoV-2 prophylaxis within 
30 days before dosing 
14. Have received treatment with a SARS-CoV-2 specific monoclonal antibody  
15. History of convalescent COVID-19 plasma treatment 
16. Have received remdesivir 
17. Have received any investigational treatment for COVID-19, including but not limited to 
antiviral agents, corticosteroids, interleukin-1 inhibitors, interleukin-6 inhibitors and 
intravenous immunoglobulin within 30 days before dosing 
Prior/Concurrent Clinical Study Experience 
18. Participation in a previous SARS-CoV-2 vaccine study 
19. Participation, within the last 30 days, in a clinical study involving an investigational 
intervention. If the previous investigational intervention has a long half-life, 5 half-lives 
or 30 days, whichever is longer, should have passed. 
20. Concurrently enrolled in any other type of medical research judged not to be 
scientifically or medically compatible with this study 
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Diagnostic Assessments 
21. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3 x upper limit of 
normal (ULN), and/or bilirubin > 2 x ULN 
22. Liver insufficiency classified as Child-Pugh Grade C  
23. Renal insufficiency: estimated glomerular filtration rate (eGFR) < 30 mL/min using 
Cockcroft and Gault formula 
24. Patients who have been hospitalized due to COVID-19 
For COVID-19 patients that have been hospitalized regardless of disease severity due to 
local or country regulations, eligibility should be confirmed with the sponsor or designee.  
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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. One or multiple 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 is 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 
FRQGLWLRQV WKDW DUH FRQVLVWHQW ZLWK VWXG\ GUXJဩVSHFLILF UHTXLUHPHQWV %*%ဩ';3 PXVW EH
stored at temperatures between 2°C and 8°C 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 is a sterile concentrate solution for dilution for infusion. It shares the same formulation 
as BGB-DXP593 without the active pharmaceutical ingredient (BGB-DXP593 antibody). Each 
placebo vial is packaged into a single-carton box. The contents of the label for placebo vials will 
be in accordance with all applicable local regulatory requirements. 
The study drug must be kept at the temperature condition as specified on the label. 
Refer to the Pharmacy Manual for details regarding intravenous administration, accountability, 
and disposal. 
5.2. 
Dosage, Administration, and Compliance 
BGB-DXP593 or placebo are administered intravenously with a single dose. On the day of 
dosing, study drug (BGB-DXP593 or placebo) should be reconstituted with 0.9% sodium 
chloride and will be administered by intravenous infusion for 30 to 90 minutes. Specific 
instructions for BGB-DXP593 preparation and administration are provided in the Pharmacy 
Manual. The dose of BGB-DXP593 for each patient will be based on the patient’s actual body 
weight on the day of drug administration. 
As a routine precaution, patients 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. 
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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 by an unblinded pharmacist. Refer to the Pharmacy 
Manual for details of study drug management, drug preparation, storage, and administration. 
Guidelines for infusion-related reactions are provided in detail in Section 9.7. 
5.3. 
Incorrect Administration 
Any incorrect administration of the study drug should be noted in the patient’s chart and on the 
appropriate electronic case report form (eCRF) without the study drug kit number. AEs 
associated with 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 measures 
should be administered as appropriate. 
5.4. 
Dose Interruption or Modification 
There will be no dose reduction of study drug in this study. A dose interruption is an interruption 
of an infusion. 
Each patient will receive a single dose of the study drug via intravenous infusion. The infusion 
may be temporarily interrupted due to infusion-related reactions or other medical events. 
If the AE is resolved or recovered to Grade 1 (whichever is more severe), the infusion should be 
resumed within 2 hours of the infusion interruption. If the patient is unable to resume the study 
drug within 2 hours of the infusion interruption, then the patient should be discontinued from the 
study treatment. 
The treatment modification for infusion-related reactions is provided in Section 9.7.1. 
5.5. 
Blinding 
In this study, patients will be randomized to receive BGB-DXP593 or matched placebo in a 
double-blind fashion. The single dose of study drug will be prepared by an unblinded pharmacist. 
At the study sites, only the unblinded pharmacist for study drug preparation will know the 
treatment allocation of patients; other members who are directly involved in the clinical conduct 
of the study, including the staff for study drug administration, will not know. Both the 
intravenous infusion of BGB-DXP593 and placebo will be colorless. All the follow-up 
evaluations will be performed by blinded study site staff. It is imperative to maintain the blind to 
patient treatment assignment such that neither the investigator, nor the patient, nor medical or 
ancillary medical staff (except for the unblinded pharmacist who is responsible for the 
preparation of the study drug and has access to dispensation records), nor the blinded sponsor 
staff or its designees will know which study drug is being administered. Due to the ongoing need 
to assess safety, a limited number of sponsor staff will not be blinded to patient treatment 
assignment (see Section 11.1). 
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Every effort should be made to avoid unblinding the patient’s treatment assignment unless 
necessary. Unblinding may be indicated and permissible only in specific situations as described 
below and if necessary, for the patient’s welfare. Unblinding would occur through Interactive 
Response Technology (IRT) as per the instructions in the IRT site user manual. If unblinding has 
occurred, the sponsor must be notified immediately using the Unblinding Event Form. To ensure 
the continued blinding of study personnel, this form will not include the treatment assignment.  
Patients will remain on study for study follow-up. 
The study will be unblinded after primary analysis database lock. 
5.5.1. 
Emergency Unblinding 
In case of an emergency, such as when a patient has an AE suspected to be related to the 
investigational drug product and for which management of the AE with one or more drug 
products with substantial toxicity or invasive procedures is being considered, unblinding can 
occur. The investigator has the sole responsibility for determining if unblinding of a patient’s 
treatment assignment is warranted. Patient safety must always be the first consideration in 
making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to inform the medical monitor of their intent before 
unblinding a patient’s treatment assignment unless this could delay emergency treatment of the 
patient. If a patient’s treatment assignment is unblinded, the sponsor must be notified 
immediately. 
The investigator performs the emergency unblinding for AEs through an IRT System. 
5.5.2. 
Inadvertent Unblinding 
Every effort will be made to blind both the patient and the investigator to the identity of the 
treatment assignment (ie, BGB-DXP593 or placebo), but the inadvertent unblinding of a patient 
may occur. If an investigator, site personnel performing assessments, or patient is unblinded, the 
unblinding will not be sufficient cause (in and of itself) for that patient to be discontinued from 
study or excluded from any analyses. 
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6. 
PRIOR AND CONCOMITANT THERAPY 
6.1. 
Permitted Concomitant Medications/Procedures 
Unless noted otherwise, most concomitant medications and therapies deemed necessary and in 
keeping with local standards of medical care at the discretion of the investigator for a patient’s 
welfare are allowed. Standard of care therapy for mild to moderate COVID-19 is allowed 
according to local treatment guidelines.  
All concomitant medications, including all prescription and over-the-counter drugs, supplements, 
and intravenous medications and fluids, taken by or administered to the patient within 30 days 
before the study drug administration and during the study will be recorded in the eCRF including 
indication and dates of administration. 
6.2. 
Prohibited Concomitant Medications/Procedures 
Any approved or investigational drugs with established or potential activity against 
SARS-CoV-2 within 30 days of study drug administration are prohibited, including but not 
limited to, remdesivir, other antiviral agents, corticosteroids, interleukin-1 inhibitors, 
interleukin-6 inhibitors, and immunoglobulin. If clinically indicated, patients with worsened 
COVID-19 may be treated with standard of care therapy according to local treatment guidelines. 
For example, dexamethasone is allowed in hospitalized patients requiring oxygen support. 
6.3. 
Potential Interactions Between the Study Drug 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 evaluations will be performed within 3 days before the study drug administration. A 
patient 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. Rescreening is not allowed. If the site is able to complete all the 
screening procedures, randomization, and study treatment in 1 day, the screening assessments 
can be combined with the Day 1 assessments. 
7.1.1. 
Informed Consent and Screening Log 
Voluntary, written informed consent for participation in the study must be obtained before 
performing any study-specific procedures. ICFs for enrolled patients and for patients who are 
screened but not enrolled will be maintained at the study site.  
The investigator will maintain a screening log to record details of all patients screened and to 
confirm eligibility or record reasons for screening failure, as applicable. 
7.1.2. 
Patient Numbering 
After obtaining informed consent, study site personnel will access the IRT system to assign a 
unique patient number to a potential study participant. Once a patient number has been assigned 
to a patient, it cannot be reassigned to any other patient. 
7.2. 
Enrollment 
7.2.1. 
Confirmation of Eligibility 
All screening results and relevant medical history must be available before eligibility can be 
determined. The investigator must confirm that all eligibility criteria are met. All inclusion 
criteria must be met and none of the exclusion criteria may apply. No eligibility waivers will be 
granted. 
7.2.2. 
Enrollment/Randomization 
Site personnel will randomize the patients to treatment arms (placebo, BGB-DXP593 5 mg/kg, 
BGB-DXP593 15 mg/kg, or BGB-DXP593 30 mg/kg) based on stratification factors of country 
and disease severity (mild versus moderate COVID-19), then the unblinded pharmacist will 
access the IRT system and dispense the study drug. 
7.3. 
Treatment 
Patients randomized will be treated with the study drug on Day 1 as described in Section 5.2. A 
single dose of the study drug will be administered intravenously to the patient. Vital signs of the 
patients will be monitored approximately every 15 minutes during the infusion and then hourly 
till 2 hours after the infusion. See Appendix 1 for detailed procedures on Day 1. 
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Refer to Section 7.5 for additional considerations regarding treatment continuation and 
withdrawal. 
7.4. 
Follow-up Period 
The follow-up period starts from the next day following the infusion of the study drug through 
Day 113 (± 7 days). Safety, efficacy, PK, immunogenicity, and biomarker assessments will be 
performed during the follow-up period as described in Appendix 1 and Appendix 2.  
7.4.1. 
End-of-Study Visit 
Patients who permanently discontinue from the study will be asked to return to the study center 
for the End-of-Study Visit, which is required to be conducted within 7 days after the premature 
study discontinuation. If the patient refuses to return for the End-of-Study Visit or are unable to 
do so, every effort should be made to contact the patient by telephone to determine their health 
status. 
7.4.2. 
Safety Follow-up Visit After Premature Study Discontinuation 
If patients discontinue the study within 30 days after study treatment, a Safety Follow-up Visit 
will be conducted at Day 31 (± 3 days) (30 days [± 3 days] after study treatment). If the 
premature discontinuation from study occurs within 7 days prior to Day 31 (± 3 days), the Safety 
Follow-up Visit can be combined with the End-of-Study Visit or Day 29 visit, as appropriate. 
7.4.3. 
Lost to Follow-up 
If attempts to contact the patient by telephone are unsuccessful, additional attempts should be 
made to obtain protocol-required follow-up information. Attempts of contact should be 
documented in the patient’s source documents. If a patient cannot be contacted despite all 
attempts, the patient will be considered lost to follow-up. 
7.5. 
Discontinuation From Study Treatment or From the Study 
7.5.1. 
Patient Discontinuation From Study Treatment 
Eligible patients will receive a complete dose of study drug. Patients have the right to 
discontinue study treatment infusion for any reason. In addition, the investigator has the right to 
discontinue a patient from study treatment. Patients who discontinue study treatment will remain 
on the study and continue to be followed for protocol-specified follow-up procedures 
(Appendix 1), if possible; this will include, but is not limited to, the safety assessments. 
The primary reason for discontinuation from study treatment should be documented on the 
appropriate eCRF. Patients may discontinue study treatment for reasons including but not limited 
to the following: 
x The investigator or sponsor determines it is in the best interest of the patient 
x Significant or persistent adverse event(s) 
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7.5.2. 
Patient Discontinuation From the Study (End of Study for an Individual Patient) 
Patients may discontinue from the study for reasons that include, but are not limited to, the 
following: 
x Patient withdrawal of consent 
x Study termination by sponsor 
x Lost to follow-up 
x Completion of all study assessments 
7.6. 
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 patient 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:  
x The incidence or severity of AEs in this or other studies indicates a potential health 
hazard to patients 
x Overall patient enrollment is unsatisfactory 
The sponsor will notify each investigator if a decision is made to terminate the study. Should this 
be necessary, prematurely discontinued patients must be seen for an End-of-Study Visit as 
described in Section 7.4.1. 
The investigators may be informed of additional procedures to be followed to ensure that 
adequate consideration is given to the protection of the patient’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. Patients will be closely 
monitored for safety and tolerability throughout the study. All assessments will be performed and 
documented in the medical record for each patient. 
The investigator and/or site personnel should use personal preventive equipment (PPE) 
appropriately when performing study assessments and procedures. PPE may be provided by the 
sponsor. The investigators should follow their hospital policy/local government policy of the 
country for the management of patient visits to the hospital. 
Where applicable, the study dosing will occur only if the clinical assessment and local laboratory 
test values (that must be available before study dosing) have been reviewed and found to be 
acceptable per protocol guidelines. 
8.1. 
Screening Assessments 
Screening evaluations will be performed within 3 days before the study drug administration 
(Appendix 1). Patients who agree to participate will sign the ICF before undergoing any 
study-specific screening assessment. The screening period begins on the first day that a screening 
assessment is conducted. The investigator is to assess patient eligibility according to the latest 
screening assessment results. Rescreening is not allowed. 
Results of laboratory tests (Section 8.2.3) performed before informed consent has been obtained 
DQG  3 days before the screening visit can be used for the purposes of screening. 
For the description of assessments that are conducted during screening as well as throughout the 
study, refer to Safety Assessments (Section 8.2) section. 
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 or surgery history; 
reproductive status (ie, of childbearing potential or no childbearing potential). 
All medications (eg, prescription drugs, over-the-counter drugs, herbal medications) used by the 
patient within 30 days prior to the single study dose will be recorded. 
8.1.2. 
Review of SARS-CoV-2 Test Result 
At screening, the investigator should review the positive results of SARS-CoV-2 test (RT-PCR 
or other tests authorized by local regulatory authorities) to confirm eligibility. 
8.2. 
Safety Assessments 
8.2.1. 
Vital Signs 
9LWDO VLJQV ZLOO LQFOXGH PHDVXUHPHQWV RI ERG\ WHPSHUDWXUH Û& SXOVH UDWH respiratory rate, 
SpO2, and blood pressure (systolic and diastolic). Pulse rate and blood pressure will be measured 
while the patient is in a seated or supine position after resting for 10 minutes. The monitoring 
frequency is detailed in Appendix 1. 
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Height will be measured at screening only and weight will be measured 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. 
8.2.3. 
Laboratory Safety Tests 
Local laboratory assessments of clinical chemistry, hematology, coagulation, and urinalysis will 
be conducted as outlined in Appendix 3 per the timepoints shown in Appendix 1. 
Samples for pregnancy testing will also be assessed. Urine pregnancy test using highly sensitive 
human chorionic gonadotropin will be performed in all women of childbearing potential per the 
timepoints specified in Appendix 1. A confirmation serum pregnancy test must be performed if 
the urine pregnancy test is positive or equivocal. Serum pregnancy tests may be substituted for 
urine pregnancy tests if the site is not able to perform urine testing. 
Additional tests may be performed at any time during the study as determined necessary by the 
investigator or required by local regulations.  
8.2.4. 
Electrocardiograms 
A 12-lead ECG will be performed at each timepoint specified in Appendix 1. For safety 
monitoring purposes, the investigator must review, sign, and date all ECG tracings. Paper or 
electronic copies of ECG tracings will be kept as part of the patient’s permanent study file at the 
site. 
All ECGs are to be obtained before other assessments scheduled at that same time (eg, vital sign 
measurements, blood draws). The patient 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. 
8.2.5. 
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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8.3. 
Efficacy Assessment 
8.3.1. 
Viral Load 
The nasopharyngeal swab, saliva, and blood samples will be collected at the timepoints shown in 
Appendix 1. The samples will be tested by the method of RT-qPCR in a central laboratory for 
the quantitative detection of nucleic acid from SARS-CoV-2.  
To obtain nasopharyngeal swab samples, insert minitip swab with a flexible shaft (wire or 
plastic) through the nostril parallel to the palate (not upwards) until resistance is encountered or 
the distance is equivalent to that from the ear to the nostril of the patient, indicating contact with 
the nasopharynx. Swab should reach depth equal to distance from nostrils to outer opening of the 
ear. Gently rub and roll the swab. Leave swab in place for several seconds to absorb secretions. 
Slowly remove swab while rotating it. Specimens can be collected from both sides using the 
same swab, but it is not necessary to collect specimens from both sides if the minitip is saturated 
with fluid from the first collection. If a deviated septum or blockage create difficulty in obtaining 
the specimen from one nostril, use the same swab to obtain the specimen from the other nostril. 
The process to collect saliva samples is defined in the laboratory manual. 
8.3.2. 
WHO 8-Point Ordinal Scale 
WHO 8-point ordinal scale will be used to assess clinical status of patients, at timepoints 
specified in Appendix 1 
Descriptor  
Score 
No clinical or virological evidence of infection 
0 
No limitation of activities  
1 
Limitation of activities  
2 
Hospitalized, no oxygen therapy 
3 
Oxygen by mask or nasal prongs 
4 
Non-invasive ventilation or high-flow oxygen  
5 
Intubation and mechanical ventilation 
6 
Ventilation and additional organ support-pressors, renal replacement 
therapy (RRT), extracorporeal membrane oxygenation (ECMO) 
7 
Death  
8 
 
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8.3.3. 
COVID-19-Related Symptoms and Disease Severity 
Investigators will assess if patients have recovered from COVID-19 based on symptoms. The 
COVID-19-related symptoms include, but are not limited to fever, cough, diarrhea, dizziness, 
rhinorrhea, anosmia, dysgeusia, sore throat, abdominal pain, anorexia, and vomiting. The 
assessments will be performed at the timepoints specified in Appendix 1. 
Investigator will assess the disease severity at each visit: 
Mild COVID-19 
x Positive testing by standard RT-PCR assay or equivalent test  
x Symptoms of mild illness with COVID-19 that could include fever, cough, sore throat, 
malaise, headache, muscle pain, gastrointestinal symptoms, without shortness of breath or 
dyspnea  
x No clinical signs indicative of Moderate, Severe, or Critical Severity  
Moderate COVID-19 
x Positive testing by standard RT-PCR assay or equivalent testing  
x Symptoms of moderate illness with COVID-19, which could include any symptom of 
mild illness or shortness of breath with exertion 
x Clinical signs suggestive of moderate illness with COVID-19, such as respiratory rate 
 20 breaths per minute, saturation of oxygen (SpO2) > 93% on room air at sea level, 
KHDUW UDWH   EHDWV SHU PLQXWH  
x No clinical signs indicative of Severe or Critical Illness Severity  
Severe COVID-19 
x Positive testing by standard RT-PCR assay or an equivalent test  
x Symptoms suggestive of severe systemic illness with COVID-19, which could include 
any symptom of moderate illness or shortness of breath at rest, or respiratory distress  
x Clinical signs indicative of severe systemic illness with COVID-19, such as respiratory 
UDWH   SHU PLQXWH KHDUW UDWH   SHU PLQXWH 6S22   RQ URRP DLU DW VHD OHYHO RU
PaO2/FiO2 < 300  
Note: For high altitude areas, PaO2/FiO2 ratio should be adjusted using formula: 
PaO2/[FiO2×(barometric pressure/760)]  
x No criteria for Critical Severity  
Critical COVID-19 
x Positive testing by standard RT-PCR assay or equivalent test  
x Evidence of critical illness, defined by at least one of the following:  
– Respiratory failure defined based on resource utilization requiring at least one of the 
following:  
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
Endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow 
nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at 
IORZ UDWHV !  /PLQ ZLWK IUDFWLRQ RI GHOLYHUHG R[\JHQ   QRQLQYDVLYH SRVLWLYH
pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (ie, clinical need 
for one of the preceding therapies, but preceding therapies not able to be administered in 
setting of resource limitation)  
– Shock (defined by systolic blood pressure < 90 mmHg, or diastolic blood pressure 
< 60 mmHg or requiring vasopressors)  
– Multi-organ dysfunction/failure  
8.4. 
Pharmacokinetic Assessment and Antidrug Antibody Testing 
Blood will be collected to characterize the PK of BGB-DXP593 concentrations using validated 
immunoassays. Blood samples will be collected for characterization of ADAs. 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 Appendix 2. 
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. 
8.5. 
Biomarkers 
Peripheral blood and/or saliva samples will be collected from patients at different timepoints 
specified in the Schedule of Assessments (Appendix 1) to explore the association of biomarkers 
with the efficacy of BGB-DXP593, including but not limited to, SARS-CoV-2 mutations, 
serology, cytokines and gene expression signatures. 
Saliva samples will be collected at various timepoints for testing SARS-CoV-2 mutations to 
explore the association of potential mutations on the genomic region of the virus with the 
efficacy of BGB-DXP593. 
Blood samples will be collected from patients on Day 1 before study drug administration for 
measurement of SARS-CoV-2 serology levels at baseline. Additional blood samples will also be 
collected at various timepoints before and after study drug administration for the measurement of 
potential biomarkers in peripheral blood including but not limited to cytokines and gene 
expression levels, for the exploration of the association of these biomarkers with the efficacy of 
BGB-DXP593. 
Shipping, storage, and handling of blood or saliva samples for the assessment of biomarkers will 
be managed through a central laboratory. Refer to the laboratory manual for details of sample 
handling and the Schedule of Assessments (Appendix 1) for sample collection timepoints. 
Blood samples will be individually processed and stored as described in the laboratory manual. 
Coded archival samples may be used for additional medical and/or scientific research that are 
outside of the current study purpose and objectives (but always in compliance with applicable 
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law). The research may relate to the diseases that are the subject of this study, validation of new 
techniques/assays, and/or associated potential medicines. This may include research to help 
developing ways to detect, monitor, or treat the target disease of this study. 
8.6. 
Visit Windows 
A visit window of ± 1 day is allowed for visits at Day 5, Day 8, and Day 15, ± 2 days is allowed 
for visits at Day 22 and Day 29, ± 3 days is allowed for visits at Day 57 and Day 85, and 
± 7 days is allowed for visits at Day 113 (Appendix 1 and Appendix 2). All assessments will be 
performed on the day of the specified visit unless an acceptable time window is specified. 
8.7. 
Unscheduled Visits 
Unscheduled visits may be performed at any time at the patient’s or the investigator’s request. 
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 
entered 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 
No clinical data are available yet and no risk associated with BGB-DXP593 has been identified. 
No treatment-related toxicity was noted in monkeys at weekly repeated doses up to 300 mg/kg in 
the 14-day repeat dose study in monkeys. 
9.2. 
General Plan to Manage Safety Concerns 
9.2.1. 
Eligibility Criteria 
Eligibility criteria were selected to guard the safety of patients in this study. Results from the 
nonclinical toxicology studies with BGB-DXP593, as well as the nonclinical/clinical data from 
other SARS-CoV-2 neutralizing mAbs were considered. Patients with any history of a severe 
allergic reaction that has a reasonable risk of recurrence are 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 patients will be evaluated clinically and with standard laboratory tests at regular 
intervals during their participation in this study. Safety evaluations will consist of medical 
interviews, recording of AEs (see Section 9.6), physical examinations, laboratory measurements 
(hematology, clinical chemistry, etc), and other assessments including those listed in 
Appendix 1. 
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 (for 
additional information, see Section 5.2). 
Blood samples will be drawn for determination of ADAs to BGB-DXP593 in patients who have 
received the study drug.  
Investigators are instructed to report all AEs (includes pregnancy-related AEs). 
The potential safety issues anticipated in this study, as well as measures intended to avoid or 
minimize such toxicities, are outlined in Section 9.7. 
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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 the study drug or not. 
Examples of AEs include:  
x 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 
x Detection or diagnosis of a new condition after study drug administration even though the 
condition might have been present before the start of the study 
x Signs, symptoms, or the clinical sequelae of a suspected interaction 
x 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 this instance, all patient identifiers will be blinded on the 
copies of the medical records before submission to the sponsor. 
9.3.2. 
Assessment of Severity 
The investigator will assess the severity for each AE and SAE reported during the study. AEs 
and SAEs should be assessed and graded based upon NCI-CTCAE Version 5.0. 
Toxicities that are not specified in NCI-CTCAE will be defined as follows: 
x Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
x Grade 2: Moderate; minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living 
x Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
activities of daily living 
x Grade 4: Life-threatening consequences; urgent intervention indicated 
x Grade 5: Death related to AE 
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Note: The terms “severe” and “serious” are not synonymous. Severity is a measure of intensity 
(eg, 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 
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. 
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 
consult the BGB-DXP593 Investigator’s Brochure in the determination of his/her assessment. 
There may be situations when an 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 before 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” based on all information available at the time of reporting. 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: 
x Temporal relationship of the AE to the administration of study treatment/study procedure 
x Whether an alternative etiology has been identified 
x Mechanism of action of the study drug 
x Biological plausibility 
x An AE should be considered “related” to study drug if any of the following criteria 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 patient’s 
clinical condition or other concomitant AEs). 
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9.3.4. 
Follow-up of Adverse Events 
After the initial AE or SAE report, the investigator is required to proactively follow each patient 
and provide further information to the sponsor on the patient’s condition. 
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 patient is lost to follow-up, or the patient 
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 patient dies during participation in the 
study or during a recognized follow-up period, the sponsor will be provided with a copy of any 
postmortem findings, including histopathology. 
New or updated information should be reported to the sponsor according to the SAE instructions 
provided by the sponsor within the timeframes outlined in Section 9.6.2. 
9.3.5. 
Laboratory Test Abnormalities 
Abnormal laboratory findings (eg, clinical chemistry, complete blood count, coagulation, or 
urinalysis) or other abnormal assessments (eg, ECGs 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 the laboratory test abnormalities or other 
abnormal assessments that: 
x are associated with clinical signs or symptoms, or  
x require active medical intervention, or  
x lead to treatment interruption or discontinuation, or 
x require close observation, more frequent follow-up assessments, or further diagnostic 
investigation. 
If a clinically significant laboratory abnormality is a sign of a disease or syndrome (eg, alkaline 
phosphatase and bilirubin 5 x ULN associated with cholestasis), only the diagnosis 
(ie, cholestasis) should be recorded on the AE eCRF. 
If the laboratory abnormality can be characterized by a precise clinical term per standard 
definitions, the clinical term should be recorded as the AE. For example, an elevated serum 
potassium level of 7.0 mEq/L should be recorded as “hyperkalemia.” 
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Observations of the same clinically significant laboratory abnormality from visit to visit should 
not be repeatedly recorded on the AE eCRF, unless the etiology changes. The initial severity of 
the event should be recorded, and the severity or seriousness should be updated any time the 
event worsens. 
9.4. 
Definition of a Serious Adverse Event 
An SAE is any untoward medical occurrence that, at any dose: 
x Results in death 
x Is life-threatening 
Note: The term “life-threatening” in the definition of “serious” refers to an AE in 
which the patient was at risk of death at the time of the AE. It does not refer to an AE 
that hypothetically might have caused death if it was more severe. 
x Requires hospitalization or prolongation of existing hospitalization 
Note: In general, hospitalization signifies that the patient 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. 
x 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 with or prevent everyday life functions but do not constitute a substantial 
disruption. 
x Is a congenital anomaly/birth defect 
x Is considered a significant medical AE by the investigator based on medical judgement 
(eg, may jeopardize the patient or may require medical/surgical intervention to prevent 
one of the outcomes listed above) 
The following are NOT considered to be SAEs: 
x Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline 
x Hospitalization for social/convenience considerations 
x Scheduled therapy for the target disease of the study, including admissions for PK 
sampling or convenience 
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9.5. 
Suspected Unexpected Serious Adverse Reaction 
A suspected unexpected serious adverse reaction is a serious adverse reaction that is both 
unexpected (ie, not present in the study drug’s reference safety information) and meets the 
definition of a serious adverse drug reaction, 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 Recording Period 
After informed consent has been signed but before 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 study treatment or End-of-Study Visit, whichever is later. After 
the period, the investigator should report any SAEs that are considered to be related to the study 
drug. 
For the follow-up period for AEs, see Section 9.3.4. 
9.6.2. 
Reporting 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 an SAE, the 
event must be reported promptly (within 24 hours) to the sponsor or designee as described in 
Table 2. 
Table 2: 
Timeframes and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee 
 
Timeframe for 
sending 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 an SAE has occurred in a patient, he/she is to report the 
information to the sponsor within 24 hours, as outlined above in Section 9.6.2.1. The SAE report 
will always be completed as thoroughly as possible, including all available details of the event 
and forwarded to the sponsor or designee within the designated timeframes. 
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If the investigator does not have all information regarding an 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 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 drug 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 suspected unexpected serious adverse reactions (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. 
9.6.3. 
Eliciting Adverse Events 
The investigator or designee will ask patients about AEs by asking the following standard 
questions: 
x How are you feeling? 
x Have you had any medical problems since your last visit? 
x Have you taken any new medicines since your last visit? 
9.6.4. 
Deaths 
Death is an outcome and not usually considered an AE. If the only information available is death 
and the cause of death is unknown, then the death is reported as an AE (eg, “death,” “death of 
unknown cause,” or “death unexplained”). 
9.6.5. 
Recording Pregnancies 
If a female patient or the partner of a male patient becomes pregnant within 30 days after the 
single dose of study drug, a pregnancy report form must 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. 
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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 always be reported as an 
SAE. Similarly, any congenital anomaly/birth defect in a child born to a patient exposed to the 
study drug should be recorded and reported as an SAE. 
9.6.6. 
Expedited Reporting to Health Authorities, Investigators, Institutional Review 
Boards, and Independent 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 safety information documents: 
x BGB-DXP593 Investigator’s Brochure 
9.6.7. 
Recording 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. 
9.7. 
Management of Infusion-Related Reactions and Severe 
Hypersensitivity 
As a routine precaution, following completion of study drug(s) administration, patients 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 for 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 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, and cardiogenic shock. 
Patients should be closely monitored for infusion-related reactions. Immediate access to an ICU 
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 study drug(s) are 
provided in Table 3. 
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Table 3: 
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 
IRU  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 patient 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 patient should be withdrawn from study drug 
treatment. 
Grade 4 – life-threatening 
Life-threatening consequences; urgent intervention 
indicated. 
Immediately stop the infusion. Proper medical 
management should be instituted as described below. 
The patient 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 patient 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). Patients should be instructed to report any delayed reactions to the investigator 
immediately. 
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In the event of a systemic anaphylactic/anaphylactoid reaction, the infusion must be stopped 
immediately and the patient 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 patient will be administered epinephrine injection and dexamethasone infusion if 
hypersensitivity reaction is observed. The patient should then be placed on monitor immediately 
and an ICU should be alerted for possible transfer if needed. 
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10. 
STATISTICAL METHODS AND SAMPLE SIZE 
DETERMINATION 
A statistical analysis plan (SAP) will be prepared and finalized prior to database lock. This 
document will provide further details regarding the definition of analysis variables and analysis 
methodology to address all study objectives. Any deviations in the planned analysis as stated in 
the protocol will be delineated in the SAP. Any deviations from the SAP will be reported in the 
clinical study report. A data review will be conducted prior to database lock. 
10.1. 
Statistical Analysis 
10.1.1. 
Analysis Sets 
The Intent-to-Treat (ITT) Analysis Set includes all randomized patients. Patients will be 
analyzed according to the treatment assigned at randomization. This will be the primary analysis 
set for efficacy analyses. 
The Safety Analysis Set includes all patients who have received the study drug (BGB-DXP593 
or placebo). Patients will be analyzed according to their actual treatment received. The Safety 
Analysis Set will be used for all safety analyses. 
The PK Analysis Set includes all patients who have received the study drug (BGB-DXP593) per 
the protocol and for whom any postdose PK data are available. 
The ADA Analysis Set includes all the patients who have received the study drug and in whom 
both baseline ADA and at least 1 postbaseline ADA results are available. 
10.1.2. 
Randomization Methods 
Patients will be randomized using the IRT system with allocation ratio of 1:1:1:1 to placebo, 
BGB-DXP593 at 5 mg/kg, BGB-DXP593 at 15 mg/kg, and BGB-DXP593 at 30 mg/kg. Patient 
randomization will be stratified by country and disease severity (mild versus moderate 
COVID-19). 
10.1.3. 
Patient Disposition 
The number of patients randomized, treated, discontinued from study drug and/or the study will 
be counted. The primary reason for study drug and/or study discontinuation will be summarized 
according to the categories in the eCRF. 
Important protocol deviations will be summarized and listed by category. 
10.1.4. 
Demographic and Other Baseline Characteristics 
Demographic and other baseline characteristics will be summarized using the ITT Analysis Set 
and descriptive statistics. Continuous variables include but are not limited to age, weight, and 
height. Categorical variables include but are not limited to gender, geographical region, and race. 
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10.1.5. 
Prior and Concomitant Medications 
Prior medications will be defined as medications that stopped before the administration of study 
drug. Concomitant medications will be defined as medications that 1) started before the 
administration of study drug and were continuing at the time of the administration of study drug, 
or 2) started on or after the date of the administration of study drug up to 30 days after dosing. 
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
drug codes and will be further coded to the appropriate Anatomical Therapeutic Chemical code 
indicating therapeutic classification. Prior and concomitant medications will be summarized and 
listed by drug and drug class. A listing of prior and concomitant medications will be provided. 
10.2. 
Efficacy Analyses 
10.2.1. 
Primary Endpoint Analyses 
The statistical hypotheses to be tested for the primary endpoint are as follows: 
H0: there is a flat dose response curve comparing change from baseline to Day 8 in SARS-CoV-2 
viral shedding in the placebo and the BGB-DXP593 dose groups 
H1: there is a non-flat dose response curve indicating a benefit of BGB-DXP593 over placebo 
A Mixed Model Repeated Measures (MMRM) analysis will be used to analyze the primary 
endpoint of change from baseline to Day 8 in SARS-CoV-2 viral shedding. This model will 
include treatment, visit, and disease severity as discrete fixed effects; baseline viral shredding as 
a continuous fixed effect; and interaction between visit and treatment, interaction between visit 
and baseline, interaction between visit and disease severity, and patient as a random effect. The 
primary treatment comparisons will be the contrast between treatments at Day 8. 
The analysis will be carried out and covariate-adjusted fixed effect estimates of average response 
for each treatment and the covariance matrix will be extracted from the fit and used for multiple 
comparison procedures and modelling approaches (MCPMod) analysis. 
The primary analysis uses methodology for dose finding employing both multiple comparison 
procedures and modelling techniques. The MCPMod procedure allows for simultaneous 
evaluation of different potential dose response patterns, whilst protecting the overall probability 
of Type I error (one-VLGHG Į RI  
For the hypothesis testing and for the sample size calculation, the basic shape of each of the 
models to be tested must be predefined. The following models will be considered for this 
analysis: linear, Emax, SigEmax and quadratic.  
The model assumptions and resulting graphs were selected to cover both plausible and a diverse 
range of dose response patterns. These are shown in Figure 3. The parameters for each model 
shape are listed in Table 4. 
 
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Figure 3: 
Shape of the Considered Dose Response Patterns for the MCPMod Analysis 
Abbreviation: MCPMod, multiple comparison procedures and modelling approaches 
Table 4: 
Parameter(s) in Each Model 
Model 
Prespecified parameters 
Emax1 
ED50   2.6 
Emax2 
ED50   12.5 
sigEmax 
ED50   K   4 
Quadratic 
į  -0.022 
Linear 
No assumption needed 
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If at least one model is statistically significant, then we will reject the null hypothesis of a flat 
dose response relationship over viral shredding change at Day 8, with a multiple contrast test 
controlled for the family-wise type I error rate at one-VLGHG Į   
After rejecting the null hypothesis, the statistically significant model(s) from the above candidate 
set are selected as reference models. The dose-response relationship is estimated using model 
average technique to generate the new estimates. 
The target dose(s) can be estimated from the average model by incorporating information on the 
minimum clinically relevant effect and by accounting for safety. 
Comparisons of active doses to placebo (90% confidence intervals [CIs] and p-values) based on 
the mixed effects model will be reported. These are supportive analyses of the primary endpoint 
to supplement the MCPMod analysis, which is the primary analysis. 
10.2.2. 
Secondary Endpoint Analyses 
Secondary efficacy endpoints will include: 
x Time-weighted average change in viral shedding as measured by RT-qPCR in 
nasopharyngeal swab samples from baseline to Day 15 
x Change in SARS-CoV-2 viral shedding as measured by RT-qPCR in nasopharyngeal 
swab samples from baseline to Day 15 
x Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR 
in any tested samples 
x Proportion of patients requiring hospitalization due to worsened COVID-19 
x Time to resolution of all COVID-19-related symptoms 
x All-cause mortality rate at Day 29 
The time-weighted average change in viral shedding as measured by RT-qPCR in 
nasopharyngeal swab samples from baseline to Day 15 is defined as: 
σ
[0.5 × (ܻ௜+ ܻ௜ାଵ) × (ݐ௜ାଵെݐ௜)]
௕ିଵ
௜ୀ௔
ݐ௕െݐ௔
 
where ܻ௜ is the change from baseline in viral shedding at Visit ݅, ݐ is the time at the specified 
timepoint (the actual study day), ܽ is the baseline assessment at Day 1, and ܾ is the last 
assessment at or prior to Day 15 visit. Analysis of covariance (ANCOVA) model with 
corresponding baseline viral shedding, disease severity, and treatment as covariates will be used. 
Comparisons of active doses to placebo (90% CIs and p-values) will be provided.  
The same MMRM analysis for primary endpoint will be used to analyze the change in SARS-
CoV-2 viral shedding from baseline to Day 15. Comparisons of active doses to placebo (90% CIs 
and p-values) will be provided. 
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Kaplan-Meier method will be used to assess the time to negative RT-qPCR. The corresponding 
quartiles (including the median) will be reported and a two-sided 95% CI of median, if 
estimable, will be constructed with a generalized Brookmeyer and Crowley method for each 
dosing group. Patients who have died prior to experiencing the event of interest will be censored 
on the day of data cutoff. 
The number of patients who require hospitalization due to worsened COVID-19 will be counted. 
Corresponding proportion will be derived and a two-sided binomial exact 95% CI of proportion 
will be constructed.  
Kaplan-Meier method will be used to assess the time to resolution of all COVID-19-related 
symptoms. The corresponding quartiles (including the median) will be reported and a two-sided 
95% CI of median, if estimable, will be constructed with a generalized Brookmeyer and Crowley 
method for each dosing group. Patients who have died prior to experiencing the event of interest 
will be censored. Their follow-up length will be arbitrarily set as (data cutoff date – 
first-patient-in date). This approach is to count death as the worst possible outcome without 
possibility of recovery. 
Kaplan-Meier method will be used to assess all-cause mortalities and corresponding quartiles 
(including the median) will be reported. A two-sided 95% CI of median, if estimable, will be 
constructed with a generalized Brookmeyer and Crowley method. Patients who does not die will 
be censored on the last known date alive.  
10.2.3. 
Exploratory Endpoint Analyses 
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Safety will be determined by monitoring AEs and laboratory values (hematology, clinical 
chemistry, coagulation, and urinalysis). Vital signs, physical examinations, and ECG findings 
will also be used in determining the safety profile. The severity of AEs will be graded according 
to NCI-CTCAE Version 5.0. The incidence of TEAEs will be reported as the number 
(percentage) of patients with TEAEs by Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class and preferred term. Descriptive summary statistics (eg, n, mean, 
standard deviation, median, minimum, and maximum for continuous variables; n [%] for 
categorical variables) and changes from baseline will be determined for laboratory parameters 
and vital signs. 
Safety data will be summarized using the Safety Analysis Set. 
10.3.1. 
Extent of Exposure 
Extent of exposure to each study drug will be summarized descriptively for the total dose 
received per patient (mg) and relative dose intensity. 
The number (percentage) of patients requiring treatment interruption because of AEs will be 
summarized for each study drug. Reasons for dose interruption will be summarized as well. 
Patient data listings will be provided for all dosing records and for calculated summary statistics. 
10.3.2. 
Adverse Events 
The AE verbatim descriptions (investigator’s description from the eCRF) will be coded using 
MedDRA. AEs will be coded to MedDRA lowest level term, preferred term, and primary system 
organ class. 
A TEAE is defined as an AE that had an onset date or a worsening in severity from baseline 
(pretreatment) on or after the administration of study drug and up to the 30 days after dosing. 
The incidence of TEAEs will be reported as the number (percentage) of patients with TEAEs by 
system organ class and preferred term. A patient will be counted only once by the highest 
severity grade per NCI-CTCAE Version 5.0 within a system organ class and preferred term, even 
if the patient experienced more than 1 TEAE within a specific system organ class and preferred 
term. The number (percentage) of patients with TEAEs will also be summarized by relationship 
to the study drug. 
Treatment-related TEAEs include those events considered by the investigator to be related to 
VWXG\ WUHDWPHQW RU ZLWK PLVVLQJ DVVHVVPHQW RI WKH FDXVDO UHODWLRQVKLS 6$(V GHDWKV  Grade 3 
TEAEs, treatment-related TEAEs, and TEAEs that led to treatment discontinuation or treatment 
interruption will be summarized. 
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10.3.3. 
Laboratory Analyses 
Clinical laboratory (eg, hematology, clinical chemistry, 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. Reference (normal) 
ranges for laboratory parameters will be provided. Descriptive summary statistics (eg, n, mean, 
standard deviation, median, minimum, and maximum for continuous variables; n [%] for 
categorical variables) for laboratory parameters and their changes from baseline will be 
calculated. Laboratory values will be summarized by visit and by visit with the maximum 
postbaseline change. 
Laboratory parameters that are graded by NCI-CTCAE Version 5.0 or higher will be 
summarized by NCI-CTCAE grade. In the summary of laboratory parameters by NCI-CTCAE 
grade, parameters with NCI-CTCAE grading in both high and low directions will be summarized 
separately. 
10.3.4. 
Vital Signs 
Descriptive statistics for vital sign parameters (systolic and diastolic blood pressure, pulse rate, 
and body temperature) and changes from baseline will be presented by visit for all visits. Vital 
signs will be listed by patient and visit. 
10.4. 
Pharmacokinetic Analyses 
The PK analyses will include patients with sufficient data to enable estimation of key 
parameters, such as Cmax, tmax, t1/2, AUCt, AUCinf, AUC0-29, CL, and Vz (as appropriate for data 
collected), with patients grouped according to treatment received. Non-compartmental or 
model-based methods will be used as appropriate. 
Individual and mean serum BGB-DXP593 concentration versus time data will be tabulated and 
plotted by dose level. The PK parameters of BGB-DXP593 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 patients who develop detectable ADAs. The incidence of positive ADAs and 
neutralizing ADAs will be reported for evaluable patients. The effect of immunogenicity on PK 
and safety may be evaluated if data allow. 
10.6. 
Other Exploratory Analyses 
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10.7. 
Sample Size Consideration 
The sample size calculation is based on the following assumptions: 
x The primary endpoint “change from baseline to Day 8 in SARS-CoV-2 viral shedding” is 
normally distributed 
x One-sided significance level Į   
x True maximum treatment effect size of BGB-DXP593 versus placebo is -1.5 log10 copies 
per mL 
x Standard deviation is 3.2 log10 copies per mL (Wang et al 2020) 
x Prespecified candidate models listed in Section 10.2.1  
Forty-one patients are needed with primary endpoint data per arm to provide at least 82% power 
to detect non-flat dose-response relationship. MCPMod approach is used. In order to ensure 
41 patients per arm with primary endpoint data, at least 43 patients per arm need to be 
randomized. 
The calculation has been performed using R software, version 3.6.1. 
10.8. 
Interim Analyses 
A primary analysis is planned after all patients have finished Day 8 visit or discontinued the 
study earlier. A decision will be made based on the interim results about whether a Phase 3 study 
should be initiated and which dose to be used for the Phase 3 study. 
10.9. 
Missing Data Handling and Censoring Rules 
In general, values for missing data will not be imputed, unless methods for handling missing data 
are specified.  
For MMRM analysis, no imputation will be performed for missing viral shredding. If a patient 
misses a visit, the missing data will not be imputed. The mixed effect model will handle missing 
data based on a likelihood method under the "missing at random” assumption.  
Sensitivity analyses using method of last observation carry forward (LOCF) may be considered 
to assess the potential impact from missing data, which will be detailed in the statistical analysis 
plan (SAP). 
Missing dates or partially missing dates will be imputed conservatively for adverse events and 
prior/concomitant medications/procedures. Specific rules for handling of missing or partially 
missing dates for adverse events and prior/concomitant medications/procedures will be provided 
in the statistical analysis plan (SAP). 
Censoring rules for analyses of time-to-event endpoints are determined as in Table 5. 
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Table 5: 
Censoring Rules for Analysis of Time-to-event Endpoints 
No. 
Situation 
Date of Event or Censoring 
Outcome 
1 
Target event documented 
Date of occurrence of target event 
Event 
2 
Multiple target events documented 
Date of first occurrence of target event 
Event 
3 
No target event or death occurred by the time 
of the End-of-Study Visit or the Safety Follow-
up Visit (whichever is later), or data cut-off, or 
withdrawal from study, whichever comes first 
Date of last adequate event assessment 
prior to or on the date of the 
End-of-Study Visit or the Safety 
Follow-up Visit (whichever is later), or 
data cut-off, or withdrawal from study, 
whichever comes first 
Censored 
4 
Death and no target event prior to death 
Date of data cutoff 
Censored 
 
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11. 
STUDY COMMITTEES 
11.1. 
Independent Data Monitoring Committee  
An IDMC will be established; the function and membership will be described in the IDMC 
Charter. 
Regular safety monitoring and efficacy monitoring will be performed by the IDMC. The first 
IDMC safety review will occur after at least 12 patients (ie, approximately 3 patients per 
treatment arm) have received study treatment and have been followed up for at least 7 days. The 
frequency of the subsequent safety reviews will be defined in the IDMC Charter. Preliminary 
efficacy summaries will be provided to the IDMC when approximately 60 patients have received 
study treatment and have been followed up for at least 14 days. Preliminary efficacy summaries 
will be included in the IDMC report and reported monthly afterwards. The frequency of the 
meetings may be adjusted based on the need for safety monitoring of the study. The IDMC has 
access to unblinded information to assess the safety and efficacy. 
In addition to the planned IDMC review(s), ad hoc reviews may take place based on new 
information. 
The IDMC may recommend modifications to the study procedures or conduct based on available 
data. After IDMC review and discussion, the sponsor will make all final decisions regarding any 
change in study conduct. Please see the details in the IDMC Charter. 
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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 patient 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 patient 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, Ltd., (hereafter referred to as 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, 
patients’ 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) is responsible for ensuring adequate 
accountability of all used and unused study drug(s). This includes acknowledgment of receipt of 
each shipment of study drug(s) (quantity and condition), patient drug dispensation records, and 
returned or destroyed study drug(s). Dispensation records will document quantities received from 
BeiGene’s designated depot or its designee and quantities dispensed to patients, including 
batch/lot number, date dispensed, patient 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 unblinded 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 unblinded monitor over the course of the study. 
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14. 
ETHICS/PROTECTION OF HUMAN PATIENTS 
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 patient. 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 patient, and relevant supporting 
information must be submitted, reviewed, and approved by the IRB/IEC before the study is 
initiated. In addition, any patient 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 patients 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 patients 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 patient or the patient’s legally authorized 
representative before his or her participation in the study. The case history or clinical records for 
each patient 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 patient to participate. The 
final revised IRB/IEC-approved consent forms must be provided to the sponsor for health 
authority submission purposes. 
Patients 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 patient 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 patient or the patient’s legally authorized 
representative. All signed and dated ICFs must remain in each patient’s study file or in the site 
file and must be available for verification by study monitors at any time. 
14.4. 
Patient 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 patients’ personal and medical information. 
The principal investigator shall code the medical information obtained during the study with a 
unique patient identification number assigned to each patient enrolled in the study. This approach 
ensures that patients’ names are not included in any data set transmitted to any sponsor location. 
Patient 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 patient), unless permitted or 
required by law. 
In the event of a breach of the confidentiality of a patient’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 patient’s personal physician or other appropriate medical 
personnel responsible for the patient’s welfare for treatment purposes. 
Data generated during this study must be available for inspection upon request by representatives 
of the United States Food and Drug Administration and all other national and local health 
authorities; by sponsor monitors, representatives, and collaborators; and by the IRBs/IECs for 
each study site, as appropriate. 
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The investigator must ensure that patients’ 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 BGB-DXP593 Investigator’s 
Brochure, 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 patient, 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 patient 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 will make site visits to review protocol compliance, compare 
eCRFs against individual patient’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 patient 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, preferred term, and primary 
system organ class. 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) patient 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. 
Patient 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: patient 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 patient, 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 patient 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. 
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15.5. 
Study and Study Center Closure 
Upon completion of the study, the unblinded monitor will conduct the following activities in 
conjunction with the investigator or study center personnel, as appropriate: 
x Return/provide all study data to the sponsor 
x Resolution and closure of all data queries 
x Accountability, reconciliation, and arrangements for unused study drug(s) 
x Review of study records for completeness 
x Collection of all study documents for the trial master file filing according to GCP and 
local regulation 
x 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(s) 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. 
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All information provided by the sponsor and all data and information generated by the study 
center as part of the study (other than a patient’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. 
These restrictions do not apply to: 
x Information that becomes publicly available through no fault of the investigator or study 
center personnel 
x Information that is necessary to disclose in confidence to an IEC/IRB solely for the 
evaluation of the study 
x Information that is necessary to disclose to provide appropriate medical care to a patient 
x 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 
Arvin AM, Fink K, Schmid MA, et al. A perspective on potential antibody-dependent 
enhancement of SARS-CoV-2. Nature. 2020;584(7821):353-63. 
BeiGene Investigator’s Brochure, BGB-DXP593. Edition 1.0, July 2020. 
Bryan A, Fink SL, Gattuso MA, et al. Anti-SARS-CoV-2 IgG antibodies are associated with 
reduced viral load. medRxiv. Preprint posted online May 24, 2020. doi: 
10.1101/2020.05.22.20110551 
Baum A, Fulton BO, Wloga E, et al. Antibody cocktail to SARS-CoV-2 spike protein prevents 
rapid mutational escape seen with individual antibodies. Science. 2020;369(6506):1014-8. 
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. 
Clinical Trials Facilitation Group (CTFG). Recommendations related to contraception and 
pregnancy testing in clinical trials. September 15, 2014. 
http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf 
COVID-19 Treatment Guidelines Panel. Coronavirus Disease 2019 (COVID-19) Treatment 
Guidelines. National Institutes of Health. Available at 
https://www.covid19treatmentguidelines.nih.gov/. Accessed 04 August 2020. 
Eigenmann MJ, Karlsen TV, Krippendorff BF, et al. Interstitial IgG antibody pharmacokinetics 
assessed by combined in vivo- and physiologically-based pharmacokinetic modelling 
approaches. J Physiol. 2017;595(24):7311-30. 
Fajnzylber J, Regan James, Coxen K, et al. SARS-CoV-2 viral load is associated with increased 
disease severity and mortality. Preprint posted online July 17, 2020; doi: 
10.1101/2020.07.15.20131789 
Hart TK, Cook RM, Zia-Amirhosseini P, et al. Preclinical efficacy and safety of mepolizumab 
(SB-240563), a humanized monoclonal antibody to IL-5, in cynomolgus monkeys. J Allergy 
Clin Immunol. 2001;108(2):250-7. 
Hershberger E, Sloan S, Narayan K, et al. Safety and efficacy of monoclonal antibody VIS410 in 
adults with uncomplicated influenza A infection: Results from a randomized, double-blind, 
phase-2, placebo-controlled study. EBioMedicine. 2019;40:574-82.  
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 08 August 2017. 
Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: The reality and challenges. J 
Microbiol Immunol Infect. 2020;53:436-43. 
Joyner MJ, Bruno KA, Klassen SA, et al. Safety update: COVID-19 convalescent plasma in 
20,000 hospitalized patients. Mayo Clin Proc. 2020;95(9):1888-97. 
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Khurshid Z, Zohaib S, Joshi C, et al. Saliva as a non-invasive sample for the detection of SARS-
CoV-2: a systematic review. medRxiv. Preprint posted online May 13, 2020; doi: 
10.1101/2020.05.09.20096354 
Korber B, Fischer WM, Gnanakaran S, et al. Tracking changes in SARS-CoV-2 spike: evidence 
that D614G increases infectivity of the COVID-19 virus. Cell. 2020;182(4):P812-27. 
Li Q, Wu J, Nie J, et al. The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and 
Antigenicity. Cell. Preprint posted online July 17, 2020; doi.org/10.1016/j.cell.2020.07.012. 
Pujadas E, Chaudhry F, McBride R, et al. SARS-CoV-2 viral load predicts COVID-19 mortality. 
medRxiv. Preprint posted online June 12, 2020; doi: 10.1101/2020.06.11.20128934. 
Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions--guidelines 
for healthcare providers. Resuscitation. 2008;77(2):157-69. 
Shah DK, Betts AM. Antibody biodistribution coefficients: inferring tissue concentrations of 
monoclonal antibodies based on the plasma concentrations in several preclinical species and 
human. MAbs. 2013;5(2):297-305. 
Sullivan HC, Roback JD. Convalescent plasma: therapeutic hope or hopeless strategy in the 
SARS-CoV-2 pandemic. Transfus Med Rev. 2020;S0887-7963(20)30025-0. doi: 
10.1016/j.tmrv.2020.04.001. 
Tay MZ, Poh CM, Rénia L, et al. The trinity of COVID-19: immunity, inflammation and 
intervention. Nat Rev Immunol. 2020;20:363-74. 
Walls AC, Park YJ, Tortorici MA, et al. Structure, Function, and Antigenicity of the SARS-
CoV-2 Spike Glycoprotein. Cell. 2020;181(2):281-92.e6. 
Wang Y, Zhang D, Du G, et al. Remdesivir in adults with severe COVID-19: a randomised, 
double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395(10236):1569-78. 
Wölfel R, Corman VM, Guggemos W, et al. Virological assessment of hospitalized patients with 
COVID-2019. Nature. 2020;581(7809),465-9. 
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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17. 
APPENDICES 
 
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b Telehealth/remote nurse home visits will be permitted after Day 1 visit (treatment)/discharge from the hospital if circumstances prevent visits to the clinic. 
Day 5, Day 22, and Day 57 visits will be performed by phone/video. 
c The EOS Visit will be conducted within 7 days after a premature study discontinuation. The Day 113 visit is the EOS Visit for patients who complete all the 
previously planned study visits. 
d The Safety Follow-up Visit is only for patients who prematurely discontinue the study within 30 days after study treatment. The Safety Follow-up Visit will be 
conducted at 30 days (± 3 days) after study treatment (Day 31 [± 3 days]). If the premature discontinuation from study occurs within 7 days prior to Day 31 
(± 3 days), the Safety Follow-up Visit can be combined with the EOS Visit or the Day 29 visit, as appropriate. 
e Written 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 (IEC)/Institutional Review Board (IRB). The consent can be obtained via remote consent if approved by local 
IRB. 
f Follicle-stimulating hormone (FSH) and estradiol assessments will be performed in female patients who are < 55 years of age with no spontaneous menses for 
 12 months to identify the status of no childbearing potential (refer to Appendix 4). Historical test results are allowed. 
g Positive results of SARS-CoV-2 test (RT-PCR or other tests authorized by local regulatory authorities)  72 hours prior to screening are required for 
confirmation of eligibility. 
h Patients enrolled will be randomized via IRT to receive placebo, BGB-DXP593 5 mg/kg, BGB-DXP593 15 mg/kg, or BGB-DXP593 30 mg/kg on Day 1. 
i The dose of BGB-DXP593 will be based on the patient’s actual body weight on the day of receiving the study drug (Day 1). 
j Vital signs will be monitored approximately every 15 minutes during the infusion, and then hourly till 2 hours after the infusion; the monitoring will include 
PHDVXUHPHQWV RI ERG\ WHPSHUDWXUH Û& SXOVH UDWH respiratory rate, saturation of oxygen (SpO2), and blood pressure (systolic and diastolic). Pulse rate and 
blood pressure will be measured while the patient is in a seated or supine position after resting for 10 minutes. Height will be measured at screening only and 
weight will be measured at Day 1 before study drug dosing. 
k 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.  
l At subsequent visits (and as clinically indicated), limited, symptom-directed physical examinations will be performed. 
m A 12-lead ECG will be performed at the timepoints specified in the table. All ECGs are to be obtained before other assessments scheduled at that same time 
HJ YLWDO VLJQ PHDVXUHPHQWV EORRG GUDZV 7KH SDWLHQW VKRXOG UHVW LQ D VHPLUHFXPEHQW RU VXSLQH SRVLWLRQ IRU   PLQXWHV LQ the absence of environmental 
distractions that may induce changes in heart rate (eg, television, radio, conversation) before each ECG collection. 
n After informed consent has been signed but before the administration of the study drug, only serious adverse events (SAEs) should be reported. After initiation 
of the study drug, all adverse events (AEs) and SAEs, regardless of relationship to study drug, will be reported until 30 days after study treatment 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.  
o Refer to Section 8.3.2 for details regarding WHO 8-point ordinal scale. 
p The COVID-19-related symptoms include, but are not limited to, fever, cough, diarrhea, dizziness, rhinorrhea, anosmia, dysgeusia, sore throat, abdominal 
pain, anorexia, and vomiting. Refer to Section 8.3.3 for assessment of disease severity. 
q Local laboratory assessments of clinical chemistry, hematology, coagulation, and urinalysis will be conducted as outlined in Appendix 3. 
r laboratory tests (clinical chemistry, hematology, coagulation, urinalysis, and pregnancy test) performed within 3 days prior to screening visit can be used to 
confirm eligibility. 
s Urine pregnancy test using highly sensitive human chorionic gonadotropin will be performed in all women of childbearing potential at the specified timepoints. 
A confirmation serum pregnancy test must be performed if the urine pregnancy test is positive or equivocal. Serum pregnancy tests may be substituted for 
urine pregnancy tests if the site is not able to perform urine testing. Female patients with negative test results will be eligible to receive the study drug. 
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t Peripheral Blood samples will be collected from patients to explore the association of biomarkers with the efficacy of BGB-DXP593, including but not limited 
to SARS-CoV-2 serology, cytokines and gene expression signatures. Refer to the laboratory manual for instructions regarding sample collection, handling, 
labeling, storage, and shipping of laboratory samples. 
u Saliva samples collected here will also be used for SARS-CoV-2 mutation testing. 
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APPENDIX 3. CLINICAL LABORATORY ASSESSMENTS 
Clinical chemistry 
Hematology 
Coagulation 
Urinalysis 
Alkaline phosphatase 
Alanine aminotransferase 
Aspartate aminotransferase 
Albumin 
Total bilirubin 
Direct bilirubin 
Blood urea nitrogen or urea 
Potassium 
Sodium 
Total calciuma 
Creatinine 
Glucose 
Lactate dehydrogenase 
Total protein 
Magnesium 
C-reactive protein 
Red blood cell count 
Hematocrit 
Hemoglobin 
Platelet count 
White blood cell count 
Lymphocyte count 
Neutrophil count 
Prothrombin time 
Partial thromboplastin 
time or activated 
partial thromboplastin 
time 
International 
normalized ratio 
D-Dimers  
Specific gravity 
pH 
Glucose 
Protein 
Blood 
Ketones 
Bilirubin 
Urobilinogen  
Nitrite 
Leukocyte esterase or 
leukocyte 
Other Tests 
x Follicle-stimulating hormone (FSH) and estradiol test (as needed for female patients who are < 55 years of age 
ZLWK QR VSRQWDQHRXV PHQVHV IRU   PRQWKV WR LGHQWLI\ WKH VWDWXV RI QR FKLOGEHDULQJ SRWHQWLDO 
x Highly sensitive human chorionic gonadotropin pregnancy test (in women of childbearing potential) 
x SARS-CoV-2 RT-qPCR test 
Abbreviations: SARS-CoV-2, Severe Acute Respiratory Syndrome Coronavirus 2; RT-qPCR, reverse 
transcription-quantitative polymerase chain reaction. 
a Total calcium values will be corrected for patients with hypoproteinemia. 
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APPENDIX 4. 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: 
x Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with the inhibition of ovulation 
 Oral, intravaginal, or transdermal 
x 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. 
x Intrauterine device 
x Intrauterine hormone-releasing system 
x Bilateral tubal occlusion 
x 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. 
x 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 patient’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. 
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Definitions of “Women of Childbearing Potential,” “Women of No Childbearing Potential” 
As defined in this protocol, “women of childbearing potential” are female patients who are 
physiologically capable of becoming pregnant. 
Conversely, “women of no childbearing potential” are defined as female patients meeting any of 
the following criteria: 
x Surgically sterile (ie, through bilateral salpingectomy, bilateral oophorectomy, or 
hysterectomy) 
x 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-DXP593-102 
Study Protocol 
Title: 
A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Efficacy and Safety of SARS-CoV-2 Neutralizing 
Antibody BGB-DXP593 in Patients With Mild-to-Moderate COVID-
19 
Date: 
March 4, 2021 
Version: 
2.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
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TABLE OF CONTENTS 
1 
INTRODUCTION 
6 
2 
STUDY OVERVIEW 
6 
3 
STUDY OBJECTIVES 
7 
3.1 
Primary Objectives 
7 
3.2 
Secondary Objectives 
7 
3.3 
Exploratory Objectives 
7 
4 
STUDY ENDPOINTS 
8 
4.1 
Primary Endpoints 
8 
4.2 
Secondary Endpoints 
8 
4.3 
Exploratory Endpoints 
8 
5 
SAMPLE SIZE CONSIDERATIONS 
8 
6 
STATISTICAL METHODS 
9 
6.1 
Analysis Sets 
9 
6.2 
Data Analysis General Considerations 
9 
6.2.1 
Definitions and Computations 
9 
6.2.2 
Conventions 
10 
6.2.3 
Handling of Missing Data 
10 
6.2.4 
Multiplicity Adjustment 
11 
6.2.5 
Data Integrity 
11 
6.3 
Subject Characteristics 
11 
6.3.1 
Patient Disposition 
11 
6.3.2 
Protocol Deviations 
11 
6.3.3 
Demographic and Other Baseline Characteristics 
12 
6.3.4 
Prior and Concomitant Medications 
12 
6.3.5 
Medical History 
12 
6.4 
Efficacy Analysis 
13 
6.4.1 
Primary Endpoint Analyses 
13 
6.4.2 
Secondary Endpoint Analyses 
15 
6.4.3 
Exploratory Endpoint Analyses 
16 
6.4.4 
Subgroup Analyses 
17 
6.5 
Safety Analyses 
17 
6.5.1 
Extent of Exposure 
17 
6.5.2 
Adverse Events 
18 
6.5.3 
Laboratory Values 
19 
6.5.4 
Vital Signs 
20 
6.6 
Pharmacokinetic Analyses 
20 
6.6.1 
Calculation of Serum Pharmacokinetic Parameters 
20 
6.6.2 
Reporting of Pharmacokinetic Concentrations for Descriptive 
Statistics 
21 
6.6.3 
Plots of Pharmacokinetic Concentrations 
21 
6.6.4 
Reporting of PK Parameters for Descriptive Statistics 
21 
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6.6.5 
Software 
22 
6.7 
Immunogenicity Analyses 
22 
6.8 
Other Exploratory Analyses 
23 
7 
INTERIM ANALYSIS 
23 
8 
CHANGES IN THE PLANNED ANALYSIS 
23 
9 
REFERENCES 
23 
10 
APPENDIX 
25 
10.1 
Imputation of partial dates for AEs/Medications/Therapies/Procedures 
25 
 
 
 
 
 
 
 
 
 
 
 
 
 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
ADA 
antidrug antibody 
AE 
adverse event 
AUC 
area under the plasma or serum concentration-time curve 
CI 
confidence interval 
CL/F 
clearance after oral administration 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
MedDRA 
Medical Dictionary for Regulatory Activities 
PK 
pharmacokinetic(s) 
SAP 
Statistical Analysis Plan 
IDMC 
Independent Data Monitoring Committee 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
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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 the protocol BGB-DXP593-102, A 
Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and 
Safety of SARS-CoV-2 Neutralizing Antibody BGB-DXP593 in Patients With Mild –to Moderate 
COVID-19. 
Reference materials for this statistical plan include the protocol BGB-DXP593-102 (original 
version, 2020-08-14, protocol amendment 1.0, 2020-09-03, protocol amendment 2.0, 2020-10-19). 
If the protocol or case report forms are amended or updated then appropriate adjustments to the 
SAP may be made if they are related to the planned analyses. 
The SAP described hereafter is an a priori plan. The SAP will be finalized and approved before 
database lock. Statistical programming may occur as study data accumulate in order to have 
analysis programs ready at the time the study finishes. 
2 
STUDY OVERVIEW 
This is a Phase 2, randomized, double-blind, placebo-controlled study to evaluate the efficacy 
and safety of BGB-DXP593 in patients with mild-to-moderate COVID-19. 
The study will be conducted across approximately 20 to 30 sites internationally. 
After providing written informed consent, completing all the screening assessments, and being 
confirmed as eligible for study participation, patients will be randomized in a 1:1:1:1 ratio to 
receive placebo, BGB-DXP593 5 mg/kg, BGB-DXP593 15 mg/kg, or BGB-DXP593 30 mg/kg. 
Patient randomization will be stratified by country and disease severity (mild versus moderate 
COVID-19). The patients will receive a single intravenous infusion of placebo or BGB-DXP593 
over 30 to 60 minutes. The patients will then be followed to Day 113 (± 7 days) to assess the 
efficacy, safety, PK, and immunogenicity. Nasopharyngeal swabs will be collected for RT-qPCR 
testing of SARS-CoV-2 to assess the change in viral load after study treatment. Approximately 
172 patients will be randomized. 
An Independent Data Monitoring Committee (IDMC) will periodically monitor safety and 
efficacy data. The first safety review is planned after at least 12 patients have been treated and 
followed up for 7 days. 
The study schema is provided in Figure 1. 
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4 
STUDY ENDPOINTS 
4.1 
PRIMARY ENDPOINTS 
• 
Change from baseline to Day 8 in Severe Acute Respiratory Syndrome Coronavirus 2 
(SARS-CoV-2) viral shedding as measured by reverse transcription-quantitative polymerase 
chain reaction (RT-qPCR) in nasopharyngeal swab samples 
4.2 
SECONDARY ENDPOINTS 
• 
Time-weighted average change in SARS-CoV-2 viral shedding as measured by RT-qPCR in 
nasopharyngeal swab samples from baseline to Day 15 
• 
Change in SARS-CoV-2 viral shedding as measured by RT-qPCR in nasopharyngeal swab 
samples from baseline to Day 15 
• 
Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR in 
any tested samples 
• 
Proportion of patients requiring hospitalization due to worsened COVID-19 
• 
Time to resolution of all COVID-19-related symptoms 
• 
All-cause mortality rate at Day 29 
• 
Incidence and severity of treatment-emergent adverse events (TEAEs) and serious adverse 
events (SAEs) 
• 
PK parameters: 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 Day 29 (AUC0-29), AUC from time zero to infinity (AUCinf), time to 
maximum observed concentration (tmax), terminal half-life (t1/2), clearance (CL), and volume 
of distribution (Vz) as appropriate 
• 
Immunogenic responses to BGB-DXP593 evaluated through the detection of antidrug 
antibodies (ADAs) 
4.3 
EXPLORATORY ENDPOINTS 
5 
SAMPLE SIZE CONSIDERATIONS 
The sample size calculation is based on the following assumptions: 
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• 
The primary endpoint “change from baseline to Day 8 in SARS-CoV-2 viral shedding” is 
normally distributed 
• 
One-sided significance level α = 5% 
• 
True maximum treatment effect size of BGB-DXP593 versus placebo is -1.5 log10 copies 
per mL 
• 
Standard deviation is 3.2 log10 copies per mL (Wang et al 2020) 
• 
Prespecified candidate models listed in Section 6.4.1  
Forty-one patients are needed with primary endpoint data per arm to provide at least 82% power 
to detect non-flat dose-response relationship. MCPMod approach is used. In order to ensure 41 
patients per arm with primary endpoint data, at least 43 patients per arm need to be randomized 
to account for potential dropout rate of 5%. 
The calculation has been performed using R software, version 3.6.1. 
6 
STATISTICAL METHODS 
6.1 
ANALYSIS SETS 
• 
The Intent-to-Treat (ITT) Analysis Set includes all randomized patients. Patients will be 
analyzed according to the treatment assigned at randomization. This will be the primary 
analysis set for efficacy analyses. 
• 
The Safety Analysis Set includes all patients who have received the study drug (BGB-
DXP593 or placebo). Patients will be analyzed according to their actual treatment received. 
The Safety Analysis Set will be used for all safety analyses. 
• 
The PK Analysis Set includes all patients who received the study drug (BGB-DXP593) per 
the protocol and for whom any postdose PK data are available. 
• 
The ADA Analysis Set includes all the patients who received the study drug and in whom 
both baseline ADA and at least 1 postbaseline ADA results are available. 
6.2 
DATA ANALYSIS GENERAL CONSIDERATIONS 
6.2.1 Definitions and Computations 
Study day is calculated in reference to the date of randomization.  For assessments conducted on 
or after the date of randomization, study day will be calculated as assessment date – date of 
randomization + 1.  For assessments conducted before the date of randomization, study day is 
calculated as assessment date – date of randomization. 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 10.1. 
Baseline is defined as the last non-missing value collected before the administration of the study 
drug. 
All calculations and analyses will be conducted using SAS version 9.4 or higher. 
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6.2.2 Conventions 
Unless otherwise specified, the following conventions will be applied to all analyses: 
 
• 
1 year = 365.25 days. Number of years is calculated as (days/365.25) rounded up to 1 
decimal place. 
• 
1 month = 30.4375 days. Number of months is calculated as (days/30.4375) rounded up to 1 
decimal place. 
• 
Age will be calculated as the integer part of (date of informed consent – date of birth + 
1)/365.25 
• 
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’.   
• 
Time-to-event or duration of event endpoints will be based on the actual date the test was 
obtained rather than the associated visit date. 
• 
Missing efficacy or safety data will not be imputed unless otherwise specified. 
• 
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. 
• 
For by-visit observed data analyses, percentages will be calculated based on the number of 
patients with non-missing data as the denominator, unless otherwise specified. 
• 
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 where required (e.g. 
shift table). Listings will include scheduled, unscheduled and retest data. 
• 
For continuous endpoints, summary statistics will include n, mean, standard deviation, 
median, Q1, Q3 and range (minimum and maximum). 
6.2.3 Handling of Missing Data 
In general, values for missing data will not be imputed, unless methods for handling missing data 
are specified.  
For MMRM analysis, no imputation will be performed for missing viral shredding. If a patient 
misses a visit, the missing data will not be imputed. The mixed effect model will handle missing 
data based on a likelihood method under the "missing at random” assumption.  
Sensitivity analyses using method of last observation carry forward (LOCF) may be considered to 
assess the potential impact from missing data for MMRM in primary analysis. 
Missing dates or partially missing dates will be imputed conservatively for adverse events and 
prior/concomitant medications/procedures.  Specific rules for handling of missing or partially 
missing dates for adverse events and prior/concomitant medications/procedures are provided in 
Appendix 10.1. 
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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. 
Censoring rules for analyses of time-to-event endpoints are determined as in Table 1. 
Table 1 Censoring Rules for Analyses of Time-to-event Endpoints 
No. 
Situation 
Date of Event or Censoring 
Outcome 
1 
Target event documented 
Date of occurrence of target event 
Event 
2 
Multiple target events documented 
Date of first occurrence of target event 
Event 
3 
No target event or death occurred by the time 
of the End-of-Study Visit or data cut-off, 
whichever comes first 
Date of the End-of-Study Visit or data 
cut-off, whichever comes first 
Censored 
4 
Death and no target event prior to death 
Date of data cutoff 
Censored 
 
 
6.2.4 Multiplicity Adjustment 
The MCPMod procedure allows for simultaneous evaluation of different potential dose response 
patterns, whilst protecting the overall probability of Type I error (one-sided α of 5%). No additional 
multiplicity adjustments will be made in this study. Two-sided 90% confidence interval will be 
used to describe the precision of the rate estimate whenever appropriate. 
6.2.5 Data Integrity 
Before pre-specified interim or final statistical 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 
completed and reviewed up to a pre-specified cutoff date.  Consistency checks and appropriate 
source data verification should be completed. 
6.3 
SUBJECT CHARACTERISTICS 
6.3.1 Patient Disposition 
The number of patients randomized, treated, discontinued from study drug and/or the study will 
be counted. The primary reason for study drug and/or study discontinuation will be summarized 
according to the categories in the eCRF.  
6.3.2 Protocol Deviations 
Important protocol deviation criteria will be established and patients with important protocol 
deviations will be identified and documented before the database lock. 
Important protocol deviations will be summarized for all patients in the Safety Analysis Set and 
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listed by each category. 
6.3.3 Demographic and Other Baseline Characteristics 
Demographic and other baseline characteristics will be summarized using the ITT Analysis Set 
and descriptive statistics. Continuous variables include but are not limited to age, weight for 
determining drug administration, and time from first COVID-19 symptom to date of drug 
administration. Categorical variables include but are not limited to age group, gender, country, 
race, disease severity, serology status, baseline viral load level group in nasopharyngeal swab 
samples, and risk status. 
High risk is defined as patients who meet at least one of the following criteria: 
x Have a body mass index (BMI) ≥ 35 
x Have chronic kidney disease 
x Have diabetes 
x Have immunosuppressive disease 
x Are currently receiving immunosuppressive treatment 
x Are ≥ 65 years of age 
x Are ≥55 years of age AND have 
o cardiovascular disease, OR 
o hypertension, OR 
o chronic obstructive pulmonary disease/other chronic respiratory disease 
6.3.4 Prior and Concomitant Medications 
Prior medications will be defined as medications that stopped before the administration of study 
drug. Concomitant medications will be defined as medications that 1) started before the 
administration of study drug and were continuing at the time of the administration of study drug, 
or 2) started on or after the date of the administration of study drug up to 30 days after dosing. 
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
drug codes and will be further coded to the appropriate Anatomical Therapeutic Chemical code 
indicating therapeutic classification. Prior and concomitant medications will be summarized and 
listed by drug and drug class. A listing of prior and concomitant medications will be provided. 
 
6.3.5 Medical History 
Medical History will be coded using MedDRA (version 23.0 or newer). The number (percentage) 
of subjects reporting a history of any medical condition, as recorded on the eCRF, will be 
summarized by system organ class and preferred term in the safety analysis set. A listing of 
medical history will be provided. 
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6.4 
EFFICACY ANALYSIS 
6.4.1 Primary Endpoint Analyses 
The statistical hypotheses to be tested for the primary endpoint are as follows: 
H0: there is a flat dose response curve comparing change from baseline to Day 8 in SARS-CoV-2 
viral shedding in the placebo and the BGB-DXP593 dose groups 
H1: there is a non-flat dose response curve indicating a benefit of BGB-DXP593 over placebo 
A Mixed Model Repeated Measures (MMRM) analysis will be used to analyze the primary 
endpoint of change from baseline to Day 8 in SARS-CoV-2 viral shedding. This model will 
include treatment, visit, and disease severity at baseline as discrete fixed effects; baseline viral 
shredding as a continuous fixed effect; and interaction between visit and treatment, interaction 
between visit and baseline, and patient as a random effect. The primary treatment comparisons 
will be the contrast between treatments at Day 8. 
The analysis will be carried out and covariate-adjusted fixed effect estimates of average response 
for each treatment and the covariance matrix will be extracted from the fit and used for multiple 
comparison procedures and modelling approaches (MCPMod) analysis.  
The primary analysis uses methodology for dose finding employing both multiple comparison 
procedures and modelling techniques. The MCPMod procedure allows for simultaneous 
evaluation of different potential dose response patterns, whilst protecting the overall probability 
of Type I error (one-sided α of 5%). 
For the hypothesis testing and for the sample size calculation, the basic shape of each of the 
models to be tested must be predefined. The following models will be considered for this 
analysis: linear, Emax, SigEmax and quadratic.  
The model assumptions and resulting graphs were selected to cover both plausible and a diverse 
range of dose response patterns. These are shown in Figure 2. The parameters for each model 
shape are listed in Table 2. 
 
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Figure 2: 
Shape of the Considered Dose Response Patterns for the MCPMod Analysis 
Abbreviation: MCPMod, multiple comparison procedures and modelling approaches 
Table 2: 
Parameter(s) in Each Model 
Model 
Prespecified parameters 
Emax1 
ED50=2.6 
Emax2 
ED50=12.5 
sigEmax 
ED50 = 10, h=4 
Quadratic 
δ = -0.022 
Linear 
No assumption needed 
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If at least one model is statistically significant, then we will reject the null hypothesis of a flat 
dose response relationship over viral shredding change at Day 8, with a multiple contrast test 
controlled for the family-wise type I error rate at one-sided α = 5%. A one-sided p-value that 
corresponds to the most significant model will be calculated. 
Bootstrap method with treatment effect resamples is used to induce dose-response relationship. 
Four candidate models (Emax, sigEmax, Quadratic, and Linear) are fitted and the one with 
lowest gAIC is selected separately for each resample. The target dose(s) can be estimated from 
the average model using bootstrap method by incorporating information on the target treatment 
effect and by accounting for safety. Denote by ܷௗ the upper 0.95 percentile of confidence limit 
of the predicted mean value ݌ௗ at dose ݀ based on the dose-response relationship, where ݀= ݀ଵ 
(placebo), ݀ଶ (5mg/kg), ݀ଷ (15mg/kg), and ݀ସ (30mg/kg). The target dose can be found by 
ܶܦ= ܽݎ݃݉݅݊ௗ∈(ௗభ,ௗೖ]൛݌ௗ< ݌ௗభ+ Δ, Uୢ< ݌ௗభൟ 
where ݇= 1, 2, 3, and 4. The target treatment effect, Δ, is set to -1 logଵ଴copies/ml. 
Comparisons of active doses to placebo (90% confidence intervals [CIs] and p-values) based on 
the mixed effects model will be reported. These are supportive analyses of the primary endpoint 
to supplement the MCPMod analysis, which is the primary analysis. 
6.4.2 Secondary Endpoint Analyses 
Secondary efficacy endpoints will include: 
• 
Time-weighted average change in viral shedding as measured by RT-qPCR in 
nasopharyngeal swab samples from baseline to Day 15 
• 
Change in SARS-CoV-2 viral shedding as measured by RT-qPCR in nasopharyngeal 
swab samples from baseline to Day 15  
• 
Time to negative RT-qPCR in all tested samples with no subsequent positive RT-qPCR 
in any tested samples 
• 
Proportion of patients requiring hospitalization due to worsened COVID-19 
• 
Time to resolution of all COVID-19-related symptoms 
• 
All-cause mortality rate at Day 29 
The time-weighted average change in viral shedding as measured by RT-qPCR in 
nasopharyngeal swab samples from baseline to Day 15 is defined as: 
∑
[0.5 × (ܻ௜+ ܻ௜ାଵ) × (ݐ௜ାଵ−ݐ௜)]
௕ିଵ
௜ୀ௔
ݐ௕−ݐ௔
 
where ܻ௜ is the change from baseline in viral shedding at Visit ݅, ݐ is the time at the specified 
timepoint (the actual study day), ܽ is the baseline assessment at Day 1, and ܾ is the last 
assessment at or prior to Day 15 visit. Analysis of covariance (ANCOVA) model with 
corresponding baseline viral shedding, disease severity at baseline, and treatment as covariates 
will be used. Comparisons of active doses to placebo (90% CIs and p-values) will be provided.  
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The same MMRM analysis for primary endpoint will be used to analyze the change in SARS-
CoV-2 viral shedding from baseline to Day 3 and Day 15. Comparisons of active doses to 
placebo (90% CIs and p-values) will be provided. 
The negative RT-qPCR is defined as the value that is below the lower limit of detection. Kaplan-
Meier method will be used to assess the time to negative RT-qPCR. The corresponding quartiles 
(including the median) will be reported and a two-sided 90% CI of median, if estimable, will be 
constructed with a generalized Brookmeyer and Crowley method for each dosing group. Patients 
who have died prior to experiencing the event of interest will be censored on the day of data 
cutoff. Patients for whom the RT-qPCR value is still positive by the time of end of study visit or 
data cutoff, whichever comes first, will be censored on the last RT-qPCR sample date. 
The number of patients who require hospitalization due to worsened COVID-19 will be counted. 
Corresponding proportion will be derived and a two-sided binomial exact 90% CI of proportion 
will be constructed.  
Time to resolution of all COVID-19-related symptoms is defined as the days from randomization 
to the first day when all symptoms were resolved. Kaplan-Meier method will be used to assess 
the time to resolution of all COVID-19 related symptoms. The corresponding quartiles 
(including the median) will be reported and a two-sided 90% CI of median, if estimable, will be 
constructed with a generalized Brookmeyer and Crowley method for each dosing group. Patients 
who have died prior to experiencing the event of interest will be censored. Their follow-up 
length will be arbitrarily set as (data cutoff date – first patient in date). This approach is to count 
death as the worst possible outcome without possibility of recovery. Patients who have ongoing 
symptoms will be censored at the time of end of study visit or data cutoff, whichever comes first. 
Kaplan-Meier method will be used to assess all-cause mortality rate at Day 29. A two-sided 
90% CI of this rate, if estimable, will be constructed using the Greenwood's formula. Patients 
who do not die will be censored at the time of end of study visit or data cutoff, whichever comes 
first . 
6.4.3 Exploratory Endpoint Analyses 
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as 
-
d. 
 
ll 
6.4.4 Subgroup Analyses 
6.5 
SAFETY ANALYSES 
6.5.1 Extent of Exposure 
Extent of exposure to study drug will be summarized descriptively for the total dose received per 
patient (mg) and relative dose intensity. 
x Total dose (mg): the sum of all actual doses of the study drug 
x Relative dose intensity (RDI) in % is defined as: 
100 ×
Total Dose (mg) 
Planned Dose Level (mg/kg) × Weight 
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where planned dose level equals to 5 mg/kg, 15 mg/kg or 30 mg/kg according to treatment 
arm assignment. For patients in placebo arm, the planned dose level is set to 15 mg/kg. The 
weight is based on a patient’s actual body weight on the day of drug administration. 
The number (percentage) of patients requiring treatment interruption because of AEs will be 
summarized. Reasons for dose interruption will be summarized as well. 
Patient data listings will be provided for all dosing records and for calculated summary statistics. 
6.5.2 Adverse Events  
The AE verbatim descriptions (investigator’s description from the eCRF) will be coded using 
MedDRA. AEs will be coded to MedDRA lowest level term, preferred term, and primary system 
organ class. 
A TEAE is defined as an AE that had an onset date or a worsening in severity from baseline 
(pretreatment) on or after the administration of study drug and up to the 30 days after dosing. 
The incidence of TEAEs will be reported as the number (percentage) of patients with TEAEs by 
system organ class and preferred term. A patient will be counted only once by the highest 
severity grade per NCI-CTCAE Version 5.0 within a system organ class and preferred term, even 
if the patient experienced more than 1 TEAE within a specific system organ class and preferred 
term. The number (percentage) of patients with TEAEs will also be summarized by relationship 
to the study drug. 
Treatment-related TEAEs include those events considered by the investigator to be related to study 
treatment or with missing assessment of the causal relationship. SAEs, deaths, ≥ Grade 3 TEAEs, 
treatment-related TEAEs, and TEAEs that led to treatment discontinuation or treatment 
interruption will be summarized. 
An overview table of patients with at least one TEAE will be presented with the incidence of:  
x 
patients with any TEAE 
x 
patients with any TEAE with grade 3 or higher  
x 
patients with any serious TEAE 
x 
patients with any TEAE leading to death  
x 
patients with any TEAE leading to treatment discontinuation 
x 
patients with any TEAE leading to drug interruption 
x 
patients with any TEAE leading to infusion rate decreased 
 
x 
patients with any treatment-related TEAE 
x 
patients with any treatment-related TEAE with grade 3 or higher 
x 
patients with any treatment-related serious TEAEs 
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x 
patients with any treatment-related TEAE leading to death 
x 
patients with any treatment-related TEAE leading to treatment discontinuation 
x 
patients with any treatment-related TEAE leading to drug interruption 
x 
patients with any treatment-related TEAE leading to infusion rate decreased 
Treatment-related AEs also include those events with missing assessment of the causal 
relationship. 
The incidence of following TEAEs will be reported by SOC and PT, sorted by decreasing order of 
the frequency of the SOC first and then by decreasing order of the frequency of the PT within the 
SOC: 
x patients with any TEAE 
x patients with any serious TEAE 
x patients with any TEAE leading to death  
x patients with any TEAE leading to treatment discontinuation 
x patients with any TEAE leading to drug interruption 
x patients with any treatment-related TEAE 
A patient will be counted only once by the highest grade according to NCI-CTCAE, version 5.0, 
within a SOC and PT, even if the patient experienced more than one TEAE within a specific SOC 
and PT. 
 
The incidence of following TEAEs will be reported by SOC, PT and Worst Grade: 
x patients with any TEAE 
x patients with any treatment-related TEAE 
Subject data listings of all AEs, SAEs, treatment-related AEs, grade 3 or above AEs, AEs that led 
to death and AEs that led to treatment discontinuation, dose interruption will be provided. 
6.5.3 Laboratory Values 
Clinical laboratory (eg, hematology, clinical chemistry, coagulation, and urinalysis) values will 
be evaluated for each laboratory parameter as appropriate. Reference (normal) ranges for 
laboratory parameters will be provided.  
Laboratory parameters are graded by NCI-CTCAE Version 5.0 or higher and will be summarized 
through shift tables from baseline to the worst postbaseline grade. Grade 3 or 4 laboratory toxicity 
will be summarized, and parameters with NCI-CTCAE grading in both high and low directions 
will be summarized separately. 
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6.5.4 Vital Signs 
Descriptive statistics for vital sign parameters (systolic and diastolic blood pressure, SpO2, 
respiratory rate, pulse rate, and body temperature) and changes from baseline will be presented 
by visit for all visits. Vital signs will be listed by patient and visit.  
6.6 
PHARMACOKINETIC ANALYSES 
The following analysis plan provides the framework for the summarization of the PK data from 
study BGB-DXP593-102. The objective is to assess BGB-DXP593 PK and characterize PK 
parameters following a single IV dose. The PK analyses will be based on the BGB-DXP593 PK 
analysis set. 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. 
 
Parameter 
(Units) 
Definition 
Method of Determination 
AUC0-29 
(μg·hr/mL) 
Area under the serum concentration 
versus time curve from 0 to Day 29 
Calculated using the linear up/log down variant 
of the trapezoidal rule 
AUCinf 
(μg·hr/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 
AUCt 
(μg·hr/mL) 
AUC from time zero to time t 
Calculated using the linear up/log down variant 
of the trapezoidal rule 
Cmax (μg/mL) 
Maximum observed drug concentration 
during a dosing interval 
Observed value 
tmax (h) 
Time to reach Cmax 
Actual elapsed time for observed Cmax in each 
period. 
t1/2 (hr) 
half-life 
ln(2)/λz, where λz 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/λz, where λz is the first-order 
rate constant of drug associated with the 
terminal portion of the curve 
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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.  
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 "missing" 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.  
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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 
μg/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. 
6.7 
IMMUNOGENICITY ANALYSES 
The scope of reporting conventions and calculation methodologies used for characterizing 
clinical immunogenicity depends on the incidence and kinetics of anti-drug antibodies detected 
(ADA). 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. 
 
The immunogenicity results will be listed and summarized using descriptive statistics by the 
number and percentage of subjects who develop detectable ADAs.  If data permit, 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. 
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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: 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: patients with positive nab. 
6.8 
OTHER EXPLORATORY ANALYSES 
7 
INTERIM ANALYSIS 
A primary analysis of efficacy and safety is planned after all patients have finished Day 8 visit or 
discontinued the study earlier. Pharmacokinetic, immunogenicity and exploratory biomarkers will 
not be a part of the primary analysis.  
8 
CHANGES IN THE PLANNED ANALYSIS 
Not applicable.  
9 
REFERENCES 
Brookmeyer R, Crowley J. A Confidence interval for the median survival time. Biometrics. 1982; 
38: 29-41. 
Clopper, C. and Pearson, ES. The use of confidence or fiducial limits illustrated in the case of the 
binomial, Biometrika 1934;26: 404-413.  
Collett D. Modelling survival data in medical research. New York: Chapman & Hall; 1994.  
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. 
Kaplan E, Meier P.  Nonparametric estimation from incomplete observations.  J Am Stat Assoc. 
1958;53:457-81. 
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Buckland, S. T., Burnham, K. P. and Augustin, N. H. (1997). Model selection an integral part of 
inference, Biometrics, 53, 603–618 
Yeming Wang et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, 
placebo-controlled, multicentre trial. Lancet. 2020 May 16;395(10236):1569-1578. 
Pinheiro, J. C., Bornkamp, B., and Bretz, F. (2006).  Design and analysis of dose finding 
studiescombining multiple comparisons and modeling procedures,Journal of Biopharmaceutical 
Statis-tics,16, 639–656 
Bornkamp B., Pinheiro J. C., and Bretz, F. (2009).  MCPMod:  An R Package for the Design 
andAnalysis of Dose-Finding Studies,Journal of Statistical Software,29(7), 1–23  
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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10 APPENDIX 
10.1 IMPUTATION OF PARTIAL DATES FOR AES/MEDICATIONS/THERAPIES/PROCEDURES 
Imputation for AEs with missing or partial dates 
If AE start (onset) date/end are 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, the set to 
treatment start date 
• 
If day is missing and month and year ≠ month and year of treatment start date, the 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).  
Imputation for medications/therapies/procedures with missing or partial dates 
When the start date or end date of a medication/therapy/procedure is partially missing, the date 
will be imputed to determine whether the medication/therapy/procedure is prior or concomitant. 
The following rules will be applied to impute partial dates for medication/therapy/procedure: 
If start date of a medication/therapy/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/therapy/procedure 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 
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• 
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/therapy/procedure is missing, or the 
start date or end date is completely missing, do not impute. 
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