Clinical trial NCT04669262
Conditions: Healthy
Sponsor: BeiGene
Start date: 2020-12-09; Completion date: 2021-05-21
Enrollment: 25 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
The primary objective of this study is to investigate the safety and tolerability of BGB-DXP604 alone and in combination with BGB-DXP593 in healthy participants

Detailed description:

Arms: arm 1: Part 1A: Single low dose of BGB-DXP604 or placebo; Part 1B: Single high dose of BGB-DXP604 or placebo arm 2: Single dose of BGB-DXP593 followed by a single dose of BGB-DXP604 or placebo
Interventions: intervention 1: BGB-DXP604 intervention 2: BGB-DXP593 intervention 3: Placebo intervention 4: Placebo
Intervention descriptions: intervention 1: Administered as intravenous (IV) infusion over 30 to 60 minutes intervention 2: Administered as intravenous (IV) infusion over 30 to 60 minutes intervention 3: Placebo to match BGB-DXP593 intervention 4: Placebo to match BGB-DXP604

Protocol documents:
Prot_000.pdf: 
BGB-DXP604-101
BeiGene
Original Protocol Version 0.0
23 November 2020
CONFIDENTIAL
Page 1
CLINICAL STUDY PROTOCOL
Protocol Title: 
A Phase 1, Randomized, Double-Blind, Placebo-Controlled
Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, and Immunogenicity of BGB-DXP604
Alone and in Combination With BGB-DXP593 in Healthy 
Subjects
Protocol Identifier:
BGB-DXP604-101
Phase:
1
Investigational Product:
BGB-DXP604 and BGB-DXP593 
Proposed Indication:
Not Applicable
Sponsor:
BeiGene, Ltd. 
c/o BeiGene AUS Pty Ltd.
1C/528 Compton Road Stretton
Queensland 4116, Australia
Sponsor Medical Monitor
Original Protocol Version 0.0:
23 November 2020
Confidentiality Statement
This Document Is Not for Distribution – Do Not Copy
This document contains confidential information and is the proprietary property of BeiGene, Ltd., and its 
subsidiaries. This document is for use by individuals and their designated representatives for their 
confidential review, consideration, and/or participation in investigational trial(s). This document may not 
be copied or distributed for review by any unauthorized individuals without the prior written authorization 
of BeiGene, Ltd., or one of its subsidiaries. Your acceptance of this document constitutes agreement that 
you will not disclose the information contained herein to others without the prior written authorization 
from BeiGene, Ltd., or one of its subsidiaries.
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INVESTIGATOR SIGNATURE PAGE
Protocol Title:
A Phase 1, Randomized, Double-Blind, Placebo-Controlled 
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, 
and Immunogenicity of BGB-DXP604 Alone and in 
Combination With BGB-DXP593 in Healthy Subjects 
Protocol Identifier:
BGB-DXP604-101
This protocol is a confidential communication of BeiGene, Ltd., and its subsidiaries. I confirm 
that I have read this protocol, I understand it, and I will work according to this protocol and the 
terms of the clinical study agreement governing the study. I will also work consistently with the 
ethical principles that have their origin in the Declaration of Helsinki and that are consistent with 
good clinical practices and the applicable laws and regulations. Acceptance of this document 
constitutes my agreement that no unpublished information contained herein will be published or 
disclosed without prior written approval from BeiGene, Ltd., or one of its subsidiaries.
Instructions for Investigator: Please SIGN and DATE this signature page prior to 
implementation of this sponsor-approved protocol. PRINT your name, title, and the name and 
address of the center in which the study will be conducted. 
I have read this protocol in its entirety and agree to conduct the study accordingly:
Signature of Investigator:
Date:
Printed Name:
Investigator Title:
Name/Address of Center:
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TABLE OF CONTENTS
FINAL PROTOCOL APPROVAL SHEET ....................................................................................2 
INVESTIGATOR SIGNATURE PAGE.........................................................................................3 
TABLE OF CONTENTS.................................................................................................................4 
LIST OF TABLES.........................................................................................................................10 
LIST OF FIGURE..........................................................................................................................10 
SYNOPSIS ....................................................................................................................................11 
LIST OF ABBREVIATIONS AND TERMS................................................................................15 
1. 
INTRODUCTION AND RATIONALES ..................................................................17 
1.1. 
Introduction.................................................................................................................17 
1.2. 
BGB-DXP604 as a SARS-CoV-2 Neutralizing Monoclonal Antibody.....................17 
1.2.1. 
Summary of Relevant Nonclinical Data With BGB-DXP604 ...................................18 
1.2.1.1. 
Pharmacology .............................................................................................................18 
1.2.1.2. 
Toxicology..................................................................................................................19 
1.2.2. 
Summary of Relevant Clinical Experience With BGB-DXP604...............................19 
1.3. 
BGB-DXP593 as a SARS-CoV-2 Neutralizing Monoclonal Antibody.....................19 
1.3.1. 
Summary of Relevant Nonclinical Data With BGB-DXP593 ...................................19 
1.3.1.1. 
Pharmacology .............................................................................................................19 
1.3.1.2. 
Toxicology..................................................................................................................20 
1.3.2. 
Summary of Relevant Clinical Experience With BGB-DXP593...............................21 
1.4. 
Study Rationale...........................................................................................................21 
1.4.1. 
Rationale for Matching Placebo as the Comparator...................................................21 
1.4.2. 
Rationale for Selection of BGB-DXP604 Dose .........................................................21 
1.4.2.1. 
Allometric Scaling for Human Pharmacokinetics Projection.....................................21 
1.4.2.2. 
Recommendation of the Starting Dose of BGB-DXP604 in Healthy Subjects..........23 
1.4.3. 
Rationale for the Selection of BGB-DXP593 Dose ...................................................23 
1.4.4. 
Rationale for the Combination of BGB-DXP604 and BGB-DXP593 .......................23 
1.4.5. 
Rationale for Pharmacokinetic Sampling ...................................................................24 
1.5. 
Benefit-Risk Assessment............................................................................................24 
1.6. 
Study Conduct ............................................................................................................25 
2. 
STUDY OBJECTIVES AND STUDY ENDPOINTS ...............................................26 
2.1. 
Study Objectives.........................................................................................................26 
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2.1.1. 
Primary Objective.......................................................................................................26 
2.1.2. 
Secondary Objectives .................................................................................................26 
2.2. 
Study Endpoints..........................................................................................................26 
2.2.1. 
Primary Endpoint........................................................................................................26 
2.2.2. 
Secondary Endpoints ..................................................................................................26 
3. 
STUDY DESIGN .......................................................................................................27 
3.1. 
Summary of Study Design..........................................................................................27 
3.2. 
Details of Dose Escalation (Part 1).............................................................................28 
3.2.1. 
Starting Dose and Dose Escalation Approach (Part 1)...............................................28 
3.2.2. 
Rules for Dose Escalation (Part 1)..............................................................................29 
3.3. 
Initiation of Combination Cohort (Part 2) ..................................................................29 
3.4. 
Criteria for Pausing Drug Administration and New Enrollment................................29 
4. 
SELECTION OF STUDY POPULATION................................................................31 
4.1. 
Inclusion Criteria ........................................................................................................31 
4.2. 
Exclusion Criteria.......................................................................................................31 
5. 
STUDY TREATMENT..............................................................................................34 
5.1. 
Formulation, Packaging, and Handling ......................................................................34 
5.1.1. 
BGB-DXP604.............................................................................................................34 
5.1.2. 
BGB-DXP593.............................................................................................................34 
5.1.3. 
Placebo........................................................................................................................35 
5.2. 
Dosage, Administration, and Compliance..................................................................35 
5.3. 
Measures to Minimize Bias: Randomization and Blinding........................................36 
5.4. 
Incorrect Administration.............................................................................................37 
5.5. 
Dose Interruption or Modification..............................................................................37 
6. 
PRIOR AND CONCOMITANT THERAPY.............................................................38 
6.1. 
Prior Therapy..............................................................................................................38 
6.2. 
Concomitant Therapy .................................................................................................38 
6.3. 
Potential Interactions Between BGB-DXP604 or BGB-DXP593 and 
Concomitant Medications...........................................................................................38 
7. 
STUDY PERIODS, VISITS, OR PROCEDURES ....................................................39 
7.1. 
Screening Period.........................................................................................................39 
7.1.1. 
Informed Consent .......................................................................................................39 
7.2. 
Enrollment ..................................................................................................................39 
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7.2.1. 
Confirmation of Eligibility .........................................................................................39 
7.2.2. 
Subject Numbering .....................................................................................................39 
7.3. 
Check-in (Day -1).......................................................................................................39 
7.4. 
Randomization............................................................................................................40 
7.5. 
Treatment (Day 1).......................................................................................................40 
7.6. 
Follow-up Period ........................................................................................................40 
7.6.1. 
Check-out (Day 3) ......................................................................................................40 
7.6.2. 
End-of-Study Visit......................................................................................................40 
7.6.3. 
Safety Follow-up Visit for Premature Study Discontinuation....................................40 
7.6.4. 
Lost to Follow-up .......................................................................................................40 
7.7. 
Premature Discontinuation From Study Treatment or From the Study......................41 
7.7.1. 
Subject Premature Discontinuation From the Study Treatment .................................41 
7.7.2. 
Subject Premature Discontinuation From the Study ..................................................41 
7.8. 
End of Study ...............................................................................................................41 
8. 
STUDY ASSESSMENTS ..........................................................................................43 
8.1. 
Screening Assessments...............................................................................................43 
8.1.1. 
Demographic Data, Medical History, and Prior Medications ....................................43 
8.2. 
Safety Assessments.....................................................................................................43 
8.2.1. 
Vital Signs ..................................................................................................................43 
8.2.2. 
Physical Examinations................................................................................................43 
8.2.3. 
Laboratory Safety Tests..............................................................................................44 
8.2.4. 
Electrocardiograms.....................................................................................................44 
8.2.5. 
Cardiac Telemetry ......................................................................................................44 
8.2.6. 
Adverse Events ...........................................................................................................44 
8.2.7. 
Serology......................................................................................................................45 
8.2.8. 
Virology......................................................................................................................45 
8.3. 
Pharmacokinetic Assessment and Antidrug Antibody Testing ..................................45 
8.4. 
Visit Windows ............................................................................................................45 
8.5. 
Unscheduled Visits .....................................................................................................46 
9. 
SAFETY MONITORING AND REPORTING .........................................................47 
9.1. 
Risks Associated With BGB-DXP604 .......................................................................47 
9.2. 
Risks Associated With BGB-DXP593 .......................................................................47 
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9.3. 
General Plan to Manage Safety Concerns ..................................................................47 
9.3.1. 
Eligibility Criteria.......................................................................................................47 
9.3.2. 
Safety Monitoring Plan...............................................................................................47 
9.4. 
Adverse Events ...........................................................................................................48 
9.4.1. 
Definitions and Reporting...........................................................................................48 
9.4.2. 
Assessment of Severity...............................................................................................48 
9.4.3. 
Assessment of Causality.............................................................................................49 
9.4.4. 
Following Adverse Events and Serious Adverse Events............................................50 
9.4.5. 
Laboratory Test Abnormalities...................................................................................50 
9.5. 
Definition of a Serious Adverse Event .......................................................................51 
9.6. 
Suspected Unexpected Serious Adverse Reaction .....................................................51 
9.7. 
Timing, Frequency, and Method of Capturing Adverse Events and Serious 
Adverse Events ...........................................................................................................52 
9.7.1. 
Adverse Event Reporting Period ................................................................................52 
9.7.2. 
Reporting of Serious Adverse Events.........................................................................52 
9.7.2.1. 
Prompt Reporting of Serious Adverse Events............................................................52 
9.7.2.2. 
Completion and Transmission of the Serious Adverse Event Report ........................52 
9.7.2.3. 
Regulatory Reporting Requirements for Serious Adverse Events .............................53 
9.7.3. 
Eliciting Adverse Events ............................................................................................53 
9.7.4. 
Death...........................................................................................................................53 
9.7.5. 
Recording Pregnancies ...............................................................................................53 
9.7.6. 
Expedited Reporting to Health Authorities, Investigators, Institutional 
Review Boards, and Independent Ethics Committees................................................54 
9.7.7. 
Reporting Infusion-Related Reactions........................................................................54 
9.8. 
Management of Infusion-Related Reactions and Severe Hypersensitivity 
Reactions.....................................................................................................................54 
9.8.1. 
Managing Infusion-Related Reactions .......................................................................54 
9.8.2. 
Severe Hypersensitivity Reactions .............................................................................56 
10.
STATISTICAL METHODS AND SAMPLE SIZE DETERMINATION.................57 
10.1. 
Statistical Analysis......................................................................................................57 
10.1.1. 
Randomization Method ..............................................................................................57 
10.1.2. 
Analysis Sets...............................................................................................................57 
10.1.3. 
Subject Disposition.....................................................................................................57 
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10.1.4. 
Demographics and Other Baseline Characteristics.....................................................57 
10.1.5. 
Prior and Concomitant Therapy..................................................................................57 
10.2. 
Efficacy Analyses .......................................................................................................58 
10.3. 
Safety Analyses ..........................................................................................................58 
10.3.1. 
Extent of Exposure .....................................................................................................58 
10.3.2. 
Adverse Events ...........................................................................................................58 
10.3.3. 
Laboratory Analyses...................................................................................................58 
10.3.4. 
Vital Signs ..................................................................................................................59 
10.3.5. 
Electrocardiogram.......................................................................................................59 
10.4. 
Pharmacokinetic Analyses..........................................................................................59 
10.5. 
Immunogenicity Analyses ..........................................................................................59 
10.6. 
Sample Size Consideration.........................................................................................59 
10.7. 
Interim Analysis..........................................................................................................59 
11. 
STUDY COMMITTEE ..............................................................................................60 
11.1. 
Safety Monitoring Committee ....................................................................................60 
12. 
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS ...............................................................................................61 
12.1. 
Access to Information for Monitoring........................................................................61 
12.2. 
Access to Information for Auditing or Inspections ....................................................61 
13. 
QUALITY ASSURANCE AND QUALITY CONTROL .........................................62 
13.1. 
Regulatory Authority Approval..................................................................................62 
13.2. 
Quality Assurance.......................................................................................................62 
13.3. 
Study Site Inspections.................................................................................................62 
13.4. 
Drug Accountability ...................................................................................................62 
14. 
ETHICS/PROTECTION OF HUMAN SUBJECTS..................................................64 
14.1. 
Ethical Standard..........................................................................................................64 
14.2. 
Institutional Review Board/Independent Ethics Committee ......................................64 
14.2.1. 
Protocol Amendments ................................................................................................64 
14.3. 
Informed Consent .......................................................................................................65 
14.4. 
Subject and Data Confidentiality................................................................................65 
14.5. 
Financial Disclosure ...................................................................................................66 
15. 
DATA HANDLING AND RECORD KEEPING ......................................................67 
15.1. 
Data Collection and Management Responsibilities....................................................67 
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15.1.1. 
Data Entry in the Electronic Case Report Form .........................................................67 
15.1.2. 
Data Collection ...........................................................................................................67 
15.1.3. 
Data Management/Coding..........................................................................................67 
15.2. 
Study Records Retention ............................................................................................68 
15.3. 
Protocol Deviations ....................................................................................................69 
15.4. 
Study Report and Publications....................................................................................69 
15.5. 
Study and Study Center Closure.................................................................................70 
15.6. 
Information Disclosure and Inventions ......................................................................70 
16. 
REFERENCES ...........................................................................................................72 
APPENDIX 1. SCHEDULE OF ASSESSMENTS ....................................................................74 
APPENDIX 2. SCHEDULE OF ASSESSMENT FOR DAY 1 .................................................78 
APPENDIX 2A. SCHEDULE OF ASSESSMENTS FOR DAY 1 (Part 1)...............................79 
APPENDIX 2B. SCHEDULE OF ASSESSMENTS FOR DAY 1 (Part 2) ...............................80 
APPENDIX 3. PHARMACOKINETIC AND ANTIDRUG ANTIBODY BLOOD 
SAMPLING)...............................................................................................................81 
APPENDIX 3A. PHARMACOKINETIC AND ANTIDRUG ANTIBODY BLOOD 
SAMPLING (Part 1)...................................................................................................82 
APPENDIX 3B. PHARMACOKINETIC AND ANTIDRUG ANTIBODY BLOOD 
SAMPLING (Part 2)...................................................................................................83 
APPENDIX 4. CLINICAL LABORATORY ASSESSMENTS ................................................84 
APPENDIX 5. CONTRACEPTION GUIDELINES AND DEFINITIONS OF 
“WOMEN OF CHILDBEARING POTENTIAL”, “NO CHILDBEARING 
POTENTIAL”.............................................................................................................85 
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LIST OF TABLES
Table 1: 
BGB-DXP604 Population PK Parameter Estimates in Cynomolgus Monkeys 
and Projected PK Parameters in Humans ...................................................................22 
Table 2: 
Projected Safety Margins at Proposed Doses in Humans...........................................23 
Table 3: 
Planned Cohorts and Number of Subjects in Each Cohort.........................................28 
Table 4: 
Planned Dose Level(s) for Study Drug(s) in Each Cohort .........................................35 
Table 5: 
Timeframe and Documentation Methods for Reporting Serious Adverse
Events to the Sponsor or Designee .............................................................................52 
Table 6: 
Treatment Modifications for Symptoms of Infusion-Related Reactions Due 
to Study Drug(s) .........................................................................................................55 
LIST OF FIGURE
Figure 1: 
Simulated BGB-DXP604 Serum and Lung (Assuming 1% Biodistribution) 
Concentration-Time Profiles in Humans....................................................................22 
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SYNOPSIS
Name of Sponsor/Company: BeiGene, Ltd.
Investigational Product: BGB-DXP604 and BGB-DXP593
Title of Study: A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the 
Safety, Tolerability, Pharmacokinetics, and Immunogenicity of BGB-DXP604 Alone and in 
Combination With BGB-DXP593 in Healthy Subjects
Protocol Identifier: BGB-DXP604-101
Phase of Development: 1
Number of Subjects: ≤30 healthy subjects
Study Centers: 1 to 2 centers in Australia 
Study Objectives 
Primary Objective
x
To investigate the safety and tolerability of BGB-DXP604 alone and in combination with 
BGB-DXP593 in healthy subjects
Secondary Objectives
x
To characterize the pharmacokinetic (PK) profile of BGB-DXP604 when given alone in 
healthy subjects
x
To characterize the PK profiles of BGB-DXP604 and BGB-DXP593 when given in 
combination in healthy subjects
x
To evaluate the potential immunogenicity of BGB-DXP604 when given alone in healthy 
subjects
x
To evaluate the potential immunogenicity of BGB-DXP604 and BGB-DXP593 when given in 
combination in healthy subjects
Study Endpoints
Primary Endpoint
x
Incidence and severity of treatment-emergent adverse events (TEAEs) and treatment-emergent 
serious adverse events (SAEs) 
Secondary Endpoints
x
Changes from baseline in vital signs and 12-lead electrocardiogram (ECG) parameters
x
Incidence and magnitude of clinical laboratory abnormalities
x
Characterize PK concentration-time profile and PK parameters of BGB-DXP604 and
BGB-DXP593: maximum observed concentration (Cmax), area under the concentration-time 
curve (AUC) from time zero to the time of the last quantifiable concentration (AUCt), AUC 
from time zero to infinity (AUCinf), AUC from time zero to Day 29 (AUC0-29), time to 
maximum observed concentration (tmax), terminal half-life (t1/2), clearance (CL), and volume of 
distribution (Vz) as appropriate
x
Clinical immunogenicity of BGB-DXP604 and BGB-DXP593 evaluated through the detection 
of antidrug antibodies (ADAs) over time
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Study Design 
This is a Phase 1, randomized, double-blind, placebo-controlled study to investigate the safety, 
tolerability, PK, and immunogenicity of BGB-DXP604 alone and in combination with BGB-DXP593 
in healthy subjects. 
After providing written informed consent, subjects will complete all screening assessments. After being 
confirmed as eligible, subjects will be sequentially enrolled for 2 cohorts of different dose levels
(referred to as Part 1). Two dose levels are planned for eligible subjects to receive a single intravenous 
dose of study drug (ie, BGB-DXP604 or placebo) at 10 mg/kg or 30 mg/kg, respectively. 
Enrollment will begin at the 10 mg/kg dose level. Each dose level of study drug evaluated may be 
referred to as a cohort or dose level.
In Part 2, the combination of BGB-DXP604 and BGB-DXP593 will be tested in eligible subjects.
Subjects enrolled in Cohort 2A will either receive the combination of BGB-DXP604 and 
BGB-DXP593 or placebo (ie, the normal saline with volume equal to BGB-DXP604 or BGB-DXP593
via separate intravenous infusions). The doses of BGB-DXP604 and BGB-DXP593 will be 
recommended by SMC and not exceed 30 mg/kg for each study drug.
In this study, after the last subject in the current cohort has received the study drug and has been 
followed up for ≥5 days, the Safety Monitoring Committee (SMC) will review the available safety and 
laboratory data. The next cohort will be initiated after the SMC review. The dose level of 
BGB-DXP604 in Cohort 1B and Cohort 2A may be adjusted based on SMC recommendation.
In each cohort, eligible subjects will be randomized at a 3:1 ratio (6 active: 2 control) to the active arm 
for receiving the study drug(s) (ie, BGB-DXP604 alone or the combination of BGB-DXP604 and 
BGB-DXP593) or to the control arm for receiving placebo, respectively. For safety reasons, the 
sentinel dosing will be adopted for each cohort. In other words, 2 eligible subjects will be randomized 
at a 1:1 ratio (1 active: 1 control) to receive the study drug(s) or placebo on Day 1; the remaining 
subjects will be randomized at a 5:1 ratio (5 active: 1 control) to receive the study drug(s) or placebo 
≥48 hours later, provided that satisfactory safety and tolerability has been demonstrated for the first 
2 subjects randomized and dosed in the current cohort.
Part
Cohort
Number of Subjects
Active Arm
Control Arm 
(Normal Saline)
1: BGB-DXP604 alone
1A: 10 mg/kg
6
2
1B: 30 mg/kg a
6
2
2: BGB-DXP604
+ BGB-DXP593
2A: 30 mg/kg b BGB-DXP604
+ 30 mg/kg b BGB-DXP593
6
2
Abbreviation: SMC, Safety Monitoring Committee.
a
The dose level of BGB-DXP604 in Cohort 1B may be adjusted based on SMC recommendation.
b
The doses of BGB-DXP604 and BGB-DXP593 in Cohort 2A will be recommended by SMC and not exceed 
30 mg/kg for each study drug.
In this study, subjects are expected to be available for follow-up visits until Day 113 of the study. 
Subjects will be replaced if they cannot complete the infusion or they do not receive any study drug 
after randomization. Subjects may be replaced if they discontinue from the study before Day 29.
Administration of study drug(s) and enrollment of new subjects will be paused for the current cohort if 
any of the following events occurs: 
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One or more ≥Grade 4 TEAEs or treatment-emergent SAEs related to study drug(s) as 
assessed by the investigator in any subject or
x
One or more Grade 3 TEAEs related to study drug(s) as assessed by the investigator in 
≥2 subjects in the same cohort.
The SMC will review the safety and laboratory data of each cohort. The SMC may recommend keeping 
the current enrollment plan, opening a repeated cohort at the same dose of study drug(s), de-escalating
to a lower dose of study drug(s), or terminating the study. For the repeated cohort at the same dose
level and the cohort at the lower dose level, the number of subjects and randomization ratio will be the
same as planned for each cohort.
If the TEAE(s) previously observed at the same dose level occurs again in a repeated cohort at the 
same dose level, no higher dose level will be tested in Part 1. If the same situation occurs in the 
repeated cohort in Part 2, no combination of higher doses will be tested.
Study Assessments:
Subjects will be monitored throughout the study for safety, tolerability, PK, and immunogenicity of 
BGB-DXP604 and BGB-DXP593.
Assessments of safety will include adverse events (AEs), SAEs, clinical laboratory tests, physical 
examinations, vital signs, and ECGs. AEs will be graded for severity per the current version of the 
National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE
v5.0). The SMC will periodically monitor safety data. 
PK and ADA sampling will be collected at specific intervals from Day 1 to Day 113.
Key Eligibility Criteria
Subjects to be included in this study will be adults from 18 to 60 years of age at the time of informed 
consent and in good general health. 
Test Product, Dose, and Mode of Administration
In Cohort 1A and Cohort 1B: 10mg/kg and 30 mg/kg BGB-DXP604 will be administered 
intravenously for 30 to 60 minutes, respectively.
In Cohort 2A: 30 mg/kg BGB-DXP593 will be administered intravenously first, followed by the 
intravenous infusion of BGB-DXP604 at 30 mg/kg. Each study drug will be administered 
intravenously for 30 to 60 minutes. BGB-DXP604 infusion will be given ≥30 minutes after the
completion of the BGB-DXP593 infusion.
Reference Therapy, Dose, and Mode of Administration
Normal saline (ie, solution of 0.9% sodium chloride) will be administered intravenously for 30 to 
60 minutes.
Statistical Methods
The focus of this Phase 1 study is to evaluate the safety, tolerability, PK, and immunogenicity of 
BGB-DXP604 alone and in combination with BGB-DXP593 in healthy subjects. No formal statistical 
hypotheses will be tested.
Analysis Sets:
The Safety Analysis Set will include all subjects who received either study drug.
The PK Analysis Set will include all subjects who received either study drug and had any measurable 
concentration of study drug(s).
The ADA Analysis Set will include all subjects who received either study drug and for whom both 
baseline ADA and ≥1 postbaseline ADA results are available.
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Safety Analyses:
AEs, ECGs, vital signs, and laboratory data will be reviewed and summarized on an ongoing basis 
during the study to evaluate the safety of subjects. Descriptive statistics will be used to analyze all 
safety data.
A TEAE is defined as an AE that had an onset date or a worsening in severity from baseline on or after 
the administration of study drug(s) and ≤30 days after the administration of study drug(s). Only those 
AEs that were treatment emergent will be included in the summary tables. The incidence of TEAEs 
will be reported as the number (percentage) of subjects with TEAEs by System Organ Class and 
Preferred Term. The treatment-emergent SAEs and treatment-related TEAEs will also be summarized. 
All AEs, treatment emergent or otherwise, will be presented in subject data listings.
Changes from baseline for the ECG parameters and vital signs will be summarized by visit and 
treatment group.
Abnormal laboratory values will be flagged and identified as those outside (above or below) the normal 
range. Laboratory parameters and their changes from baseline will be summarized by visit and 
treatment group.
Pharmacokinetic Analyses:
Noncompartmental analyses will be carried out for BGB-DXP604 and BGB-DXP593 serum 
concentrations. 
Parameters, such as Cmax, tmax, t1/2, AUCt, AUCinf, AUC0-29, CL, and Vz (as appropriate for data 
collected), may be derived and summarized using 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 treatment group. Additional PK 
analyses may be conducted as appropriate.
Immunogenicity Analyses:
The immunogenicity results for BGB-DXP604 and BGB-DXP593 will be summarized using 
descriptive statistics by the number and percentage of subjects who develop detectable ADAs. The 
incidence of positive and neutralizing ADAs will be reported for evaluable subjects. The effect of 
immunogenicity on PK and safety may be evaluated if data allow.
Sample Size Consideration:
A sample size of 8 subjects for each cohort (6 active and 2 control) totaling ≤30 subjects (including 
possible replacement) is not based on any statistical considerations. The choice of sample size is based 
on clinical considerations to provide safety and tolerability information as well as pharmacological 
considerations with the need to minimize exposure of healthy subjects in each cohort. No formal 
inferential statistics will be applied to the safety or PK data.
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LIST OF ABBREVIATIONS AND TERMS
Abbreviation
Definition
ACE2
angiotensin-converting enzyme 2
ADA
antidrug antibody
ADE
antibody dependent enhancement
AE
adverse event
AUC
area under the concentration-time curve
BGB-DXP593
code name for monoclonal antibody BGB-DXP593, also named DXP593, 
BD-368-2, and WBP2281
BGB-DXP604
code name for monoclonal antibody BGB-DXP604, also named DXP-604,
BD-604, and WBP2316
CL
clearance
Cmax
maximum observed concentration
COVID-19
coronavirus disease 2019
ECG
electrocardiogram
eCRF
electronic case report form
EOS
End-of-Study
Fab
antigen-binding fragment
FIH
first-in-human
GCP
Good Clinical Practice
ICF
informed consent form
IEC
Independent Ethics Committee
IgG
Immunoglobulin G, such as IgG1
IRB
Institutional Review Board
IRT
Interactive Response Technology
mAb
monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
NCI-CTCAE
National Cancer Institute-Common Terminology Criteria for Adverse Events
PMBC
peripheral blood mononuclear cell
PK
pharmacokinetic(s)
PT
Preferred Term
RBD
receptor-binding domain
SAE
serious adverse event
SARS-CoV-2
severe acute respiratory syndrome coronavirus 2
SMC
Safety Monitoring Committee
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Abbreviation
Definition
SOC
System Organ Class
TEAE
treatment-emergent adverse event
t1/2
terminal half-life
tmax
time to maximum observed concentration 
VZ
volume of distribution
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1.
INTRODUCTION AND RATIONALES
1.1.
Introduction
Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by a new strain of 
coronavirus: severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Zhou et al 2020).
As of November 19, 2020, over 55 million confirmed cases of COVID-19 infection worldwide 
have been reported to the World Health Organization (WHO), including ≥1 million confirmed 
deaths. COVID-19 is threatening the global public health, and the ongoing spread of COVID-19,
which has resulted in a worldwide pandemic, demands effective interventions against 
SARS-CoV-2 infections (WHO 2020).
Currently, several strategies are used in the clinic settings or are under development, such as 
viral-targeting therapeutics and host-targeting agents (eg, anti-interleukin 6 antibodies and 
glucocorticoids) for the treatment of COVID-19. Recently, the United States (US) Food and 
Drug Administration (FDA) has granted the approval of remdesivir (Veklury®) for the treatment 
of COVID-19 in adults and pediatric patients (≥12 years of age) weighing ≥40 kg who require
hospitalization. However, there is no vaccine and no other prescription drug regimens that have
demonstrated significant efficacy in the treatment of COVID-19 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 the viral infection. However, the outcome of passive plasma therapy is
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) that are generated from the plasma from
convalescent patients may provide a more specific immune response. In addition, antibodies with 
a high affinity to the virus can be selected (Zhou and Zhao 2020; Cao et al 2020). Currently, 
first-in-human (FIH) studies have been initiated for > 10 SARS-CoV-2 neutralizing antibodies
(neutralizing mAbs or cocktails of neutralizing mAbs) worldwide (Renn et al 2020; data from 
ClinicalTrials), including BGB-DXP593, the sponsor’s most potent neutralizing mAb.
BGB-DXP593 is currently being tested in healthy subjects (Study BGB-DXP593-101,
NCT04532294) and, as planned, will be evaluated in patients with mild to moderate COVID-19
(Study BGB-DXP593-102, NCT04551898). Regeneron and Eli Lilly have requested emergency 
use approval for REGN-COV2 and bamlanivimab (LY-CoV555), respectively. However, except 
for Eli Lilly’s bamlanivimab, which has recently been granted the emergency use authorization
from the FDA, no SARS-CoV-2-specific neutralizing mAbs have been approved so far;
therefore, neutralizing antibodies that effectively block virus entry into host cells are urgently 
needed.
1.2.
BGB-DXP604 as a SARS-CoV-2 Neutralizing Monoclonal Antibody
BGB-DXP604 (also named DXP-604, BD-604, and WBP2316) is a potent neutralizing mAb 
identified by high-throughput single-cell sequencing of convalescent patients’ B cells. 
BGB-DXP604 binds to the spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2
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with high specificity and affinity, and efficiently blocks the binding of RBD to its receptor, 
angiotensin-converting enzyme 2 (ACE2), thus preventing the virus from entering host cells. 
1.2.1.
Summary of Relevant Nonclinical Data With BGB-DXP604
1.2.1.1.
Pharmacology
BGB-DXP604 binds to the S-protein RBD of SARS-CoV-2 with high specificity and affinity, as 
demonstrated by target-binding assays and surface plasmon resonance characterization 
(equilibrium dissociation constant [KD] = 0.18 nM). BGB-DXP604 efficiently blocks the binding 
of RBD to its receptor, ACE2, with a concentration for inhibition of 50% maximal activity (IC50)
of 1.64 nM in a competition enzyme-linked immunosorbent assay. 
The crystal structure of the BGB-DXP604 antigen-binding fragment (Fab) in a complex with 
RBD suggests that BGB-DXP604 would interfere with the interaction between RBD and ACE2. 
The structure shows that 2 critical aromatic residues (Phe58 in CDRH2 and Tyr102 in CDRH3) 
of BGB-DXP604 likely contribute to its higher affinity interaction with the RBD. In another 
co-crystallization study, the BGB-DXP604 Fab was able to bind to RBD together with the
BGB-DXP593 Fab and form a Y-shaped tripartite complex, with the BGB-DXP604 Fab and 
BGB-DXP593 Fab attacking the RBD from opposite sides
In cell-based assays, BGB-DXP604 potently inhibits SARS-CoV-2 infections in both 
pseudovirus and authentic virus systems, with an IC50 of 0.024 nM (0.0036 μg/mL) and 1.27 nM
(0.19 μg/mL), and a concentration for inhibition of 99% maximal activity (IC99) of 2.37 nM
(0.355 μg/mL) and 3.13 nM (0.47 μg/mL), respectively. BGB-DXP604 has wild-type 
immunoglobulin G1 (IgG1) fragment crystallizable (Fc) region, which exhibits a similar binding 
profile as regular IgG1 antibodies in terms of binding to gamma Fc receptors (FcγRs) and 
complement component 1q (C1q), suggesting competent functions of antibody effector. 
The neutralization efficacy of BGB-DXP604 against SARS-CoV-2 was assessed in human 
ACE2 (hACE2) transgenic mice model. The in vivo experiment showed that BGB-DXP604
could provide strong therapeutic efficacy and prophylactic protection against SARS-CoV-2 in a
hACE2 transgenic mice model.
In hACE2 transgenic mice, BGB-DXP604 led to a dose-dependent reduction in the viral load 
when 10, 20, and 40 mg/kg BGB-DXP604 were injected 2 hours after the infection, with up to an
approximately 100-fold reduction in the 40 mg/kg group. Additionally, the body weights 
remained unchanged over a course of 4 days, suggesting that BGB-DXP604 maintained the 
fitness of the infected mice.
Please refer to the BGB-DXP604 Investigator’s Brochure for additional details regarding 
nonclinical studies of BGB-DXP604.
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1.2.1.2.
Toxicology
The toxicity and pharmacokinetic/toxicokinetic (PK/TK) profile of BGB-DXP604 administered 
by intravenous infusion was characterized in an 18-day repeat-dose toxicology study followed by 
a 28-day recovery period in cynomolgus monkeys. Tissue cross-reactivity was evaluated in a
study using normal frozen tissues from humans. Cytokine release responses were evaluated in a
study using human peripheral blood mononuclear cells (PBMCs). All data collection and 
analyses have been completed in these studies except for the cytokine analysis, antidrug antibody 
(ADA) analysis, and recovery phase data in the 18-day repeat-dose toxicity study. However, 
based on the available data, the yet unavailable information is not expected to have an impact on 
the toxicity results and the data interpretation.
The 18-day repeat-dose toxicity study was conducted in cynomolgus monkeys at the doses of 
0 (vehicle control), 30 mg/kg, 100 mg/kg, or 300 mg/kg once every week for 3 doses. No
mortality was observed throughout the study. No treatment-related findings or changes were 
observed, which included clinical observations, body weights, food consumption, body 
temperature, ophthalmology, electrocardiogram (ECG), blood pressure, neurological signs, 
clinical pathology (hematology, coagulation, serum chemistry and urinalysis), gross lesions, 
organ weights, or histopathology. No treatment-related changes in the vital functions of the
cardiovascular, respiratory, or central nervous systems were observed. 
The systemic exposure, which was evaluated by area under the concentration-time curve (AUC) 
from time zero to the 168 hours (AUC0-168h) and maximum observed concentration (Cmax),
appeared to increase dose proportionally without apparent sex differences. A slight drug 
accumulation (approximately 2-fold) was noted after weekly repeated doses for 3 doses. Based 
on the available data, the no observed adverse effect level (NOAEL) is considered 300 mg/kg in 
this study.
In the study for tissue cross-reactivity, using the immunohistochemical method, no specific 
binding of BGB-DXP604 was detected in human tissues. No apparent BGB-DXP604-specific 
cytokine releases were detected in human PBMCs.
Please refer to the BGB-DXP604 Investigator’s Brochure for more detailed information on the 
toxicology of BGB-DXP604.
1.2.2.
Summary of Relevant Clinical Experience With BGB-DXP604
This is the FIH study of BGB-DXP604. No clinical data are available.
1.3.
BGB-DXP593 as a SARS-CoV-2 Neutralizing Monoclonal Antibody
BGB-DXP593 (also named DXP593, BD-368-2, and WBP2281) is another neutralizing mAb 
with a pharmacologic mechanism similar to that of BGB-DXP604 but with different binding 
sites and more potent neutralization ability.
1.3.1.
Summary of Relevant Nonclinical Data With BGB-DXP593
1.3.1.1.
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 
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In the 14-day repeat-dose toxicology study in monkeys with doses ≤300 mg/kg, no apparent 
toxicity was noted. No specific safety concerns were observed in the vital functions of the 
cardiovascular, respiratory, or central nervous systems in monkeys. No specific tissue 
cross-reactivity with BGB-DXP593 was noted in either normal monkey or human tissues. 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.
1.3.2.
Summary of Relevant Clinical Experience With BGB-DXP593
A FIH study of BGB-DXP593 is being tested in healthy subjects. A Phase 2 study of 
BGB-DXP593 in patients with mild to moderate COVID-19 will begin recruiting soon.
1.4.
Study Rationale
1.4.1.
Rationale for Matching Placebo as the Comparator
In this study, normal saline (ie, solution of 0.9% sodium chloride) will be used as placebo. The 
volume of normal saline will be identical to the volume of each study drug (ie, BGB-DXP604 or 
BGB-DXP593). A placebo is being used to preserve the scientific integrity of the study and 
reduce any potential observational or performance bias. 
1.4.2.
Rationale for Selection of BGB-DXP604 Dose
1.4.2.1.
Allometric Scaling for Human Pharmacokinetics Projection
Serum concentration-time profiles from 30 cynomolgus monkeys that received repeated doses of 
BGB-DXP604 at 30 mg/kg, 100 mg/kg, or 300 mg/kg once every week for 3 doses 
(Section 1.2.1.2) were used in a population PK analysis with NONMEM® Version 7.3
(ICON plc; Dublin, Ireland).
A 2-compartment model with first-order elimination described the PK data well. Between-animal 
variability was estimated for clearance (CL) and volume of distribution (Vz). A proportional 
error model was used. Human PK parameters were obtained by scaling respective cynomolgus 
monkey PK parameters multiplied by the ratio of body weight (human to monkey) and taken to 
the power of 0.75 for clearance and intercompartmental clearance and 1.0 for the central and 
peripheral compartment volumes (Mahmood and Balian 1999).
The serum concentration-time profiles in humans for BGB-DXP604 were simulated using R 
version 3.6.1 software (Figure 1). The cynomolgus monkey PK parameters and projected human 
PK parameters are shown in Table 1.
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Figure 1:
Simulated BGB-DXP604 Serum and Lung (Assuming 1% Biodistribution) 
Concentration-Time Profiles in Humans
Abbreviation: IC99, concentration of BGB-DXP604 required to achieve 99% inhibition of host cell infection in vitro 
in a pseudovirus virus neutralization assay 
Notes: More details on the IC99 results are provided in Section 1.2.1.1.
The solid lines represent for projected serum concentrations. The dashed lines represent for projected lung 
concentrations assuming 1% biodistribution. Please refer to the BGB-DXP604 Investigator’s Brochure for more 
detailed information on assuming 1% biodistribution.
Table 1:
BGB-DXP604 Population PK Parameter Estimates in Cynomolgus Monkeys 
and Projected PK Parameters in Humans
Parameter (units)
Cynomolgus Monkey
Human
Projection
Estimate
% RSE
CL (L/h)
0.00085
6.1
0.0090
Vc (L)
0.162
4.5
3.79
Q (L/h)
0.0029
8.4
0.031
Vp (L)
0.0822
7.9
1.92
IIV CL (%)
30.1
15.0
NA
IIV Vc (%)
26.9
12.6
NA
Residual variability (%)
8.8
3.6
NA
Abbreviations: CL, clearance; h, hour; IIV, inter-individual variability; NA, not applicable; PK, pharmacokinetic; 
Q, intercompartmental clearance; RSE, relative standard error; Vc, volume of central compartment; Vp, volume of 
peripheral compartment.
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
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1.4.2.2.
Recommendation of the Starting Dose of BGB-DXP604 in Healthy Subjects
A single dose of BGB-DXP604 at 10 mg/kg as the starting dose is proposed for this Phase 1
study for BGB-DXP604. The selection of this dose was based on the NOAEL approach and is
supported by safety margins as described below.
Based on the toxicology evaluation in an 18-day repeat-dose study in cynomolgus monkeys, no
apparent toxicity was noted at doses ≤300 mg/kg; no specific safety concerns were identified in 
the vital functions of the cardiovascular, respiratory, or central nervous systems in monkeys
(Section 1.2.1.2). Therefore, the NOAEL was determined to be 300 mg/kg. In addition, no
specific tissue cross-reactivity with BGB-DXP604 was noted in human tissues. No apparent 
BGB-DXP604-specific cytokine release was detected in human PBMCs. Furthermore, the 
sponsor also has prior clinical experience with the similar neutralizing antibody BGB-DXP593,
which binds to the same virus target but at a different site. BGB-DXP593 has been administered 
safely in healthy human subjects at a dose of 30 mg/kg intravenously (Study BGB-DXP593-101,
NCT04532294).
Based on the above discussion, a safety factor of 10 was considered appropriate for the
maximum recommended starting dose (MRSD) estimated as 30 mg/kg (body-weight based) 
(FDA CDER 2005). The proposed starting dose level of 10 mg/kg is 3 times lower than the 
MRSD.
In addition, based on the AUC from time zero to 168 hours (AUC0-168h) and Cmax after the second
dose at 300 mg/kg in cynomolgus monkeys (ie, NOAEL in the toxicity study), the projected 
safety margins at the proposed starting dose of 10 mg/kg are 22.2 and 47.2, respectively
(Table 2), which reflects favorably on the safety profile of BGB-DXP604.
Please refer to the BGB-DXP604 Investigator’s Brochure for more detailed information on 
projected human concentrations.
Table 2:
Projected Safety Margins at Proposed Doses in Humans
Safety Margin
BGB-DXP604 Dose (mg/kg)
10
30
60
AUC based
22.2
7.4
3.7
Cmax based
47.2
15.7
7.9
Abbreviations: AUC, area under concentration-time curve; Cmax, maximum observed concentration 
Note: The proposed starting dose level is 10 mg/kg; safety margins to 60 mg/kg dose are provided for reference.
1.4.3.
Rationale for the Selection of BGB-DXP593 Dose
The proposed dose of 30 mg/kg BGB-DXP593 is based on safety experience in the healthy 
subject study BGB-DXP593-101.
1.4.4.
Rationale for the Combination of BGB-DXP604 and BGB-DXP593
Both BGB-DXP604 and BGB-DXP593 proteins are neutralizing antibodies that block the entry 
of virus particles into the host cell by interfering with the interaction between the RBD and 
human ACE2 receptor. BGB-DXP604 and BGB-DXP593 can bind simultaneously to the
different binding epitopes on the SARS-CoV-2 S-protein. Distinct binding sites would
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1.6.
Study Conduct
This study will be conducted in compliance with the protocol approved by the Institutional 
Review Board (IRB) or Independent Ethics Committee (IEC) and in accordance with Good 
Clinical Practice (GCP) standards.
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2.
STUDY OBJECTIVES AND STUDY ENDPOINTS
2.1.
Study Objectives
2.1.1.
Primary Objective
x
To investigate the safety and tolerability of BGB-DXP604 alone and in combination 
with BGB-DXP593 in healthy subjects
2.1.2.
Secondary Objectives
x
To characterize the PK profile of BGB-DXP604 when given alone in healthy subjects
x
To characterize the PK profiles of BGB-DXP604 and BGB-DXP593 when given in 
combination in healthy subjects
x
To evaluate the potential immunogenicity of BGB-DXP604 when given alone in 
healthy subjects
x
To evaluate the potential immunogenicity of BGB-DXP604 and BGB-DXP593 when 
given in combination in healthy subjects
2.2.
Study Endpoints
2.2.1.
Primary Endpoint
x
Incidence and severity of treatment-emergent adverse events (TEAEs) and 
treatment-emergent serious adverse events (SAEs)
2.2.2.
Secondary Endpoints
x
Changes from baseline in vital signs and 12-lead ECG parameters
x
Incidence and magnitude of clinical laboratory abnormalities
x
Characterize PK concentration-time profile and PK parameters of BGB-DXP604 and 
BGB-DXP593: Cmax, AUCt, AUCinf, AUC0-29, tmax, t1/2, CL, and Vz as appropriate
x
Clinical immunogenicity of BGB-DXP604 and BGB-DXP593 evaluated through the 
detection of ADAs over time
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3.
STUDY DESIGN
3.1.
Summary of Study Design
This is a Phase 1, randomized, double-blind, placebo-controlled study to investigate the safety, 
tolerability, PK, and immunogenicity of BGB-DXP604 alone and in combination with 
BGB-DXP593 in healthy subjects.
After providing written informed consent, subjects will complete all screening assessments. 
After being confirmed as eligible, subjects will be sequentially enrolled for 2 cohorts of different 
dose levels (referred to as Part 1). Two dose levels are planned for eligible subjects to receive a 
single intravenous dose of study drug (ie, BGB-DXP604 or placebo) at 10 mg/kg or 30 mg/kg, 
respectively.
Enrollment will begin at the 10 mg/kg dose level. Each dose level of study drug evaluated may 
be referred to as a cohort or dose level.
In Part 2, the combination of BGB-DXP604 and BGB-DXP593 will be tested in eligible 
subjects. Subjects enrolled in Cohort 2A will either receive the combination of BGB-DXP604 
and BGB-DXP593 or placebo (ie, the normal saline with volume equal to BGB-DXP604 or
BGB-DXP593 via separate intravenous infusions). The doses of BGB-DXP604 and 
BGB-DXP593 will be recommended by SMC and not exceed 30 mg/kg for each study drug.
In this study, after the last subject in the current cohort has received the study drug and has been 
followed up for ≥5 days, the Safety Monitoring Committee (SMC) will review the available 
safety and laboratory data. The next cohort will be initiated after the SMC review. The dose level 
of BGB-DXP604 in Cohort 1B and Cohort 2A may be adjusted based on SMC recommendation.
In each cohort, eligible subjects will be randomized at a 3:1 ratio (6 active: 2 control) to the
active arm for receiving the study drug(s) (ie, BGB-DXP604 alone or the combination of 
BGB-DXP604 and BGB-DXP593) or to the control arm for receiving placebo, respectively.
For safety reasons, the sentinel dosing will be adopted for each cohort. In other words, 2 eligible 
subjects will be randomized at a 1:1 ratio (1 active: 1 control) to receive the study drug(s) or
placebo on Day 1; the remaining subjects will be randomized at a 5:1 ratio (5 active: 1 control) to 
receive the study drug(s) or placebo ≥48 hours later, provided that satisfactory safety and 
tolerability has been demonstrated for the first 2 subjects randomized and dosed in the current 
cohort.
The planned cohorts and number of subjects in each cohort are provided in Table 3. Up to 
30 subjects (including possible replacement) will be enrolled in the study, which will be 
conducted in 1 to 2 centers in Australia. 
Subjects are expected to be available for follow-up visits until Day 113 of the study. Subjects 
will be replaced if they cannot complete the infusion or they do not receive any study drug after 
randomization. Subjects may be replaced if they discontinue from the study before Day 29.
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Table 3:
Planned Cohorts and Number of Subjects in Each Cohort
Part
Cohort
Number of Subjects in Each Cohort
Active Arm
Control Arm 
(Normal Saline)
1: BGB-DXP604 alone
1A: 10 mg/kg
6
2
1B: 30 mg/kg a
6
2
2: BGB-DXP604
+ BGB-DXP593
2A: 30 mg/kg b BGB-DXP604 
+ 30 mg/kg b BGB-DXP593
6
2
Abbreviation: SMC, Safety Monitoring Committee.
a
The dose level of BGB-DXP604 in Cohort 1B may be adjusted based on SMC recommendation.
b
The doses of BGB-DXP604 and BGB-DXP593 in Cohort 2A will be recommended by SMC and not exceed 
30 mg/kg for each study drug.
Study Assessments
Subjects will be monitored throughout the study for safety, tolerability, PK, and immunogenicity 
of BGB-DXP604 and BGB-DXP593.
Assessments of safety will include adverse events (AEs), SAEs, clinical laboratory tests, 
physical examinations, vital signs, and ECGs. An SMC will periodically monitor safety data.
AEs will be graded for severity per the current version of the National Cancer Institute-Common 
Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0). Refer to Section 9 for 
additional and specific information regarding AE monitoring and reporting.
PK and ADA sampling will be collected at specific intervals from Day 1 to Day 113
(Appendix 2 and Appendix 3).
Study procedures and assessments are further detailed in Section 7 and Section 8, respectively, 
and the Schedule of Assessments can be found in Appendix 1. Specific details regarding dose 
escalation are described in the following sections.
3.2.
Details of Dose Escalation (Part 1)
3.2.1.
Starting Dose and Dose Escalation Approach (Part 1)
Dose escalation will occur sequentially in increasing dose levels of study drug (ie, BGB-DXP604 
or placebo). Each dose level of study drug evaluated may be referred to as a cohort or dose level. 
Only 1 dose of BGB-DXP604 or placebo will be administered to each subject in each cohort.
The starting dose level will be 10 mg/kg. This dose level was chosen based on an overall 
assessment of toxicology data in cynomolgus monkeys (more details are provided in 
Section 1.2.1.2).
Two ascending dose levels for study drug at single doses of 10 mg/kg and 30 mg/kg are planned
in Part 1. The projected safety margins at the proposed dose levels reflect favorably on the safety
profile of BGB-DXP604 and show that a dose up to 30 mg/kg is expected to provide adequate 
(> 2 fold) safety margins (Table 2).
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3.2.2.
Rules for Dose Escalation (Part 1)
The study design allows a gradual dose escalation with intensive safety monitoring to ensure the 
safety of the subjects. In this single dose escalation study with healthy subjects, the maximum 
factor for the first dose escalation step will be 3, the maximum factor for the following potential 
dose escalation step will be 3.
After the last subject in the current cohort has received the study drug and has been followed up 
for ≥5 days, the SMC will review the available safety and laboratory data. The next cohort will 
be initiated after the SMC review, in the absence of meeting any prespecified pausing criteria 
(more details are provided in Section 3.4).
An appropriate interval (≥5 days) between dose levels will require a timely review and 
evaluation of safety data (eg, AE profile, vital signs, 12-lead ECG, cardiac telemetry, and clinical 
laboratory safety tests) before proceeding to the next higher dose level. 
Following the review of data from subjects under a dose level, the timing of assessments and/or 
blood samples may be adjusted for subsequent dose level. Additional assessments or sampling 
times may be added or removed if indicated by the data; however, the maximum blood volume
taken from each subject will not exceed 450 mL.
3.3.
Initiation of Combination Cohort (Part 2)
In Part 2, the combination of BGB-DXP604 and BGB-DXP593 will be tested in eligible 
subjects. After the last subject in Cohort 1B has received the study drug and has been followed 
up for ≥5 days, the SMC will review the available safety and laboratory data. Cohort 2A will be 
initiated after the SMC review, in the absence of meeting any prespecified pausing criteria (more 
details are provided in Section 3.4).
Subjects enrolled in Cohort 2A will either receive the combination of BGB-DXP604 and 
BGB-DXP593 or placebo (ie, the normal saline with volume equal to BGB-DXP604 or 
BGB-DXP593 via separate intravenous infusions). The doses of BGB-DXP604 and 
BGB-DXP593 will be recommended by SMC and not exceed 30 mg/kg for each study drug.
An interval of ≥5 days between Cohort 1B and Cohort 2A will allow for a timely review and 
evaluation of safety data (eg, AE profile, vital signs, 12-lead ECG, cardiac telemetry, and clinical 
laboratory safety tests) before proceeding to Cohort 2A.
After the review of data from subjects in Cohort 1B, the timing of assessments and/or blood 
samples may be adjusted for Cohort 2A. Additional assessments or sampling times may be added 
or removed if indicated by the data; however, the maximum blood volume taken from each 
subject will not exceed 450 mL.
3.4.
Criteria for Pausing Drug Administration and New Enrollment
In this study, the SMC will review the safety and laboratory data for each cohort. If an increased 
risk for the subjects is suspected during the study, the SMC will recommend to immediately 
suspend the recruiting of additional participants. 
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Administration of study drug(s) and enrollment of new subjects will be paused for the current 
cohort if any of the following events occurs: 
x
One or more ≥Grade 4 TEAEs or treatment-emergent SAEs related to study drug(s)
as assessed by the investigator in any subject or
x
One or more Grade 3 TEAEs related to study drug(s) as assessed by the investigator 
in ≥2 subjects in the same cohort.
The SMC may recommend keeping the current enrollment plan, opening a repeated cohort at the 
same dose of study drug(s), de-escalating to a lower dose of study drug(s), or terminating the 
study. For the repeated cohort at the same dose level and the cohort at the lower dose level, the 
number of subjects and randomization ratio will be the same as planned for each cohort.
If the TEAE(s) previously observed at the same dose level occurs again in a repeated cohort at 
the same dose level, no higher dose level will be tested in Part 1. If the same situation occurs in 
the repeated cohort in Part 2, no combination of higher doses will be tested.
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4.
SELECTION OF STUDY POPULATION
The specific eligibility criteria for the selection of subjects are provided in Section 4.1 and 
Section 4.2. The sponsor will not grant any eligibility waivers.
4.1.
Inclusion Criteria
Each subject must meet all the following inclusion criteria to be considered eligible for
participation in this study:
1. Male and female subjects 18 to 60 years of age, inclusive, at the time of signing the 
informed consent
2. Subjects are in good general health as determined by the investigator or medically 
qualified designee, based on a medical evaluation including medical history, physical 
examination, laboratory tests, and cardiac monitoring
3. Body weight ≥50 kg and body mass index (BMI) within the range 18 to 32 kg/m2
(inclusive)
Note: BMI = weight [kg] / (height [m])2
4. Negative SARS-CoV-2 serology test
5. Negative for COVID-19 based on the nasopharyngeal or oropharyngeal swab with the 
method of real-time reverse transcription-polymerase chain reaction (rRT-PCR)
6. Female subjects of childbearing potential must be willing to use a highly effective 
method of birth control (see Appendix 5) from the time of study enrollment until 
4 months after the single dose of study drug(s)
7. Male subjects with female partners of childbearing potential must be willing to use a 
highly effective method of birth control (see Appendix 5) from the time of study 
enrollment until 4 months after the single dose of study drug(s)
8. Able to provide written informed consent and can understand and agree to comply with 
the requirements of the study and the schedule of assessments.
4.2.
Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from this study.
Medical Histories or Conditions
1. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, 
endocrinological, hematological, or neurological disorders capable of significantly 
altering the absorption, metabolism, or elimination of drugs, constituting a risk to the 
subject when receiving the study drug; or interfering with the interpretation of data
2. Systolic blood pressure > 150 mmHg at screening
3. Any malignancy within the past 5 years except for basal cell or squamous carcinomas of 
the skin that has been resected with no evidence of metastatic disease for 3 years
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4. Any history of a severe allergic reaction before enrollment that has a reasonable risk of 
recurrence during the study
5. A medical history of SARS infection
6. Any acute fever disease or infections
7. Any chronic or clinically significant medical condition that, in the opinion of the 
investigator, would jeopardize the safety or rights of the subject, including but not limited 
to type 1 diabetes mellitus, chronic hepatitis; or clinically significant forms of: drug or 
alcohol abuse, asthma (except for childhood asthma), autoimmune disease, psychiatric 
disorders, or heart disease
8. Platelet disorder or other bleeding disorder may cause injection contraindication
9. Alanine aminotransferase and/or aspartate aminotransferase > 1.5 x upper limit of normal 
(ULN) 
10. Bilirubin > 1.5 x ULN (isolated bilirubin > 1.5 x ULN is acceptable if bilirubin is 
fractionated and direct bilirubin < 35%)
11. Current or chronic history of liver disease or known hepatic or biliary abnormalities (with 
the exception of Gilbert's syndrome or asymptomatic gallstones)
12. Average Fridericia’s formula (QTcF) > 450 ms (based on triplicate ECGs)
x
NOTE A: The QTc is the QT interval corrected for heart rate according to QTcF, 
and/or another method. It is either machine-read or manually over-read.
x
NOTE B: The specific formula used to determine eligibility or discontinuation for an 
individual participant should be determined before initiation of the study. In other 
words, several different formulas cannot be used to calculate the QTc for an 
individual participant and then the lowest QTc value used to include or discontinue 
that participant.
Prior/Concomitant Therapy
13. Previous receipt of a licensed or investigational biologic agent (such as monoclonal 
antibodies) within 3 months or 5 half-lives (whichever is longer) before the 
randomization
14. Previous receipt of a licensed or investigational nonbiologic agent (such as those derived 
from chemical synthesis) within 1 month or 5 half-lives (whichever is longer) before the 
randomization
15. Past or intended use of over-the-counter or prescription medication, including herbal 
medications, within 28 days before the randomization. Use of paracetamol, ibuprofen, 
and/or vitamins at the recommended dose will be allowed at the investigator’s discretion 
within 28 days before the randomization.
Prior/Concurrent Clinical Study Experience
16. Participation in ≥4 clinical studies within 12 months before the randomization
17. Previous participation in Study BGB-DXP593-101.
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Diagnostic Assessments
18. Positive HIV antibody test
19. Presence of hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody 
(HBcAb) at screening or within 3 months before the randomization
20. Positive hepatitis C antibody test result at screening or within 3 months before
randomization
NOTE: Participants with positive hepatitis C antibody due to prior resolved disease can 
be enrolled if a confirmatory negative hepatitis C RNA test is obtained.
21. Positive hepatitis C RNA test result at screening or within 3 months before randomization
NOTE: Test is optional and participants with negative hepatitis C antibody test are not 
required to also undergo hepatitis C RNA testing
22. Positive pre-study alcohol/drugs screen.
Other Exclusions
23. Immediate family history of seizures, epilepsy, brain or mental disease at the 
investigator’s discretion
24. The total volume of blood loss > 500 mL within 3 months before randomization
25. Sensitivity to any of the study drug or components thereof, or other allergy that, in the 
opinion of the investigator or medical monitor, contraindicates participation in the study
26. Anyone who smokes ≥15 cigarettes per day.
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5.
STUDY TREATMENT
5.1.
Formulation, Packaging, and Handling
5.1.1.
BGB-DXP604
BGB-DXP604 is a neutralizing mAb formulated for intravenous injection in a single-use vial 
(United States Pharmacopeia [USP] type I) containing 300 mg of antibody in 10 mL of buffered 
isotonic solution. BGB-DXP604 has been aseptically filled in single-use vials with a rubber 
stopper capped with an aluminum flip-off seal. Five single-use vials are packaged into each 
carton. The contents of the label on vials and cartons will be in accordance with all applicable 
local regulatory requirements, including Annex 13 of Pharmaceutical Inspection Co-operation 
Scheme Good Manufacturing Practice Guide (PIC/S GMP Guide 2018).
The study drug will be dispatched to the study center only after receipt of the required documents 
in accordance with applicable regulatory requirements and the sponsor’s procedures. The 
unblinded pharmacist(s) or designated personnel are responsible for maintaining the drug supply 
inventory and acknowledging receipt of all study drug shipments. The study drug must be stored 
in a secure area, with access limited to the authorized study center personnel and kept under 
physical conditions that are consistent with study drug-specific requirements. BGB-DXP604
must be stored at temperatures from 2℃to 8℃and protected from light. 
Refer to the Pharmacy Manual for details regarding intravenous administration, accountability, 
and disposal. Please also refer to the BGB-DXP604 Investigator’s Brochure for other details 
regarding BGB-DXP604.
5.1.2.
BGB-DXP593
BGB-DXP593 is a neutralizing mAb formulated for intravenous injection in a single-use vial 
(USP type I) containing 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 with
an aluminum flip-off seal. Five single-use vials are packaged into each carton. The contents of 
the label on vials and cartons will be in accordance with all applicable local regulatory 
requirements, including Annex 13 of Pharmaceutical Inspection Co-operation Scheme Good 
Manufacturing Practice Guide (PIC/S GMP Guide 2018).
The study drug will be dispatched to the study center only after receipt of the required documents 
in accordance with applicable regulatory requirements and the sponsor’s procedures. The 
unblinded pharmacist(s) or designated personnel are responsible for maintaining the drug supply 
inventory and acknowledging receipt of all study drug shipments. The study drug must be stored 
in a secure area, with access limited to the authorized study center personnel and kept under 
physical conditions that are consistent with study drug-specific requirements. BGB-DXP593 
must be stored at temperatures from 2℃ to 8℃ 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.
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5.1.3.
Placebo
The placebo for this study is normal saline (ie, solution of 0.9% sodium chloride) at the same 
volume as BGB-DXP604 or BGB-DXP593. The normal saline will be sourced and provided by 
the site. For further details, refer to the Pharmacy Manual for the matching placebo.
5.2.
Dosage, Administration, and Compliance
Planned dose level(s) for study drug(s) in each cohort are presented in Table 4.
Table 4:
Planned Dose Level(s) for Study Drug(s) in Each Cohort
Part 1: BGB-DXP604 Alone
Part 2: BGB-DXP604 + BGB-DXP593
Cohort 1A: 10 mg/kg BGB-DXP604
or placebo
Not applicable
Cohort 1B: 30 mg/kg a BGB-DXP604
or placebo
Cohort 2A: 30 mg/kg b BGB-DXP604 + 30 mg/kg b
BGB-DXP593 or placebo
Abbreviation: SMC, Safety Monitoring Committee.
a
The dose level of BGB-DXP604 in Cohort 1B may be adjusted based on SMC recommendation.
b
The doses of BGB-DXP604 and BGB-DXP593 in Cohort 2A will be recommended by SMC and not exceed 
30 mg/kg for each study drug.
Eligible subjects will receive the administration of study drug(s) at dose level(s) as above or
matching placebo for 30 to 60 minutes.
For Cohort 2A, BGB-DXP593 infusion should be administered intravenously first, followed by 
the intravenous infusion of BGB-DXP604. BGB-DXP604 infusion should be given ≥30 minutes 
after the completion of the BGB-DXP593 infusion. The matching placebo for Cohort 1A and 
Cohort 1B is normal saline at a volume equal to BGB-DXP604 only; for Cohort 2A, normal 
saline solutions at a volume equal to BGB-DXP604 or BGB-DXP593 are needed and will be 
administrated at the same sequence as BGB-DXP604 or BGB-DXP593. The dose of study 
drug(s) will be based on the subject’s actual body weight 1 day before the administration of
study drug(s) (Day -1).
As a routine precaution, subjects must be monitored for ≥2 hours after the infusion of study 
drug(s) in an area with resuscitation equipment and emergency agents. The study drug(s) must 
not be administered concurrently with any other drug.
For safety reasons, the first 2 subjects randomized and dosed in each cohort will be monitored 
for ≥48 hours before the remaining subjects receive the same dose of study drug(s).
In this study, after the last subject in the current cohort has received the study drug and has been 
followed up for ≥5 days, the SMC will review the available safety and laboratory data. The next 
cohort will be initiated after the SMC review.
Accurate records of the study drug(s) received, dispensed, returned, and disposed of should be 
maintained in the site’s Drug Inventory Log. Please refer to the Pharmacy Manual for details 
regarding study drug(s) management, drug preparation, storage, and administration.
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5.3.
Measures to Minimize Bias: Randomization and Blinding
Randomization
For each cohort, eligible subjects will be randomized at a 3:1 ratio (6 active: 2 control) to receive 
BGB-DXP604 with or without BGB-DXP593 or placebo. Sentinel dosing will be adopted for 
each cohort; the randomization ratios for sentinel dosing are provided in Section 3.1.
Site personnel will access the Interactive Response Technology (IRT) system to randomize the 
treatment assignment. All subjects will receive a unique study subject number. Up to 
2 replacements will be allowed for each subject (eg, the original subject in one treatment arm is 
allowed to have a 2nd replacement when the 1st replacement is withdrawn). A subject for 
replacement will be assigned to the same treatment as the subject he/she replaces.
Blinding
The study is designed as double-blind for the subjects and the investigator (as well as the site 
personnel) in order to eliminate observational or performance bias. This is to avoid the 
systematic differences in assessments on the subject’s treatment (ie, BGB-DXP604 with or
without BGB-DXP593 or placebo). 
The single dose of study drug(s) will be prepared by unblinded pharmacist(s) and administered 
by blinded study nurse(s). The intravenous infusion of BGB-DXP604, BGB-DXP593, and 
placebo will be colorless. All follow-up evaluations will be performed by blinded clinic staff.
At the study site, access to the treatment information for each subject is restricted to the 
unblinded pharmacist(s). Persons directly involved in the clinical conduct of the study will not 
have access to the treatment allocation before database lock.
Regarding the sponsor, the database of this study will be handled as open label, meaning that the 
study functions of the sponsor are unblinded (including the medical monitor and study team 
members from Pharmacovigilance/Drug Safety, Clinical Pharmacology, and Biostatistics with 
other members as appropriate). The objectives of the study are expected not to be affected.
Unblinding
1. Emergency unblinding 
In case of an emergency, the investigator has the sole responsibility for determining if the
unblinding of a subject’s treatment assignment is warranted. Subject safety must always be the 
first consideration in making such a determination. Emergency unblinding for AEs may be 
performed through an IRT system.
If the investigator decides that unblinding is warranted, the investigator should make every effort 
to contact the medical monitor before unblinding a subject’s treatment assignment unless this 
could delay emergency treatment of the subject. If a subject’s treatment assignment is unblinded, 
the sponsor must be notified immediately.
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2. Inadvertent unblinding 
Every effort will be made to blind both the subject and the investigator to the identity of 
BGB-DXP604, BGB-DXP593, or placebo, but inadvertent unblinding of a subject may occur. If 
an investigator, site personnel performing assessments, or subject is unblinded, the unblinding 
will not be the sufficient cause for that subject to be discontinued from study or excluded from 
any analyses.
5.4.
Incorrect Administration
Any incorrect administration of the study drug(s) should be noted in the subject’s medical record 
and on the appropriate electronic case report form (eCRF).
AEs due to an incorrect administration of the study drug(s) 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 9.7.2. Supportive care should be 
administered as appropriate.
5.5.
Dose Interruption or Modification
There will be no dose reduction of study drug(s).
A subject may temporarily interrupt their infusion of study drug(s) or discontinue their infusion 
of study drug(s) due to infusion-related reactions or other medical events. 
The subject should resume the study treatment within 2 hours of the infusion interruption if the 
AE is resolved or recovered to Grade 1 (whichever is more severe). If the subject is unable to 
resume the study drug(s) within 2 hours of the infusion interruption, then the subject should be 
discontinued from the study treatment and the subject will be replaced. The treatment 
modification for infusion-related reactions is provided in Section 9.8.1.
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6.
PRIOR AND CONCOMITANT THERAPY
6.1.
Prior Therapy
The exclusion criteria (Section 4.2) specify that:
x
subjects must not have received any licensed or investigational biologic agent (such 
as monoclonal antibodies) within 3 months or 5 half-lives (whichever is longer) 
before randomization
x
subjects must not have received any licensed or investigational nonbiologic agent 
(such as those derived from chemical synthesis) within 1 month or 5 half-lives 
(whichever is longer) before randomization
x
subjects must not have received any over-the-counter or prescription medication, 
including herbal medications, within 28 days before randomization. Use of 
paracetamol, ibuprofen, and/or vitamins at the recommended dose will be allowed at 
the investigator’s discretion within 28 days before randomization.
6.2.
Concomitant Therapy
As healthy subjects are enrolled in the study, concomitant therapy is not allowed during the 
study. If medical events (such as infusion-related reactions or severe hypersensitivity) occur 
during the study period, the subjects may receive appropriate medical treatment. The 
management of infusion-related reactions and severe hypersensitivity is provided in Section 9.8.
All concomitant medications taken during the study will be recorded in the eCRF with indication 
and dates of administration. 
6.3.
Potential Interactions Between BGB-DXP604 or BGB-DXP593 and 
Concomitant Medications
The potential for drug-drug interaction between BGB-DXP604 or BGB-DXP593 and 
small-molecule drug products is very low, given that BGB-DXP604 and BGB-DXP593 are
monoclonal antibodies. Because BGB-DXP604 and BGB-DXP593 are expected to degrade into 
amino acids and recycled into other proteins, they are unlikely to have an effect on drug 
metabolizing enzymes or transporters.
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7.
STUDY PERIODS, VISITS, OR PROCEDURES
Study periods, visits, and procedures are summarized in the following subsections. The timing of 
all study procedures is provided in the Schedule of Assessments (Appendix 1).
7.1.
Screening Period
Screening evaluation will be performed within 28 days before administration of study drug(s). A 
subject who agrees to participate in this study will sign the informed consent form (ICF) before 
undergoing any study-specific procedures. Refer to Section 8.1 for instructions regarding 
screening assessments.
7.1.1.
Informed Consent
Voluntary, written informed consent for participation in the study must be obtained before any 
study-specific procedures are performed. ICFs for enrolled subjects and for subjects who are 
screened but not enrolled will be maintained at the study site. Consent must be obtained using 
the most current version of the form approved by the IEC/IRB.
For subjects who provide informed consent and who subsequently do not meet eligibility criteria 
or who withdraw consent before administration of study drug(s), study site personnel should 
document this as a screen failure in the subject’s source documents. The documentation should 
include demographics and medical history, the reason for screen failure, the eligibility criteria 
reviewed, procedures performed.  
7.2.
Enrollment
7.2.1.
Confirmation of Eligibility
The investigator will assess and confirm the eligibility of each subject. All screening results and 
relevant medical history must be available before eligibility can be determined. All inclusion 
criteria must be met and none of the exclusion criteria may apply. No eligibility waivers will be 
granted. 
7.2.2.
Subject Numbering
After informed consent is obtained, a unique subject number will be assigned to a potential study 
participant.
7.3.
Check-in (Day -1)
The enrolled subjects will be admitted ≥12 hours before the administration of study drug(s). On 
the day of admission, screening for alcohol/drugs, a review of the inclusion/exclusion criteria,
laboratory assessments of hematology, clinical chemistry, coagulation, urinalysis, and safety 
assessments of vital signs and weight will be performed. Smoking will be not allowed during the 
inpatient stay.
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7.4.
Randomization 
Site personnel will access the IRT system to randomize the treatment assignment. 
Randomization will occur after admission on Day -1 and before the administration of study 
drug(s) on Day 1.
7.5.
Treatment (Day 1)
The enrolled subjects will be treated as described in Section 5.2. The study procedures on Day 1
are shown in Appendix 2. Refer to Section 7.7 for additional considerations regarding treatment 
withdrawal.
7.6.
Follow-up Period
The follow-up period starts the next day after infusion of study drug(s) and continues until 
Day 113 of the study. All AEs, including SAEs, will be collected as described in Section 9.7.
7.6.1.
Check-out (Day 3)
The subjects will be discharged 3 days after the administration of study drug(s). Before the 
discharge, the procedures and assessments specified in Appendix 1 should be completed.
7.6.2.
End-of-Study Visit
Subjects who permanently discontinue from the study will be asked to return to the study center 
for the End-of-Study (EOS) Visit, which is required to be conducted ≤7 days after premature 
study discontinuation. The Day 113 Visit is the EOS Visit for subjects who complete all
previously planned study visits.
If a subject refuses to return for the EOS Visit or is unable to do so, every effort should be made 
to contact the subject by telephone to determine their health status.
7.6.3.
Safety Follow-up Visit for Premature Study Discontinuation
If a subject discontinues the study ≤30 days after the administration of study drug(s), a Safety
Follow-up Visit will be conducted 30 days after study drug(s) administration. If premature 
discontinuation from study occurs ≤7 days before 30 days after the administration of study 
drug(s), the Safety Follow-up Visit may be combined with the EOS Visit if appropriate. A visit 
window of ± 3 days will be allowed for the Safety Follow-up Visit. 
7.6.4.
Lost to Follow-up
If attempts to contact a subject by telephone are unsuccessful, additional attempts should be 
made during the study to complete study-related assessments and record outstanding data. It may 
be possible to obtain the information from other contacts, such as referring physicians or primary 
care providers. 
Attempts to contact should be documented in the subject’s source documents. If a subject cannot 
be contacted despite all attempts, the subject will be considered lost to follow-up.
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7.7.
Premature Discontinuation From Study Treatment or From the 
Study
7.7.1.
Subject Premature Discontinuation From the Study Treatment
Eligible subjects will receive the administration of study drug(s) and they have the right to 
discontinue the study drug(s) at any time for any reason during the study treatment. In addition, 
the investigator has the right to discontinue a subject from the study drug(s) at any time during 
the study treatment. Subjects who discontinue the study treatment should follow the procedures 
and the assessments specified in EOS Visit (Section 7.6.2). Subjects who could not complete the 
infusion or did not receive any study drug after the randomization should be replaced.
The primary reason for discontinuation from the study treatment should be documented on the 
appropriate eCRF. Subjects may discontinue from the study treatment for reasons that include, 
but are not limited to, the following:
x
Withdrawal of consent
x
The investigator or sponsor determines it is in the best interest of the subject
x
Significant or persistent AE(s) as described in Section 9.8.
7.7.2.
Subject Premature Discontinuation From the Study
Subjects may discontinue from the study for reasons that include, but are not limited to, the 
following:
x
Subject withdrawal of consent
x
Study termination by sponsor
x
Lost to follow-up
x
Positive for COVID-19
Subjects may voluntarily withdraw consent from the study at any time. A subject who 
discontinues from the study before Day 29 may be replaced.
7.8.
End of Study
The end of study is defined as the timepoint when the final data for a clinical study were 
collected, which is after the last subject has made the final visit to the study center. 
Alternatively, the end of study is when the sponsor decides to terminate the study. The sponsor 
has the right to terminate this study at any time. Reasons for terminating the study early include,
but are not limited to, the following: 
x
The incidence or severity of AEs in this or other studies on BGB-DXP604 or 
BGB-DXP593 indicates a potential health hazard to subjects
x
Overall subject enrollment is unsatisfactory
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The sponsor will notify the investigator if a decision is made to terminate the study. Should this 
be necessary, prematurely discontinued subjects must be seen for an EOS Visit as described in 
Section 7.6.2.
The investigators may be informed of additional procedures to be followed to ensure that 
adequate consideration is given to the protection of the subject’s interests. The investigator will 
be responsible for informing IRBs/IECs of the early termination of the study.
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8.
STUDY ASSESSMENTS
A table of scheduled study assessments is provided in Appendix 1. Subjects will be closely 
monitored for safety and tolerability throughout the study. All assessments will be performed on 
the day of the specified visit and documented in the medical record for each subject. 
Where applicable, the study drug(s) will be administered only if the clinical assessment and 
laboratory test values have been reviewed and found to be acceptable per protocol guidelines.
8.1.
Screening Assessments
Screening evaluations will be performed within 28 days before receiving the study drug(s). The 
screening period begins when the ICFs were signed by the subjects. The investigator will assess 
subject eligibility according to the latest screening assessment results.
8.1.1.
Demographic Data, Medical History, and Prior Medications
Demographic data will include age or year of birth, gender, and race/ethnicity. 
Medical history includes any history of clinically significant disease, surgery history, 
reproductive status (ie, no childbearing potential or childbearing potential), and smoking history.
Prior medications include all medications (eg, prescription drugs, over-the-counter drugs, herbal 
medications) used by the subject within 28 days before administration of study drug(s).
8.2.
Safety Assessments
8.2.1.
Vital Signs
Vital signs will include measurements of body temperature (℃), pulse rate, respiratory rate, and 
blood pressure (systolic and diastolic). Pulse rate and blood pressure will be measured while the 
subject is in a supine position after resting for 10 minutes.
Height and weight will be measured at screening and weight will be measured again 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 v5.0 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 9.4 regarding AE definitions and reporting and 
follow-up requirements.
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8.2.3.
Laboratory Safety Tests
Samples for protocol-specified clinical chemistry, hematology, urinalysis, and coagulation 
profiles will be evaluated by a local laboratory. 
A pregnancy test will be performed for female subjects of childbearing potential during the 
study. Samples for pregnancy testing will also be assessed locally. The urine pregnancy test will 
be performed at the Screening Visit, and the next urine pregnancy test will be conducted after the 
admission on Day -1 and before administration of study drug(s) on Day 1. Female subjects of 
childbearing potential with negative results will be eligible to receive the study drug(s).
Afterwards, urine pregnancy test will be performed. A serum pregnancy test must be performed 
if the urine pregnancy test is positive or equivocal.
See Appendix 4 for the list of clinical laboratory tests to be performed and Appendix 1 for the 
timing and frequency. Additional tests may be performed at any time during the study as deemed 
necessary by the investigator or as required by local regulations. If required by local regulations, 
clinical laboratory evaluations performed by a local (instead of a central) laboratory are 
acceptable.
A detailed description of the procedures for sample collection, handling, storage, and shipment 
of the laboratory samples and all materials such as test tubes and labels are provided in the 
Laboratory Manual.
8.2.4.
Electrocardiograms
For safety monitoring purposes, the investigator must review, sign, and date all ECG tracings. 
Paper or electronic copies of ECG tracings (per local practice) will be kept as part of the 
subject’s permanent study file at the site.
The subject should rest in a semirecumbent or supine position for ≥10 minutes in the absence of 
environmental distractions that may induce changes in heart rate (eg, television, radio, 
conversation) before each ECG collection.
At each timepoint (see Appendix 1), 3 consecutive 12-lead ECGs will be performed 
approximately 2 minutes apart and within a maximum of 10 minutes to calculate heart rate and 
measure QT and QTcF intervals.
8.2.5.
Cardiac Telemetry
The cardiac telemetry will be performed from approximately 1 hour predose to 24 hours post 
dosing. The full disclosures will be maintained electronically by the site as part of the subject’s 
source documents.
8.2.6.
Adverse Events
AEs will be graded and recorded throughout the study according to NCI-CTCAE v5.0. 
Characterization of toxicities will include severity, duration, and time to onset. 
All AEs, including SAEs, will be collected as described in Section 9.7.
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8.2.7.
Serology
The testing of HBV/HCV serology (HBsAg, HBcAb, and HCV antibody) will be performed at 
screening. In the case of positive HCV antibody, the test of HCV RNA will be followed.
Blood from all subjects will be collected and tested for HIV antibody at screening. Those 
subjects with negative results can be enrolled. 
Specific IgG antibodies against SARS-CoV-2 in the serum of all subjects will be measured by 
quantitative or qualitative antibody testing. Those subjects with negative results can be enrolled. 
The tests mentioned above will be performed at a local laboratory.
8.2.8.
Virology
The nasopharyngeal or oropharyngeal swab will be collected during the screening and at the visit 
on Day 29. The nasopharyngeal or oropharyngeal swab will be tested by the method of rRT-PCR 
in a local laboratory for the qualitative detection of nucleic acid from SARS-CoV-2 in upper 
respiratory specimens. During the screening, those subjects who have negative results can be 
enrolled. 
If any subject has positive or suspected result during the study, the subject will be discontinued 
from the study and treated by following local practice. If the subject is unable to complete the 
EOS Visit, please see the procedures in Section 7.6.2 and Section 7.6.4.
8.3.
Pharmacokinetic Assessment and Antidrug Antibody Testing
Blood will be collected to characterize the PK profile of BGB-DXP604 or BGB-DXP593 using 
validated immunoassays. Blood samples will be collected for characterization of 
anti-BGB-DXP604 or anti-BGB-DXP593 antibodies. Validated screening and confirmatory 
assays will be employed to detect ADAs in the samples. Samples collected for analyses of blood 
concentration may also be used to evaluate safety or efficacy aspects related to concerns arising
during or after the study.
Blood sampling for PK and ADA will be collected at the timepoints specified in the PK and 
immunogenicity sampling schedule (Appendix 3).
The PK and ADA assays for BGB-DXP604 or BGB-DXP593 will be managed through a central 
laboratory. Refer to the laboratory manual for instructions regarding sample collection, handling, 
labeling, storage, and shipping of laboratory samples. The actual time of each sample collected 
will be captured to the nearest minute in the eCRF and recorded in the database.
8.4.
Visit Windows
The PK sampling schedule allows for a visit window of ± 1 day for the visits at Day 15, Day 22,
and Day 29, and a visit window of ± 2 days for the visits at Day 43, Day 57, Day 71, Day 85, and 
Day 113 (Appendix 1 and Appendix 3). All assessments will be performed on the day of the 
specified visit.
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8.5.
Unscheduled Visits
Unscheduled visits may be performed at any time at the subject’s or investigator’s request if 
there are any safety concerns. The date and reason for the unscheduled visit must be recorded in 
the source documentation.  
If an unscheduled visit is necessary to assess toxicity, then diagnostic tests may be performed 
based on the investigator’s assessment as appropriate, and the results of these tests should be 
recorded on the unscheduled visit eCRF.
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9.
SAFETY MONITORING AND REPORTING
The investigator is responsible for the monitoring and documentation of events that meet the 
criteria and definition of an AE or SAE as provided in this protocol.  
9.1.
Risks Associated With BGB-DXP604
This is the FIH study of BGB-DXP604. No clinical data are available yet and no risk associated 
with BGB-DXP604 has been identified. In the 18-day repeat-dose toxicology study, no apparent 
toxicity was observed in cynomolgus monkeys at doses of 30 mg/kg, 100 mg/kg, or 300 mg/kg
once every week for 3 doses.
9.2.
Risks Associated With BGB-DXP593
A FIH study of BGB-DXP593 is being tested in healthy subjects. A Phase 2 study of 
BGB-DXP593 in patients with mild to moderate COVID-19 will begin recruiting soon.
9.3.
General Plan to Manage Safety Concerns
9.3.1.
Eligibility Criteria
Eligibility criteria were selected to guard the safety of subjects in this study. Results from the 
nonclinical toxicology data from BGB-DXP604, BGB-DXP593, and nonclinical data from other 
SARS-CoV-2 neutralizing mAbs were considered. Subjects with any history of a severe allergic 
reaction that has a reasonable risk of recurrence are excluded from the study. Subjects with acute 
fever disease or infection are also excluded from the study (See Section 4.2 for the full list of 
exclusion criteria).
9.3.2.
Safety Monitoring Plan
Safety will be evaluated in this study through the monitoring of all AEs, defined and graded 
according to NCI-CTCAE v5.0. 
All enrolled subjects will be evaluated clinically and with standard laboratory tests at specified 
intervals during their participation in this study. Safety evaluations will consist of medical 
interviews, recording of AEs, physical examinations, laboratory measurements (hematology, 
clinical chemistry, etc), and other assessments including those listed in Appendix 1.
Blood samples will be drawn for determining of ADAs to BGB-DXP604 and BGB-DXP593 in 
subjects who received the study drug(s). Administration of the study drug(s) will be performed in 
a setting where emergency medical equipment and staff who are trained to respond to medical 
emergencies are available (Section 5.2).
As described in Section 9.7, AEs will be recorded during the study (AE from the time of 
administration of study drug(s) and SAEs from the time of signing of informed consent). At the 
end of study, AEs considered related to study drug(s) will be followed until the event has 
resolved to baseline or ≤Grade 1, the event is assessed by the investigator as stable, the subject 
is lost to follow-up, the subject withdraws consent, or it has been determined that study treatment 
or participation is not the cause of the AE.
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Investigators are instructed to report all AEs. The potential safety issues anticipated in this study, 
as well as measures intended to avoid or minimize such toxicities, are outlined in the following 
sections.
9.4.
Adverse Events
9.4.1.
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(s), whether considered related to study drug(s) or not.
Examples of an AE 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
New condition(s) detected or diagnosed after study drug(s) administration even 
though it may 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(s) or a concurrent medication. 
When an AE or SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory results, and diagnostics reports) relative to 
the AE or SAE. The investigator will then record all relevant information regarding an AE or 
SAE in the eCRF. However, there may be instances when copies of medical records for certain 
cases are requested by the sponsor. In these instances, all subject identifiers will be blinded on 
the copies of the medical records before submission to the sponsor.
9.4.2.
Assessment of Severity
The investigator will assess severity for each AE and SAE reported during the study. AEs and 
SAEs should be assessed and graded based upon the NCI-CTCAE v5.0.
Toxicities that are not specified in the NCI-CTCAE v5.0 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 (ADL) 
x
Grade 3: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL 
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 
(for example, grade of a specific AE, mild [Grade 1], moderate [Grade 2], severe [Grade 3], or 
life-threatening [Grade 4]), whereas seriousness is classified by the criteria based on the 
regulatory definitions. Seriousness serves as the guide for defining regulatory reporting 
obligations from the sponsor to applicable regulatory authorities as described in Section 9.7.2.1.
9.4.3.
Assessment of Causality
The investigator is obligated to assess the relationship between the study drug(s) 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(s) should be considered and investigated. The 
investigator should also consult the BGB-DXP604 Investigator’s Brochure and BGB-DXP593 
Investigator’s Brochure in the determination of his/her assessment.
There may be situations when a SAE has occurred, and the investigator has only limited
information to include in the initial report to the sponsor. However, it is very important that the 
investigator always assesses causality for every SAE 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.” An AE is considered related if there is “a reasonable possibility” that the AE may 
have been caused by the study drug(s) (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(s)
x
Biological plausibility
x
An AE should be considered “related” to study drug(s) if any of the following are 
met; otherwise the event should be assessed as “not related”:

There is clear evidence to suggest a causal relationship, and other possible 
contributing factors can be ruled out

There is evidence to suggest a causal relationship, and the influence of other 
factors is unlikely

There is some evidence to suggest a causal relationship (eg, the AE occurred 
within a reasonable time after administration of the study drug[s]). However, the 
influence of other factors may have contributed to the AE (eg, the subject’s 
clinical condition or other concomitant AEs).
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9.4.4.
Following Adverse Events and Serious Adverse Events
After the initial AE or SAE report, the investigator is required to proactively follow each subject 
and provide further information to the sponsor on the subject’s condition.
All AEs and SAEs documented at a previous visit/contact and designated as ongoing will be 
reviewed at subsequent visits/contacts.
All AEs and SAEs will be followed until resolution, the condition stabilizes or is considered 
chronic, the AE or SAE is otherwise explained, the subject is lost to follow-up, or the subject 
withdraws consent. The investigator will ensure that follow-up includes any supplemental 
investigations as may be indicated to elucidate the nature and/or causality of the AE or SAE. 
This may include additional laboratory tests or investigations, histopathological examinations, 
radiographic imaging, or consultation with other health care professionals.
The sponsor may request that the investigator perform or arrange for the conduct of supplemental 
measurements and/or evaluations to elucidate as fully as possible the nature and/or causality of 
the AE or SAE. The investigator is obligated to assist. If a subject dies during participation in the 
study or during a recognized follow-up period, the sponsor will be provided with a copy of any 
post-mortem findings, including histopathology.
New or updated information should be reported to the sponsor according to the SAE instructions 
provided to the site within the time frames outlined in Section 9.7.2.1.
9.4.5.
Laboratory Test Abnormalities
Abnormal laboratory findings (eg, clinical chemistry, complete blood count, coagulation, or 
urinalysis) or other abnormal assessments (eg, ECGs, cardiac telemetry, or vital signs) that are 
judged by the investigator as clinically significant will be recorded as AEs or SAEs. This 
includes clinically significant abnormal laboratory findings or other abnormal assessments that 
are present at baseline and significantly worsen during the study. The definition of clinically 
significant is left to the judgment of the investigator. In general, these are laboratory test 
abnormalities or other abnormal assessments that:
x
are associated with clinical signs or symptoms, or 
x
require active medical intervention, or 
x
lead to dose interruption or discontinuation, or
x
require close observation, more frequent follow-up assessments, or 
x
further diagnostic investigation.
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9.5.
Definition of a Serious Adverse Event
A 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 subject was at risk of death at the time of the AE. It does not refer to an 
AE, which hypothetically might have caused death if it were more severe.
x
Requires hospitalization or prolongation of existing hospitalization. 
NOTE: In general, hospitalization signifies that the subject was admitted (usually 
involving at least an overnight stay) to the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the physician’s 
office or outpatient setting. 
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 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 judgment 
(eg, may jeopardize the subject or may require medical/surgical intervention to 
prevent one of the outcomes listed above). 
The following are NOT considered SAEs:
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 
transfusion support or convenience.
9.6.
Suspected Unexpected Serious Adverse Reaction
A suspected unexpected serious adverse reaction (SUSAR) is a serious adverse reaction that is 
both unexpected (ie, not present in the product’s Reference Safety Information [RSI]) and meets 
the definition of a serious adverse drug reaction (SADR), the specificity or severity of which is 
not consistent with those noted in the BGB-DXP604 Investigator’s Brochure and BGB-DXP593 
Investigator’s Brochure.
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9.7.
Timing, Frequency, and Method of Capturing Adverse Events and 
Serious Adverse Events
9.7.1.
Adverse Event Reporting Period
After informed consent has been signed but before administration of the study drug(s), only 
SAEs should be reported.
After initiation of the study drug(s), all AEs and SAEs, regardless of relationship to study 
drug(s), will be reported until 30 days after the administration of study drug(s) or the EOS Visit,
whichever is later. After the period, the investigator should report any SAEs that are considered
to be related to the study drug(s).
9.7.2.
Reporting of Serious Adverse Events
9.7.2.1.
Prompt Reporting of Serious Adverse Events
As soon as the investigator determines that an AE meets the protocol definition of a SAE, the 
event must be reported promptly (within 24 hours) to the sponsor or designee as described in 
Table 5.
Table 5:
Timeframe and Documentation Methods for Reporting Serious Adverse 
Events to the Sponsor or Designee
Timeframe for 
Making Initial 
Report
Documentation 
Method
Timeframe for 
Sending
Follow-up Report
Documentation 
Method
Reporting 
Method
All 
SAEs
Within 24 hours of 
first knowledge of the 
SAE
SAE Report
As expeditiously 
as possible
SAE Report
Email or 
fax SAE 
report 
form
Abbreviations: SAE, serious adverse event.
9.7.2.2.
Completion and Transmission of the Serious Adverse Event Report
Once an investigator becomes aware that a SAE has occurred in a subject, he/she is to report the 
information to the sponsor within 24 hours as outlined in Section 9.7.2.1. The SAE report will 
always be completed as thoroughly as possible with all available details of the event and 
forwarded to the sponsor or designee within the designated time frames.  
If the investigator does not have all information regarding a SAE, he/she is not to wait to receive 
additional information before notifying the sponsor or designee of the SAE and completing the 
form. The form will be updated when additional information is received. 
The investigator must always provide an assessment of causality for each SAE as described in 
Section 9.4.3.
The sponsor will provide contact information for SAE receipt.
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9.7.2.3.
Regulatory Reporting Requirements for Serious Adverse Events
The investigator will promptly report all SAEs to the sponsor in accordance with the procedures 
detailed in Section 9.7.2.1. The sponsor has a legal responsibility to notify, as appropriate, both 
the local regulatory authority and other regulatory agencies about the safety of a product under 
clinical investigation. 
The investigator, or responsible person according to local requirements, will comply with the 
applicable local regulatory requirements related to the reporting of SAEs to regulatory authorities 
and the IRB/IEC.
All SUSARs (as defined in Section 9.6), will be submitted to all applicable regulatory authorities 
and investigators for BGB-DXP604 and 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.
9.7.3.
Eliciting Adverse Events
The investigator or designee will ask 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?
9.7.4.
Death
Death is an outcome and not usually considered an event. If the only information available is 
death and the cause of death is unknown, then the death is reported as an event (eg, “death,”
“death of unknown cause,” or “death unexplained.”)
9.7.5.
Recording Pregnancies
If the partner of a male subject becomes pregnant within 30 days after the administration of study 
drug(s), a pregnancy report form is required to be completed and expeditiously submitted to the 
sponsor to facilitate outcome follow-up. Information on the status of the mother and child will be 
forwarded to the sponsor. Generally, follow-up will be no longer than 6 to 8 weeks following the 
estimated delivery date. Any premature termination of the pregnancy will be reported.
While pregnancy itself is not considered to be an AE, any pregnancy complication or elective 
termination of a pregnancy for medical reasons will be recorded as an AE or SAE.
An abortion, whether accidental, therapeutic, or spontaneous should be always reported as a 
SAE. Similarly, any congenital anomaly/birth defect in a child born to a subject exposed to the 
study drug(s) should be recorded and reported as a SAE.
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9.7.6.
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 documents:
x
BGB-DXP604 Investigator’s Brochure
x
BGB-DXP593 Investigator’s Brochure
9.7.7.
Reporting Infusion-Related Reactions
The symptoms of infusion-related reactions may include, but are not limited to, fever, 
chills/rigor, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, 
vomiting, myalgia, dizziness, or hypertension. Severe reactions may include acute respiratory 
distress syndrome, myocardial infarction, ventricular fibrillation, or cardiogenic shock.
Individual signs and symptoms of an infusion reaction should be recorded each as a separate AE 
in the eCRF and identified as an infusion-related reaction. Refer to the eCRF completion 
guidelines for details.
9.8.
Management of Infusion-Related Reactions and Severe 
Hypersensitivity Reactions
As a routine precaution, following completion of the study drug(s) administration, subjects must 
be monitored for ≥2 hours after the infusion of study drug(s) in a setting where emergency 
medical equipment and staff who are trained to respond to medical emergencies are available.
The management of infusion-related reactions and severe hypersensitivity reactions according to 
the NCI-CTCAE criteria are outlined in the following subsections.
9.8.1.
Managing Infusion-Related Reactions
The symptoms of infusion-related reactions include fever, chills/rigor, nausea, pruritus, 
angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness,
or hypertension. Severe reactions may include acute respiratory distress syndrome, myocardial 
infarction, ventricular fibrillation, and cardiogenic shock.
Subjects should be closely monitored for infusion-related reactions. Immediate access to an 
Intensive Care Unit or equivalent environment and appropriate medical therapy (including 
epinephrine, corticosteroids, intravenous antihistamines, bronchodilators, and oxygen) must be 
available to treat infusion-related reactions.
Treatment modifications for symptoms of infusion-related reactions due to the study drug(s) are 
provided in Table 6.
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Table 6:
Treatment Modifications for Symptoms of Infusion-Related Reactions Due to 
Study Drug(s)
NCI-CTCAE grade
Treatment modification for Study Drug(s)
Grade 1 - mild
Mild transient reaction; infusion interruption not 
indicated; intervention not indicated.
Decrease infusion rate by 50%. Any worsening is 
closely monitored. Medical management as 
needed. 
Grade 2 - moderate
Therapy or infusion interruption indicated but 
responds promptly to symptomatic treatment 
(eg, antihistamines, nonsteroidal 
anti-inflammatory drugs, narcotics, intravenous 
fluids); prophylactic medications indicated for 
≤24 hours.
Stop infusion. Infusion may be resumed at 50% of 
previous rate once infusion-related reaction has 
resolved or decreased to Grade 1 in severity 
within 2 hours of the infusion interruption. The 
subject should be discontinued from study drug(s)
if the Grade 2 infusion-related reaction has not 
resolved or decreased over 2 hours of the infusion
interruption.
Any worsening is closely monitored. Proper 
medical management should be instituted as 
described below.  
Grade 3 – severe
Prolonged (eg, not rapidly responsive to 
symptomatic medication and/or brief interruption 
of infusion); recurrence of symptoms following 
initial improvement; hospitalization indicated for 
clinical sequelae.
Immediately stop the infusion. Proper medical 
management should be instituted as described 
below.
The subject should be withdrawn from study drug 
treatment.
Grade 4 – life-threatening
Life-threatening consequences; urgent 
intervention indicated.
Immediately stop the infusion. Proper medical 
management should be instituted as described 
below.
The subject should be withdrawn from study drug 
treatment.
Hospitalization is recommended.
Abbreviations: NCI-CTCAE, National Cancer Institute-Common Terminology Criteria for Adverse Events.
NCI-CTCAE Grade 1 or 2 infusion reaction: Proper medical management should be 
instituted, as indicated per the type of reaction. This includes, but is not limited to, an 
antihistamine (eg, diphenhydramine or equivalent), antipyretic (eg, paracetamol or equivalent), 
and, if considered indicated, oral or intravenous glucocorticoids, epinephrine, bronchodilators, 
and oxygen. 
NCI-CTCAE Grade 3 or 4 infusion reaction: Proper medical management should be instituted 
immediately, as indicated per type and severity of the reaction. This includes, but is not limited 
to, oral or intravenous antihistamines, antipyretics, glucocorticoids, epinephrine, bronchodilators, 
and oxygen.
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9.8.2.
Severe Hypersensitivity Reactions 
If hypersensitivity reaction occurs, the subject must be treated according to the best available 
medical practice as described in the complete guideline for emergency treatment of anaphylactic 
reactions according to the ANZCOR Guideline-First Aid Management of Anaphylaxis 
(Australian Resuscitation Council 2016). Subjects should be instructed to report any delayed 
reactions to the investigator immediately.
In the event of a systemic anaphylactic/anaphylactoid reaction, the infusion must be stopped 
immediately and the subject discontinued from the study. Systemic anaphylactic/anaphylactoid 
reactions typically manifest within minutes following administration of the drug/antigen and are 
characterized by respiratory distress; laryngeal edema; and/or intense bronchospasm; and are 
often followed by vascular collapse or shock without antecedent respiratory difficulty; cutaneous 
manifestations such as pruritus and urticaria with/without edema; and gastrointestinal 
manifestations such as nausea, vomiting, crampy abdominal pain, and diarrhea.
The subject will be administered epinephrine injection and dexamethasone infusion if 
hypersensitivity reaction is observed. The subject should then be placed on monitor immediately 
and an Intensive Care Unit should be alerted for possible transfer if needed.
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10.
STATISTICAL METHODS AND SAMPLE SIZE 
DETERMINATION
Details of the statistical analyses will be included in a separate Statistical Analysis Plan. 
10.1.
Statistical Analysis
10.1.1.
Randomization Method
As discussed in Section 7.4, subjects will be randomized using the IRT system for this study.
10.1.2.
Analysis Sets 
The Safety Analysis Set will include all subjects who received either study drug.
The PK Analysis Set will include all subjects who received either study drug and had any 
measurable concentration of study drug(s).
The ADA Analysis Set will include all subjects who received either study drug and for whom
both baseline ADA and ≥1 postbaseline ADA results are available.
10.1.3.
Subject Disposition
The number of subjects randomized, treated, and discontinued from study drug(s) and/or study 
will be counted. The primary reason for study drug(s) and/or study discontinuation will be 
summarized according to the categories in the eCRF.
Important protocol deviations will be summarized and listed by each category.
10.1.4.
Demographics and Other Baseline Characteristics
Demographic and other baseline characteristics will be summarized in the Safety Analysis Set 
using descriptive statistics. Summary statistics will be presented for continuous demographic and 
baseline characteristic variables by treatment group. The number (percentage) of subjects in each 
category will be presented for categorical variables by treatment group. Continuous variables 
include, but are not limited to, age, weight, height, and BMI. Categorical variables include, but
are not limited to, sex, race, and ethnicity.
10.1.5.
Prior and Concomitant Therapy
Concomitant medications will be coded using the World Health Organization Drug Dictionary 
drug codes and will be further coded to the appropriate Anatomical Therapeutic Chemical code 
indicating therapeutic classification. Prior and concomitant medications will be summarized by 
treatment group.
Prior medications will be defined as medications that started before the administration of study 
drug(s). Concomitant medications will be defined as medications that (1) started before the
administration of study drug(s) and were continuing at the time of the administration of study 
drug(s), or (2) started on or after the date of the administration of study drug(s) ≤30 days after 
the administration of study drug(s).
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10.2.
Efficacy Analyses
There is no efficacy analysis planned for this study.
10.3.
Safety Analyses
AEs, ECGs, vital signs, and laboratory data will be reviewed and summarized on an ongoing 
basis during the study to evaluate the safety of subjects. Descriptive statistics will be used to 
analyze all safety data.
10.3.1.
Extent of Exposure
The extent of each study drug exposure will be summarized descriptively for the study drug(s) 
administered by treatment group. The number (percentage) of subjects with dose interruption and 
infusion rate decreased will be summarized with the respective reasons by treatment group.
Subject data listings will be provided for all dosing records and for calculated summary statistics.
10.3.2.
Adverse Events
The AE verbatim descriptions (as recorded by the investigator on the eCRF) will be classified 
into standardized medical terminology using the Medical Dictionary for Regulatory Activities 
(MedDRA). AEs will be coded to MedDRA by the lowest level term, preferred term (PT), and 
primary system organ class (SOC).
A TEAE is defined as an AE that had an onset date or a worsening in severity from baseline on 
or after the administration of study drug(s) and ≤30 days after the administration of study
drug(s). Only those AEs that were treatment emergent will be included in summary tables.  
The incidence of TEAEs will be reported as the number (percentage) of subjects with TEAEs by 
SOC and PT. A subject will be counted only once by the highest severity grade according to 
NCI-CTCAE v5.0 within a SOC and PT, even if the subject experienced ≥1 TEAE within a 
specific SOC and PT. The number (percentage) of subjects with TEAEs will also be summarized 
by relationship to the study drug(s).
Treatment-related AEs include those events considered by the investigator to be related to study 
drug(s) or with missing assessment of the causal relationship. Treatment-emergent SAEs and 
treatment-related TEAEs will be summarized. All AEs, treatment-emergent or otherwise, will be 
presented in subject data listings.
10.3.3.
Laboratory Analyses
Clinical laboratory (clinical chemistry, hematology, coagulation, and urinalysis) values will be 
evaluated for each laboratory parameter as appropriate. Abnormal laboratory values will be 
flagged and identified as those outside (above or below) the normal range. Laboratory 
parameters and their changes from baseline will be summarized by visit and treatment group.
Changes from baseline will only be summarized for subjects with both baseline and postbaseline 
measurements.
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10.3.4.
Vital Signs
Descriptive statistics for vital sign parameters (systolic and diastolic blood pressure, pulse rate,
respiratory rate, and body temperature) and changes from baseline will be summarized by visit 
and treatment group.
10.3.5.
Electrocardiogram
Descriptive statistics for ECG parameters and changes from baseline will be summarized by visit 
and treatment group.
10.4.
Pharmacokinetic Analyses
Noncompartmental analyses will be carried out for BGB-DXP604 and BGB-DXP593 serum 
concentrations. The PK analyses will include only subjects with enough data to enable estimation 
of key parameters. 
Parameters, such as Cmax, tmax, t1/2, AUCt, AUCinf, AUC0-29, CL, and Vz (as appropriate for data 
collected), may be derived and summarized using 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 treatment 
group. 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 for BGB-DXP604 and BGB-DXP593 will be summarized using 
descriptive statistics by the number and percentage of subjects who develop detectable ADAs. 
The incidence of positive and neutralizing ADAs will be reported for evaluable subjects. The 
effect of immunogenicity on PK and safety may be evaluated if data allow.
10.6.
Sample Size Consideration
A sample size of 8 subjects for each cohort (6 active and 2 control) totaling ≤30 subjects 
(including possible replacement) is not based on any statistical considerations. The choice of 
sample size is based on clinical considerations to provide safety and tolerability information and 
pharmacological considerations with the need to minimize exposure to healthy subjects in each 
cohort. No formal inferential statistics will be applied to the safety or PK data.
10.7.
Interim Analysis
There is no formal interim analysis planned for this study.
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11.
STUDY COMMITTEE
11.1.
Safety Monitoring Committee
An SMC will be established and will include both the sponsor (including the medical monitor 
and study team members from Pharmacovigilance/Drug Safety, Clinical Pharmacology, and 
Biostatistics with other members as appropriate) and investigators. 
The SMC will review all available safety and laboratory data and make recommendations on 
dose escalations in Part 1 and the initiation of combination cohort in Part 2. The SMC may also 
be called upon by the sponsor on an ad hoc basis where applicable to the conduct of the study.
A separate charter will outline the details for the composition and responsibility of the SMC.
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12.
SOURCE DOCUMENTS AND ACCESS TO SOURCE 
DATA/DOCUMENTS
The investigator must maintain adequate and accurate records to ensure that the conduct of the
study may be fully documented. Such records include, but are not limited to, the protocol, 
protocol amendments, ICFs, and documentation of IRB/IEC and governmental approvals. In 
addition, at the end of the study, the investigator will receive subject data, which will include an 
audit trail containing a complete record of all changes to such data.
12.1.
Access to Information for Monitoring
In accordance with International Council for Harmonisation GCP guidelines, the study monitor 
must have direct access to the investigator’s source documentation to verify the data recorded in 
the eCRFs for consistency.
The monitor is responsible for routine review of the eCRFs at regular intervals throughout the 
study to verify adherence to the protocol and the completeness, consistency, and accuracy of the 
data being entered on them. The monitor should have access to any subject records needed to 
verify the entries in the eCRFs. The investigator agrees to cooperate with the monitor to ensure 
that any problems detected during these monitoring visits are resolved.
12.2.
Access to Information for Auditing or Inspections
Representatives of regulatory authorities or of BeiGene may conduct inspections or audits any 
time during or after completion of this clinical study. If the investigator is notified of an 
inspection by a regulatory authority, the investigator agrees to notify the sponsor or its designee 
immediately. The investigator agrees to provide to representatives of a regulatory agency or 
BeiGene access to records, facilities, and personnel for the effective conduct of any inspection or 
audit.
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13.
QUALITY ASSURANCE AND QUALITY CONTROL
13.1.
Regulatory Authority Approval
The sponsor will obtain approval to conduct the study from the appropriate regulatory agency in 
accordance with any applicable country-specific regulatory requirements or file the protocol to 
the appropriate regulatory agency before the study is initiated at a study center in that country.
13.2.
Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, the sponsor may 
conduct a quality assurance audit. Regulatory agencies may also conduct a regulatory inspection 
of this study. Such audits/inspections can occur at any time during or after completion of the 
study. If an audit or inspection occurs, the investigator and institution agree to allow the 
auditor/inspector direct access to all relevant documents and to allocate his/her time and the time 
of his/her personnel to the auditor/inspector to discuss findings and any relevant issues.
13.3.
Study Site Inspections
This study will be organized, performed, and reported in compliance with the protocol, standard 
operating procedures, working practice documents, and applicable regulations and guidelines. 
Site audits may be performed periodically by the sponsor’s or the contract research 
organization’s qualified compliance auditing team, which is an independent function from the 
study team responsible for conduct of the study.
Site visits will be conducted by the sponsor or an authorized representative to inspect study data, 
subjects’ medical records, and eCRFs. The investigator is to permit national and local health 
authorities; sponsor study monitors, representatives, and collaborators; and IRB/IEC members to 
inspect all facilities and records relevant to this study.
13.4.
Drug Accountability
The investigator or designee (ie, unblinded pharmacist[s]) 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), subject 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 subjects, including 
batch/lot number, date dispensed, subject identifier number, and the initials of the person 
dispensing the medication.
At study initiation, the monitor will evaluate the site’s standard operating procedure for study 
drug disposal/destruction to ensure that it complies with BeiGene requirements specified in the 
Pharmacy Manual. At appropriate times during the conduct of the study or at the end of the study 
following final drug inventory reconciliation by the monitor, the study site will dispose of and/or 
destroy all unused study drug supplies, including empty containers, according to these 
procedures. If the site cannot meet BeiGene’s requirements specified in the Pharmacy Manual 
for disposal, arrangements will be made between the site and BeiGene or its representative for 
destruction or return of unused study drug supplies.
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All drug supplies and associated documentation will be periodically reviewed and verified by the 
study monitor over the course of the study.
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14.
ETHICS/PROTECTION OF HUMAN SUBJECTS
14.1.
Ethical Standard
This study will be conducted by the principal investigator and the study center in full 
conformance with the International Council for Harmonisation E6 guideline for GCP and the 
principles of the Declaration of Helsinki or the laws and regulations of the country in which the 
research is conducted, whichever affords the greater protection to the subject. The study will also 
comply with the requirements of the International Council for Harmonisation E2A guideline 
(Clinical Safety Data Management: Definitions and Standards for Expedited Reporting).
14.2.
Institutional Review Board/Independent Ethics Committee
This protocol, the ICFs, any information to be given to the subject, and relevant supporting 
information must be submitted, reviewed, and approved by the IRB/IEC before the study is 
initiated. In addition, any subject recruitment materials must be approved by the IRB/IEC. 
Copies of the IEC/IRB correspondence and approval of the amended ICF/other information and 
the approved amended ICF/other information must be forwarded to the sponsor promptly.
The principal investigator is responsible for providing written summaries of the status of the 
study to the IRB/IEC annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/IEC. Investigators are also responsible for promptly 
informing the IRB/IEC of any protocol amendments. In addition to the requirements for 
reporting all AEs to the sponsor, investigators must comply with requirements for reporting 
SAEs to the local health authority and IRB/IEC. Investigators may receive written 
Investigational New Drug Safety Reports or other safety-related communications from the 
sponsor. Investigators are responsible for ensuring that such reports are reviewed and processed
in accordance with health authority requirements and the policies and procedures established by 
their IRB/IEC and archived in the site’s study file.
14.2.1.
Protocol Amendments
Any protocol amendments will be prepared by the sponsor. All protocol modifications must be 
submitted to competent authorities according to local requirements and to the IRB/IEC together 
with, if applicable, a revised model ICF in accordance with local requirements. Written 
documentation from competent authorities (according to local requirements) and from the 
IRB/IEC and required site approval must be obtained by the sponsor before changes can be 
implemented, except for changes necessary to eliminate an immediate hazard to subjects or 
changes that involve logistical or administrative aspects only (eg, change in medical monitor or 
contact information).
Information on any change in risk and/or change in scope must be provided to subjects already 
actively participating in the study, and they must read, understand, and sign each revised ICF 
confirming their willingness to remain in the study.
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14.3.
Informed Consent
The sponsor’s sample ICF will be provided to each site. If applicable, it will be provided in a 
certified translation of the local language. The final IRB/IEC-approved ICFs must be provided to
the sponsor for health authority submission purposes according to local requirements.
The ICFs must be signed and dated by the subject or the subject’s legally authorized 
representative before his or her participation in the study. The case history or clinical records for 
each subject shall document the informed consent process and that written informed consent was 
obtained before participation in the study.
The ICFs will be revised whenever there are changes to study procedures or when new 
information becomes available that may affect the willingness of the subject to participate. The 
final revised IRB/IEC-approved consent forms must be provided to the sponsor for health 
authority submission purposes.
Subjects must be re-consented to the most current version of the ICFs (or to a significant new 
information/findings addendum in accordance with applicable laws and IRB/IEC policy) during 
their participation in the study. For any updated or revised ICFs, the case history or clinical 
records for each subject shall document the informed consent process and that written informed 
consent was obtained using the updated/revised ICFs for continued participation in the study.
A copy of each signed ICF must be provided to the subject or the subject’s legally authorized
representative. All signed and dated ICFs must remain in each subject’s study file or in the site 
file and must be available for verification by study monitors at any time.
14.4.
Subject and Data Confidentiality
The principal investigator and sponsor will maintain confidentiality and privacy standards by 
following applicable data privacy laws covering the collection, storage, transmission, and 
processing of subjects’ personal and medical information.
The principal investigator shall code the medical information obtained during the study with a 
unique subject identification number assigned to each subject enrolled in the study. This 
approach ensures that subjects’ names are not included in any data set transmitted to any sponsor 
location.
Subject medical information obtained during this study is confidential and may only be disclosed 
to third parties as permitted by the signed ICF (or a separate authorization for the use and 
disclosure of personal health information that has been signed by the subject), unless permitted 
or required by law.
In the event of a breach of the confidentiality of a subject’s personal and medical information, 
the principal investigator and sponsor, as appropriate, shall fulfill all mediation steps and 
reporting obligations under applicable data privacy laws.
Medical information may be given to a subject’s personal physician or other appropriate medical 
personnel responsible for the subject’s welfare for treatment purposes.
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Data generated during this study must be available for inspection upon request by representatives 
of the Therapeutic Goods Administration in Australia and all other national and local health 
authorities; by sponsor monitors, representatives, and collaborators; and by the IRBs/IECs for 
each study site, as appropriate.
The investigator must ensure that subjects’ anonymity will be strictly maintained and that their 
identities are protected from unauthorized parties. The investigator agrees that all information 
received from the sponsor, including but not limited to the BGB-DXP604 Investigator’s 
Brochure, BGB-DXP593 Investigator’s Brochure, this protocol, eCRFs, the Investigational New 
Drugs, and any other study information, remain the sole and exclusive property of the sponsor 
during the conduct of the study and thereafter. This information is not to be disclosed to any third 
party (except employees or agents directly involved in the conduct of the study or as required by 
law) without prior written consent from the sponsor. The investigator further agrees to take all 
reasonable precautions to prevent the disclosure by any employee or agent of the study site to 
any third party or otherwise into the public domain.
If a written contract for the conduct of the study includes confidentiality provisions inconsistent 
with this section is executed, that contract’s provisions shall apply to the extent they are 
inconsistent with this section.
14.5.
Financial Disclosure
Investigators are required to provide the sponsor with sufficient accurate financial information in 
accordance with regulations to allow the sponsor to submit complete disclosure or certification to 
the absence of certain financial interest of the clinical investigators and/or disclose those 
financial interests, as required, to the appropriate health authorities. This is intended to ensure 
financial interests and arrangements of the clinical investigators with BeiGene that could affect 
reliability of data submitted to health authorities are identified and disclosed by the sponsor. 
Investigators are responsible for providing information about their financial interests before 
participation in the study and to update this information if any relevant changes occur during the 
study and for 1 year after completion of the study (ie, last subject, last visit).
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15.
DATA HANDLING AND RECORD KEEPING
15.1.
Data Collection and Management Responsibilities
15.1.1.
Data Entry in the Electronic Case Report Form
All study-related data collected or received by the investigator or study team shall be promptly 
entered into the eCRFs. In no event should the entry of the study data into the eCRF be later than 
what is stipulated in the site contract after the data is collected or received by the investigator or 
study team without prior communication with and approval by the sponsor.
15.1.2.
Data Collection
Data required by the protocol will be entered into an electronic data capture (EDC) system.
Data collection in the eCRF should follow the instructions described in the eCRF Completion 
Guidelines. The investigator has ultimate responsibility for the collection and reporting of all 
clinical data entered in the eCRF. The e-signature of the investigator or designee must be 
provided in the EDC system to attest to its accuracy, authenticity, and completeness.
Data contained in the eCRFs are the sole property of BeiGene and should not be made available 
in any form to third parties without written permission from BeiGene, except for authorized 
representatives of BeiGene or appropriate regulatory authorities.
15.1.3.
Data Management/Coding
All final subject data, both eCRF and external data (eg, laboratory data), collected according to 
the protocol will be stored by BeiGene at the end of the study.
Standard procedures (including following data review guidelines, computerized validation to 
produce queries, and maintenance of an audit file that includes all database modifications) will 
be followed to support accurate data collection. Data will be reviewed for outliers, logic, data 
inconsistencies, and completeness.
During the study, a study monitor or a clinical research associate will make site visits to review 
protocol compliance, compare eCRFs against individual subject’s medical records, and ensure 
that the study is being conducted according to pertinent regulatory requirements.
The eCRF entries will be verified with source documentation. The review of medical records 
will be performed in a manner to ensure that subject confidentiality is maintained. Checking the 
eCRFs for completeness, clarity, and cross-checking with source documents is required to 
monitor the progress of the study. Direct access to source data is also required for inspections 
and audits, and will be carried out with due consideration to data protection and medical 
confidentiality.
The AE verbatim descriptions (the investigator’s description from the eCRF) will be coded using 
MedDRA. AEs will be coded to MedDRA by the lowest level term, PT, and primary SOC. 
Concomitant medications will be coded using the World Health Organization Drug Dictionary. 
Concomitant diseases/medical history will be coded using MedDRA.
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15.2.
Study Records Retention
The investigator must maintain adequate and accurate records to enable the conduct of the study 
to be fully documented and the study data to be subsequently verified. These documents should 
be classified into ≥1 of the following 2 categories: 1) investigator’s study file and/or 2) subject 
clinical source documents.
The investigator’s study file will contain the protocol/amendments, eCRF and query forms, 
IRB/IEC and governmental approval with correspondence, ICFs, drug records, staff curriculum 
vitae and authorization forms, and other appropriate documents and correspondence.
Subject clinical source documents (usually defined by the project in advance to record key 
efficacy/safety parameters independent of the eCRFs) would include but not be limited to 
documents such as the following: subject hospital/clinic records, physician’s and nurse’s notes, 
appointment book, original laboratory reports, ECG, electroencephalogram, x-ray, pathology and 
special assessment reports, consultant letters, screening and enrollment logs, etc.
Following closure of the study, the investigator must maintain all study records in a safe and 
secure location. The records must be maintained to allow easy and timely retrieval, when needed 
(eg, audit or inspection), and, whenever feasible, to allow any subsequent review of data in 
conjunction with assessment of the facility, supporting systems, and personnel. Where permitted 
by local laws/regulations or institutional policy, some or all of these records can be maintained in 
a format other than hard copy (eg, microfiche, scanned, electronic); however, caution needs to be 
exercised before such action is taken. The investigator must ensure that all reproductions are 
legible, are a true and accurate copy of the original, and meet accessibility and retrieval 
standards, including regenerating a hard copy, if required. Furthermore, the investigator must 
ensure there is an acceptable backup of these reproductions and that an acceptable quality control 
process exists for making these reproductions.
The sponsor will inform the investigator of the time period for retaining these records to comply 
with all applicable regulatory requirements. The minimum retention time will meet the strictest 
standard applicable to that study center for the study, as dictated by any institutional 
requirements, local laws or regulations, or the sponsor’s standards/procedures; otherwise, the 
retention period will default to 15 years.
The investigator must notify the sponsor of any changes in the archival arrangements including 
but not limited to the following: archival at an off-site facility or transfer of ownership of or 
responsibility for the records in the event the investigator leaves the study center.
If the investigator cannot guarantee this archiving requirement at the study site for any or all of 
the documents, special arrangements must be made between the investigator and BeiGene to 
store these in sealed containers outside of the site so that they can be returned sealed to the 
investigator in case of a regulatory audit. When source documents are required for the continued 
care of the subject, appropriate copies should be made for storage outside of the site.
Biological samples at the conclusion of this study may be retained as outlined in the agreement 
with the CRO managing the biological samples, for the shorter of: a period of ≤10 years or as 
allowed by your IRB/IEC.
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15.3.
Protocol Deviations
The investigator is responsible for ensuring that the study is conducted in accordance with the 
procedures and evaluations described in this protocol. Investigators assert they will apply due 
diligence to avoid protocol deviations and shall report all protocol deviations to the sponsor.
The investigator is to document and explain any deviations from the approved protocol. The 
investigator must promptly report any major deviations that might impact subject safety and/or 
data integrity to the sponsor and to the IRB/IEC, in accordance with established IRB/IEC 
policies and procedures.
15.4.
Study Report and Publications
A clinical study report will be prepared and provided to the regulatory agency(ies). BeiGene will 
ensure that the report meets the standards set out in the International Council for Harmonisation 
Guideline for Structure and Content of Clinical Study Reports (ICH E3). An abbreviated report 
may be prepared in certain cases.
The results of this study will be published or presented at scientific meetings in a timely, 
objective, and clinically meaningful manner that is consistent with good science, industry and 
regulatory guidance, and the need to protect the intellectual property of the sponsor, regardless of 
the outcome of the study. The data generated in this clinical study are the exclusive property of 
the sponsor and are confidential. For a multicenter study, the first publication or disclosure of 
study results shall be a complete, joint multicenter publication, or disclosure coordinated by the 
sponsor. Thereafter, any secondary publications will reference the original publication(s). 
Authorship will be determined by mutual agreement and all authors must meet the criteria for 
authorship established by the International Committee of Medical Journal Editors Uniform 
Requirements for Manuscripts or stricter local criteria (International Committee of Medical 
Journal Editors 2016).
Each investigator agrees to submit all manuscripts, abstracts, posters, publications, and 
presentations (both oral and written) to the sponsor for review before submission or presentation 
in accordance with the clinical study agreement. This allows the sponsor to protect proprietary 
information, provide comments based on information from other studies that may not yet be 
available to the investigator, and ensure scientific and clinical accuracy. The details of the 
processes of producing and reviewing reports, manuscripts, and presentations based on the data 
from this study will be presented in the investigator’s clinical study agreement. Each investigator 
agrees that, in accordance with the terms of the clinical study agreement, a further delay of the 
publication/presentation may be requested by the sponsor to allow for patent filings and/or 
protection in advance of the publication/presentation.
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15.5.
Study and Study Center Closure
Upon completion of the study, the monitor will conduct the following activities in conjunction 
with the investigator or study center personnel, as appropriate:
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 subject’s medical records) are the sole property of the
sponsor and will be kept confidential by the investigator and other study center personnel. 
This information and data will not be used by the investigator or other study center personnel for 
any purpose other than conducting the study without the prior written consent of the sponsor.
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 
subject
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.
Australian Resuscitation Council. ANZCOR guideline 9.2.7-first aid management of 
anaphylaxis. https://resus.org.au/glossary/. Accessed 19 November 2020.
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.
BeiGene Investigator’s Brochure, BGB-DXP593. Edition 2.0, September 2020.
BeiGene Investigator’s Brochure, BGB-DXP604. Edition 1.0, November 2020.
Cao YL, Su B, Guo XH, et al. Potent neutralizing antibodies against SARS-CoV-2 identified by 
high-throughout single-cell sequencing of convalescent patients’ B cells. Cell. 2020;182:1-12.
Clinical Trials Facilitation Group (CTFG). Recommendations related to contraception and 
pregnancy testing in clinical trials. http://www.hma.eu/fileadmin/dateien/Human_Medicines/01
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf. Accessed 
19 November 2020.
Jean SS, Lee PI, Hsueh PR. Treatment options for COVID-19: The reality and challenges. J
Microbiol Immunol and 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.
International Committee of Medical Journal Editors. Recommendations for the conduct, 
reporting, editing, and publication of scholarly work in medical journals. http://www.icmje.org. 
Accessed 19 November 2020.
Mahmood I, Balian JD. The pharmacokinetic principals behind scaling from preclinical results to 
phase I protocols. Clin Pharmacokinet. 1999;36(1):1-11.
Pharmaceutical Inspection Co-Operation Scheme. Guide to good manufacturing practice for 
medicinal products annexes. https://picscheme.org/docview/1946. Accessed 19 November 2020.
Renn A, Fu Y, Hu X, et al. Fruitful neutralizing antibody pipeline brings hope to defeat 
SARS-Cov-2. Trends Pharmacol Sci. 2020;44(11):815-29.
Sullivan HC, Roback JD. Convalescent plasma: therapeutic hope or hopeless strategy in the 
SARS-COV-2 pandemic. Transfusion Medicine Reviews. 2020;34(3):145-150.
US Department of Health and Human Services Food and Drug Administration, CDER: 
Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult 
healthy volunteers. 2005.
World Health Organization (WHO). Novel-coronavirus-2019.
https://www.who.int/emergencies/diseases/novel-coronavirus-2019. Accessed 19 November 
2020.
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.
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Zhou P, Yang XL, Wang XG, et al. A pneumonia outbreak associated with a new coronavirus of 
probable bat origin. Nature. 2020;579:1-4.
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APPENDIX 1.
SCHEDULE OF ASSESSMENTS
Period
Screening
Admission
to Unit
Treatm
ent
Follow-up
Day
-28 to -1
-1
D1 a
D2
D3
D4
D5
D8
D
15
D
22
D
29
D
43
D
57
D
71
D
85
D113
/ EOS
b
Safety 
Follow-up
Visit c
Visit Window (day)
--
--
--
--
--
--
--
--
±
1
±
1
±
1
±
2
±
2
±
2
±
2
± 2
± 3
Informed consent d
X
Inclusion/exclusion 
criteria e
X
X
Demography/prior 
medications
X
Medical history
X
Randomization f
X
BGB-DXP604 single 
dose administration g
X
BGB-DXP593 single 
dose administration g
X
(Part 2
only)
Discharge
X
Safety Assessments
Vital signs/
height and weight h
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Complete physical 
examination i
X
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Period
Screening
Admission
to Unit
Treatm
ent
Follow-up
Day
-28 to -1
-1
D1 a
D2
D3
D4
D5
D8
D
15
D
22
D
29
D
43
D
57
D
71
D
85
D113
/ EOS
b
Safety 
Follow-up
Visit c
Visit Window (day)
--
--
--
--
--
--
--
--
±
1
±
1
±
1
±
2
±
2
±
2
±
2
± 2
± 3
Targeted 
physical examination i
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG j
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Cardiac Telemetry k
X
X
Prior/Concomitant 
medications review
X
Adverse event review l
X
Laboratory Assessments
Hematology m
X
X
X
X
X
X
X
X
X
X
X
X
X
Clinical chemistry m
X
X
X
X
X
X
X
X
X
X
X
X
X
Coagulation m
X
X
X
X
X
X
X
X
X
X
X
X
X
IgG to SARS-CoV-2
X
rRT-PCR test for 
COVID-19
(nasopharyngeal or 
oropharyngeal swab)
X
X
Urinalysis n
X
X
X
X
X
X
X
X
X
X
X
X
X
Alcohol/drugs screen o
X
X
PK and ADA blood 
sampling
See Appendix 2 and Appendix 3
Hepatitis B and 
C testing
X
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Period
Screening
Admission
to Unit
Treatm
ent
Follow-up
Day
-28 to -1
-1
D1 a
D2
D3
D4
D5
D8
D
15
D
22
D
29
D
43
D
57
D
71
D
85
D113
/ EOS
b
Safety 
Follow-up
Visit c
Visit Window (day)
--
--
--
--
--
--
--
--
±
1
±
1
±
1
±
2
±
2
±
2
±
2
± 2
± 3
Pregnancy test (if 
applicable) p
X
X
X
X
X
X
HIV test
X
Abbreviations: ADA, antidrug antibody; AEs, adverse events; COVID-19, Coronavirus Disease 2019; D, day; ECG, electrocardiogram; EOS, End-of-Study; 
HIV, human immunodeficiency virus; Ig, immunoglobulin; IRT, Interactive Response Technology; PK, pharmacokinetic; rRT-PCR, real-time reverse 
transcription-polymerase chain reaction; SAEs, serious adverse events; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.
a
The schedule of assessments for Day 1 under different timepoints are provided in Appendix 2.
b
The EOS Visit will be conducted within 7 days after a premature study discontinuation. The Day 113 Visit is the EOS Visit for subjects who complete all 
previously planned study visits.
c
The Safety Follow-up Visit is only for subjects who discontinue the study within 30 days after the dose of study drug. The Safety Follow-up Visit will be 
conducted on 30 days after the dose of the study drug (± 3 days). If the premature discontinuation from study occurs within 7 days before the timepoint of 
30 days after the dose of the study drug, the Safety Follow-up Visit could be combined with the EOS Visit as appropriate. 
d
The informed consent must be obtained before performing any study-specific procedures. Consent must be obtained using the current version of the form 
approved by the Independent Ethics Committee/Institutional Review Board.
e Follicle-stimulating hormone and estradiol assessments will be performed on female subjects who are < 55 years of age with no spontaneous menses for 
≥12 months to identify the status of no childbearing potential. Female subjects of no childbearing potential and female subjects of childbearing potential who 
are willing to use a highly effective method of birth control are eligible to participate.
f
Subjects will be randomized into either the active arm or control arm via IRT. Randomization will occur after the admission on Day -1 and before the dose of 
study drug on Day 1.
g
The dose will be based on the subject’s actual body weight 1 day before the administration of study drug(s) (Day -1). In Cohort 2A, BGB-DXP593 should be
administrated first and BGB-DXP604 should be administrated ≥30 minutes after the completion of BGB-DXP593 infusion.
h
Height and weight will be measured at screening, and weight will be measured again on Day -1. 
i
Complete physical examination includes evaluations of 1) head, eyes, ears, nose, and throat; 2) cardiovascular; 3) dermatological; 4) musculoskeletal; 
5) respiratory; 6) gastrointestinal; and 7) neurological systems. At subsequent visits (and as clinically indicated), limited, symptom-directed physical 
examinations will be performed.
j
At each timepoint, 3 consecutive 12-lead ECGs will be performed approximately 2 minutes apart and within a maximum of 10 minutes to calculate heart rate 
and measure QT and QTcF intervals.
k
The cardiac telemetry will be performed from approximately 1 hour predose to 24 hours post dosing.
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l
After informed consent has been signed but before administration of the study drug, only SAEs should be reported. After initiation of the study drug, all AEs 
and SAEs, regardless of relationship to study drug, will be reported until 30 days after the dose of study drug or EOS Visit, whichever is later. After the 
period, the investigator should report any SAEs that are considered to be related to the study drug.
m
Hematology, clinical chemistry, and coagulation will be evaluated by a local laboratory. The list of hematology, clinical chemistry, and coagulation 
parameters is provided in Appendix 4.
n
Collect sample for urine analysis as well as urine microscopy. The urine microscopy will be performed if the urinalysis parameter, such as leukocyte, is out of 
normal range.
o
During the screening, a urine sample will be collected for the screening of drugs; a breath test will be performed for the screening of alcohol.
p Pregnancy test will be performed for female subjects of childbearing potential during the study. The urine pregnancy test will be performed at the Screening 
Visit, and the next urine pregnancy test will be conducted after the admission on Day -1 and before the dose of study drug on Day 1. Female subjects of 
childbearing potential with negative results will be eligible to receive the study drug. Afterwards, urine pregnancy test will be performed. A serum pregnancy 
test must be performed if the urine pregnancy test is positive or equivocal.
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APPENDIX 2.
SCHEDULE OF ASSESSMENT FOR DAY 1
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APPENDIX 2A. SCHEDULE OF ASSESSMENTS FOR DAY 1 (Part 1)
Study Day
Day 1
Timepoint
Predose
Drug Administration
EOI
1 hour 
postdose
6 hours 
postdose
12 hours 
postdose
Time (T) relative to infusion 
(h:min)
T = minus
01:00 – 00:00
T = minus 
00:30 – 00:00
T = minus 
00:15 – 00:00
T = 00:00
T = 00:30 
– 01:00
T = 1:00 
– 1:30
T = 02:00
(± 15 min)
T = 07:00
(± 15 min)
T = 13:00 
(± 15 min)
BGB-DXP604 single dose 
administration
Start 
infusion
Stop 
infusion
Vital signs
X
X
X
X
Targeted physical examination
X
12-lead ECG
X
X
X
X
Cardiac telemetry a
X
Prior/Concomitant medications 
review a
X
Adverse event review a
X
PK blood sampling
X
X
X (± 2 h)
ADA sampling
X
Abbreviations: ADA, antidrug antibody; ECG, electrocardiogram; EOI, end of infusion; h, hour; min, minutes; PK, pharmacokinetics.
a.
Cardiac telemetry, prior/concomitant medications review, and adverse event review will be performed throughout the Day 1.
NOTE: The timepoints of predose are the time relative to the start of infusion whereas the timepoints of postdose are the time relative to the end of infusion.
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APPENDIX 2B.
SCHEDULE OF ASSESSMENTS FOR DAY 1 (Part 2)
Study Day
Day 1
Timepoint
Predose
Drug Administration
EOI
1 hour 
postdose
6 hours 
postdose
12 hours
postdose
Time (T) relative to
infusion (h:min)
T =
minus 
01:00 –
00:00
T =
minus 
00:30 –
00:00
T =
minus 
00:15 –
00:00
T = 00:00
T =
00:30 –
01:00
T =
1:00 –
1:30
T =
1:30
T =
2:00 –
2:30
T =
2:30 
–
3:00
T = 03:30
(± 15 min)
T = 08:30 
(± 15 min)
T = 14:30 
(± 15 min)
BGB-DXP593 single 
dose administration
Start 
infusion
Stop 
infusion
BGB-DXP604 single 
dose administration
Prepare 
infusion
Start 
infusion
Stop 
infusion
Vital signs
X
X
X
X
Targeted 
physical examination
X
12-lead ECG
X
X
X
X
Cardiac telemetry a
X
Prior/Concomitant 
medications review a
X
Adverse event review a
X
PK blood sampling 
(DXP604 and DXP593)
X
X
X (± 2 h)
ADA sampling 
(DXP604 and DXP593)
X
Abbreviations: ADA, antibody antidrug; ECG, electrocardiogram; EOI, end of infusion; h, hour; min, minutes; PK, pharmacokinetics.
a.
Cardiac telemetry, prior/concomitant medications review, and adverse event review will be performed throughout the Day 1.
NOTE: The timepoints of predose are the time relative to the start of infusion whereas the timepoints of postdose are the time relative to the end of infusion.
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APPENDIX 3.
PHARMACOKINETIC AND ANTIDRUG ANTIBODY BLOOD SAMPLING)
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APPENDIX 3A.
PHARMACOKINETIC AND ANTIDRUG ANTIBODY BLOOD SAMPLING (Part 1)
Study Day
D1
D2
D3
D4
D5
D8
D15
D22
D29
D43
D57
D71
D85
D113
/EOS
Hours post
infusion
0
(predose)
EOI
6
24
48
72
96
168
336
504
672
1008
1344
1680
2016
2688
Window Period
(hours)
-60 min to 
predose
Within 
30 min 
after EOI
± 2
± 6
± 6
± 6
± 6
± 6
± 24
± 24
± 24
± 48
± 48
± 48
± 48
± 48
PK blood 
sampling
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ADA sampling
X
X
X
X
X
X
Abbreviations: ADA, antidrug antibody; D, day; EOI, end of infusion; EOS, End-of-Study; min, minutes; PK, pharmacokinetic.
Note: Sample collection must be from the opposite arm that is used for study drug infusion. Refer to laboratory manual for detailed collection instructions.
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APPENDIX 3B.
PHARMACOKINETIC AND ANTIDRUG ANTIBODY BLOOD SAMPLING (Part 2)
Study Day
D1
D2
D3
D4
D5
D8
D15
D22
D29
D43
D57
D71
D85
D113
/EOS
Hours post 
infusion
0
(predose)
EOI b
6 b
24
48
72
96
168
336
504
672
1008
1344
1680
2016
2688
Window Period
(hours)
-60 min to 
predose a
Within
30 min 
after EOI 
of second 
infusion
± 2
± 6
± 6
± 6
± 6
± 6
± 24
± 24
± 24
± 48
± 48
± 48
± 48
± 48
PK blood 
sampling
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
ADA sampling
X
X
X
X
X
X
Abbreviations: ADA, antidrug antibody; D, day; EOI, end of infusion; EOS, End-of-Study; min, minutes; PK, pharmacokinetics.
a.
Predose PK and ADA samples for both BGB-DXP604 and BGB-DXP593 may be collected together before the first infusion.
b.
EOI and 6 hours PK samples for both BGB-DXP604 and BGB-DXP593 may be collected together.
Note: Sample collection must be from the opposite arm that is used for study drug infusion. Refer to laboratory manual for detailed collection instructions.
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APPENDIX 4.
CLINICAL LABORATORY ASSESSMENTS
Clinical chemistry
Hematology
Coagulation
Urinalysis a
Alkaline phosphatase
Alanine aminotransferase
Aspartate aminotransferase
Albumin
Total bilirubin
Direct bilirubin
Blood urea nitrogen or urea
Potassium
Sodium
Total calcium
Creatinine
Glucose
Lactate dehydrogenase
Total protein
Magnesium
Lipase
Amylase
Red blood cell count
Hematocrit
Hemoglobin
Platelet count
White blood cell count with 
differential (both absolute 
count and percentage)
x
Lymphocyte count
x
Neutrophils
x
Monocytes
x
Eosinophils
x
Basophils
Prothrombin time
Partial thromboplastin 
time or activated partial 
thromboplastin time
International 
normalized ratio
Specific gravity
pH
Glucose
Protein
Blood
Ketones
Bilirubin
Urobilinogen 
Nitrite
Leukocyte
Other Screening Tests
x
Follicle-stimulating hormone and estradiol (as needed for female subjects who are < 55 years of age with no 
spontaneous menses for ≥12 months to identify the status of no childbearing potential)
x
Urine (drugs screen [to include at minimum: amphetamines, barbiturates, benzodiazepines, cocaine, opiates, 
methamphetamines, methadone, methyl enedioxy methamphetamine, phencyclidine, and
tetrahydrocannabinol])
x
Breath test (alcohol screen)
x
Highly sensitive (serum/urine) human chorionic gonadotropin pregnancy test (as needed in female subjects of 
childbearing potential)
x
Serology:
-
HIV antibody
-
hepatitis B surface antigen, hepatitis B core antibody, hepatitis C virus antibody
-
IgG antibodies against SARS-CoV-2
x
Virology: nasopharyngeal or oropharyngeal swab for COVID-19 rRT-PCR test
The results of each test must be entered into the CRF.
Abbreviations: COVID-19, Coronavirus Disease 2019; CRF, case report form; HIV, human immunodeficiency 
virus; Ig, immunoglobin; pH, negative of the logarithm to base 10 of the activity of the (solvated) hydronium ion; 
rRT-PCR, real-time reverse transcription polymerase chain reaction; SARS-CoV-2, severe acute respiratory 
syndrome coronavirus 2.
a
The urine microscopy will be performed if the urinalysis parameter, such as leukocyte, is out of normal range.
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APPENDIX 5.
CONTRACEPTION GUIDELINES AND DEFINITIONS
OF “WOMEN OF CHILDBEARING POTENTIAL”, “NO
CHILDBEARING POTENTIAL”
Contraception Guidelines
The Clinical Trials Facilitation Group’s recommendations related to contraception and 
pregnancy testing in clinical trials include the use of highly effective forms of birth control 
(Clinical Trials Facilitation Group 2014). These methods include the following:
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 subject’s usual and preferred lifestyle. Periodic abstinence (eg, calendar, 
ovulation, symptothermal, or postovulation methods), declaration of abstinence for the 
duration of exposure to study drug(s), and withdrawal are not acceptable methods of 
contraception.
Of note, barrier contraception (including male and female condoms with or without spermicide) 
is not considered a highly effective method of contraception and if used, this method must be 
combined with another acceptable method listed above.
Definitions of “Women of Childbearing Potential,” “Women of No Childbearing Potential”
As defined in this protocol, “women of childbearing potential” are female subjects who are 
physiologically capable of becoming pregnant.
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Conversely, “women of no childbearing potential” are defined as female subjects meeting any of
the following criteria:
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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SAP_001.pdf: