A Phase I Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7565020 in Healthy Participants and in Participants With Chronic Hepatitis B Virus Infection
Phase: PHASE1
Conditions: Chronic Hepatitis B
Sponsor: Hoffmann-La Roche



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The information contained in this document, especially any unpublished data, is the property of 
F. Hoffmann-La Roche Ltd (or under its control) and therefore, is provided to you in confidence as 
an Investigator, potential Investigator, or consultant, for review by you, your staff, and an 
applicable Ethics Committee or Institutional Review Board. It is understood that this information 
will not be disclosed to others without written authorization from Roche except to the extent 
necessary to obtain informed consent from persons to whom the drug may be administered. 
 
RO7565020—F. Hoffmann-La Roche Ltd 
Protocol BP44118, Version 3 
PROTOCOL 
TITLE: 
A PHASE I STUDY TO INVESTIGATE SAFETY, 
TOLERABILITY, PHARMACOKINETICS, AND 
PHARMACODYNAMICS OF RO7565020 IN 
HEALTHY PARTICIPANTS AND IN 
PARTICIPANTS WITH CHRONIC HEPATITIS B 
VIRUS INFECTION 
PROTOCOL NUMBER: 
BP44118 
VERSION: 
3 
REGULATORY AGENCY 
IDENTIFIER NUMBERS: 
IND Number: 163100 
EU Trial Number: 2022-502579-46-00 
TEST PRODUCT: 
RO7565020 
SPONSOR: 
F. Hoffmann-La Roche Ltd 
DATE FINAL: 
Version 1: 21 December 2022 
DATE AMENDED 
Version 2: 24 March 2023 
Version 3: See electronic signature and date 
stamp on the final page of this document 

RO7565020—F. Hoffmann-La Roche Ltd 
2/Protocol BP44118, Version 3 
PROTOCOL ACCEPTANCE FORM 
TITLE: 
A PHASE I STUDY TO INVESTIGATE SAFETY, 
TOLERABILITY, PHARMACOKINETICS, AND 
PHARMACODYNAMICS OF RO7565020 IN 
HEALTHY PARTICIPANTS AND IN 
PARTICIPANTS WITH CHRONIC HEPATITIS B 
VIRUS INFECTION 
PROTOCOL NUMBER: 
BP44118 
VERSION NUMBER: 
3 
REGULATORY AGENCY 
IDENTIFIER NUMBERS: 
IND Number: 163100 
EU Trial Number: 2022-502579-46-00 
TEST PRODUCT: 
RO7565020 
SPONSOR: 
F. Hoffmann-La Roche Ltd 
 
I agree to conduct the study in accordance with the current protocol. 
 
 
 
Principal Investigator’s Name (print) 
 
 
 
 
 
Principal Investigator’s Signature 
 
Date 
 
 
Please keep the signed original form in your study files, and return a copy to your local 
Site Monitor. 

RO7565020—F. Hoffmann-La Roche Ltd 
3/Protocol BP44118, Version 3 
PROTOCOL AMENDMENT, VERSION 3 
RATIONALE 
Protocol BP44118 Version 2 has been amended with the following changes, along with a 
rationale for each change, are summarized below. 
 
Table 1 (Part 1a SoA) and Table 2 (Part 1b SoA) have been updated to remove 
hepatitis D virus (HDV) and hepatitis E virus (HEV) tests at screening. As a 
defective virus, HDV is always co-infected with hepatitis B virus (HBV), and subjects 
with HBV infection will be excluded from the healthy volunteer parts of this study 
(Parts 1a and 1b) by serology. In addition, Part 1 will only be conducted in New 
Zealand and Hong Kong, which are non-endemic areas for HEV. Section 5.1.2 
exclusion criterion #2 has been updated according.  
 
Section 5.4 (Screen Failures) has been updated to allow re-screening for 
participants who failed screening due to a transient illness (e.g., influenza or 
COVID-19 infection).  
 
Nucleos(t)ide analogues (NUCs) designation has been updated to authorized 
auxiliary medicinal products (AxMPs)/non-investigational medicinal products 
(NIMPs) in Section 6 (Treatments) and Appendix 6 (Investigational Medicinal 
Product and Non-Investigational Medicinal Product Designations), including 
tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), and entecavir 
(ETV). TDF, TAF, and ETV have been approved globally for the treatment of chronic 
hepatitis B (CHB) and are the current standard of care. In this study, NUCs will be 
used as background treatment for all virologically suppressed participants with CHB 
(i.e., all participants in Parts 2 and 3) and administered per local prescribing 
information. 
 
Appendix 4 (Clinical Laboratory Tests) has been updated to allow, in some cases, 
determination of study eligibility based on local laboratory results. 
 
Substantial new information appears in Book Antiqua italics. This amendment represents 
cumulative changes to the original protocol. 
 

RO7565020—F. Hoffmann-La Roche Ltd 
4/Protocol BP44118, Version 3 
 
TABLE OF CONTENTS 
PROTOCOL ACCEPTANCE FORM .................................................................... 2 
PROTOCOL AMENDMENT, VERSION 3 RATIONALE ....................................... 3 
1. 
PROTOCOL SUMMARY ................................................................. 9 
1.1 
Synopsis .................................................................................... 9 
1.2 
Schematic of Study Design ...................................................... 15 
1.3 
Schedule of Activities ............................................................... 16 
2. 
INTRODUCTION ........................................................................... 30 
2.1 
Study Rationale ....................................................................... 30 
2.2 
Background.............................................................................. 30 
2.2.1 
Background on Chronic Hepatitis B ......................................... 30 
2.2.2 
Currently Available Therapies .................................................. 31 
2.2.3 
Background on RO7565020 .................................................... 31 
2.3 
Benefit–Risk Assessment ........................................................ 32 
3. 
OBJECTIVES AND ENDPOINTS ................................................. 33 
4. 
STUDY DESIGN ........................................................................... 36 
4.1 
Overall Design ......................................................................... 36 
4.1.1 
Dose Escalation ....................................................................... 40 
4.1.1.1 
Dose-Escalation Decision Criteria ........................................... 40 
4.1.1.2 
Dose Decision Team ............................................................... 40 
4.1.1.3 
Stopping Rules Criteria ............................................................ 41 
4.1.1.3.1 
Cohort Stopping Rules ............................................................. 41 
4.1.1.3.2 
Individual Participant Stopping Rules ...................................... 42 
4.1.1.4 
Communication Strategy ......................................................... 42 
4.2 
Scientific Rationale for Study Design ....................................... 43 
4.2.1 
Rationale for Study Population ................................................ 43 
4.2.2 
Rationale for Control Group ..................................................... 43 
4.2.3 
Rationale for Biomarker Assessments ..................................... 44 
4.2.3.1 
HBV Dynamic Biomarkers ....................................................... 44 
4.2.3.2 
HBV Genotype ......................................................................... 45 
4.2.3.3 
HBV DNA Monitoring and Viral Resistance ............................. 45 

RO7565020—F. Hoffmann-La Roche Ltd 
5/Protocol BP44118, Version 3 
4.2.3.4 
Immunological Biomarkers....................................................... 46 
4.2.4 
Justification for Dose ............................................................... 47 
4.3 
Duration of Participation .......................................................... 47 
4.4 
End of Study Definition ............................................................ 49 
5. 
STUDY POPULATION .................................................................. 50 
5.1 
Inclusion Criteria and exclusion criteria for Part 1 (Healthy 
participants) ............................................................................. 50 
5.1.1 
Inclusion Criteria for Part 1 ...................................................... 50 
5.1.2 
Exclusion Criteria for Part 1 ..................................................... 51 
5.2 
Inclusion Criteria and exclusion criteria for Parts 2 and 3 
(Participants with CHB) ............................................................ 53 
5.2.2 
Exclusion Criteria for Parts 2 and 3 ......................................... 55 
5.3 
Lifestyle Considerations ........................................................... 57 
5.3.1 
Meals and Dietary Restrictions ................................................ 57 
5.3.2 
Caffeine, Alcohol, and Tobacco ............................................... 57 
5.3.3 
Activity ..................................................................................... 57 
5.4 
Screen Failures ........................................................................ 57 
5.5 
Recruitment Procedures .......................................................... 58 
6. 
TREATMENTS .............................................................................. 59 
6.1 
Treatments Administered ......................................................... 59 
6.2 
Preparation, Handling, Storage, AND Accountability ............... 60 
6.3 
Measures to Minimize Bias: Randomization and Blinding ....... 60 
6.3.1 
Method of Treatment Assignment ............................................ 60 
6.3.2 
Blinding .................................................................................... 61 
6.4 
Treatment Compliance ............................................................ 62 
6.5 
Concomitant Therapy .............................................................. 63 
6.5.1 
Concomitant Medications for Part 1 ......................................... 63 
6.5.1.1 
Permitted Therapy for Part 1.................................................... 63 
6.5.1.2 
Prohibited Therapy for Part 1 ................................................... 63 
6.5.2 
Concomitant Medications for Parts 2 and 3 ............................. 63 
6.5.2.1 
Permitted Therapy for Parts 2 and 3 ........................................ 63 
6.5.2.2 
Prohibited Therapy for Parts 2 and 3 ....................................... 64 
6.6 
Dose Modification and Temporary Interruption ........................ 64 

RO7565020—F. Hoffmann-La Roche Ltd 
6/Protocol BP44118, Version 3 
6.6.1 
Temporary Interruption ............................................................ 64 
6.7 
Treatment after the End of the Study ....................................... 65 
7. 
DISCONTINUATION OF STUDY, STUDY TREATMENT, AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL ................... 66 
7.1 
Discontinuation of Study Treatment ......................................... 66 
7.2 
Participant Discontinuation OR Withdrawal from the Study ..... 67 
7.3 
Lost to Follow-Up ..................................................................... 67 
8. 
STUDY ASSESSMENTS AND PROCEDURES ........................... 69 
8.1 
Efficacy Assessments .............................................................. 69 
8.2 
Safety Assessments ................................................................ 69 
8.2.1 
Physical Examinations ............................................................. 69 
8.2.2 
Vital Signs ................................................................................ 70 
8.2.3 
Electrocardiograms .................................................................. 70 
8.2.4 
Clinical Safety Laboratory Assessments .................................. 71 
8.2.5 
Medical History and Demographic Data .................................. 72 
8.3 
Adverse Events and Serious Adverse Events ......................... 72 
8.3.1 
Period and Frequency for Collecting Adverse Event and 
Serious Adverse Event Information ......................................... 73 
8.3.2 
Method of Detecting Adverse Events and Serious Adverse 
Events ...................................................................................... 74 
8.3.3 
Follow-Up of Adverse Events and Serious Adverse Events .... 74 
8.3.3.1 
Investigator Follow-Up ............................................................. 74 
8.3.3.2 
Sponsor Follow-Up .................................................................. 74 
8.3.4 
Regulatory Reporting Requirements for Serious Adverse 
Events ...................................................................................... 74 
8.3.4.1 
Emergency Medical Contacts .................................................. 75 
8.3.5 
Pregnancy................................................................................ 75 
8.3.6 
Adverse Events of Special Interest .......................................... 75 
8.3.7 
Management of Specific Adverse Events ................................ 76 
8.4 
Treatment of Overdose ............................................................ 79 
8.5 
Pharmacokinetics .................................................................... 80 
8.6 
Immunogenicity Assessments ................................................. 81 
8.7 
Pharmacodynamics and Biomarkers Analyses ........................ 81 
8.7.1 
HBV Biomarker Assessments .................................................. 81 

RO7565020—F. Hoffmann-La Roche Ltd 
7/Protocol BP44118, Version 3 
8.7.2 
HBV Genotype ......................................................................... 82 
8.7.3 
Viral Resistance Monitoring ..................................................... 82 
8.7.4 
Exploratory Immunology Biomarkers ....................................... 82 
8.7.5 
Genetic and Genomic Analyses ............................................... 83 
8.7.5.1 
Clinical Genotyping .................................................................. 83 
8.7.5.2 
Transcriptome Analysis ........................................................... 83 
8.8 
Pharmacodynamics and Biomarker Samples .......................... 83 
8.8.1 
Mandatory Samples ................................................................. 84 
8.8.1.1 
Blood Sampling ........................................................................ 84 
8.8.1.2 
Urine Sampling ........................................................................ 84 
8.9 
Samples for Research Biosample Repository.......................... 84 
8.9.1 
Overview of the Research Biosample Repository .................... 84 
8.9.2 
Sample Collection .................................................................... 85 
8.10 
Health Economics OR Medical Resource Utilization and 
Health Economics .................................................................... 85 
8.11 
Timing of Study Assessments .................................................. 86 
8.11.1 
Screening and Pre-treatment Assessments............................. 86 
8.11.2 
Assessments during Treatment ............................................... 86 
8.11.3 
Assessments at Study Completion/Early Termination Visit ..... 86 
8.11.4 
Follow-Up Assessments .......................................................... 86 
8.11.5 
Assessments at Unscheduled Visits ........................................ 87 
8.11.6 
Exceptional Measures during COVID-19 Pandemic ................ 87 
9. 
STATISTICAL CONSIDERATIONS .............................................. 88 
9.1 
Statistical Hypotheses ............................................................. 88 
9.2 
Sample Size Determination ..................................................... 88 
9.3 
Analysis Sets ........................................................................... 89 
9.4 
Statistical Analyses .................................................................. 89 
9.4.1 
Demographics and Baseline Characteristics ........................... 89 
9.4.2 
Safety Analyses ....................................................................... 90 
9.4.2.1 
ECG Data Analysis .................................................................. 91 
9.4.3 
Pharmacokinetic Analyses ....................................................... 91 
9.4.4 
Immunogenicity Analyses ........................................................ 92 
9.4.5 
Pharmacodynamic Analyses .................................................... 92 

RO7565020—F. Hoffmann-La Roche Ltd 
8/Protocol BP44118, Version 3 
9.4.6 
Pharmacokinetic/ Pharmacodynamic Relationships ................ 93 
9.4.7 
Other Analyses ........................................................................ 93 
9.5 
Summaries of Conduct of Study .............................................. 94 
10. 
REFERENCES.............................................................................. 95 
11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ...................................................................... 98 
 
 
LIST OF TABLES 
Table 1 
Schedule of Activities – Part 1a .................................................. 17 
Table 2 
Schedule of Activities – Part 1b .................................................. 19 
Table 3 
Schedule of Activities – Part 2 .................................................... 23 
Table 4 
Schedule of Activities – Part 3 .................................................... 26 
Table 5 
Objectives and Endpoints ........................................................... 33 
Table 6 
Provisional Dose Regimens in Each Study Cohort ..................... 39 
Table 7 
Duration of Study Periods ........................................................... 48 
Table 8 
Summary of Treatments Administered ........................................ 59 
Table 9 
Guidelines for Managing Specific Adverse Events ...................... 77 
Table 10 
Analysis Sets .............................................................................. 89 
Table 11 
Safety Statistical Analysis Methods ............................................ 90 
Table 12 
Viral Dynamic Response Statistical Analysis Methods ............... 93 
Table 13 
Exploratory Viral Dynamic Response Statistical Analysis 
Methods ...................................................................................... 93 
 
 
LIST OF FIGURES 
Figure 1 
Overview of Study Design ........................................................... 15 
 
 
LIST OF APPENDICES 
Appendix 1 
Regulatory, Ethical, and Study Oversight Considerations ........... 99 
Appendix 2 
Adverse Events: Definitions and Procedures for Evaluating, 
Follow-up and Reporting ........................................................... 109 
Appendix 3 
Procedures for Recording Adverse Events ............................... 116 
Appendix 4 
Clinical Laboratory Tests .......................................................... 121 
Appendix 5 
Contraceptive and Barrier Methods Guidance .......................... 124 
Appendix 6 
Investigational Medicinal Product and Non-Investigational 
Medicinal Product Designations ................................................ 129 
Appendix 7 
Abbreviations ............................................................................ 130 

 
RO7565020—F. Hoffmann-La Roche Ltd 
9/Protocol BP44118, Version 3 
1. 
PROTOCOL SUMMARY 
1.1 
 SYNOPSIS 
PROTOCOL TITLE: 
A PHASE I STUDY TO INVESTIGATE SAFETY, TOLERABILITY, 
PHARMACOKINETICS, AND PHARMACODYNAMICS OF 
RO7565020 IN HEALTHY PARTICIPANTS AND IN PARTICIPANTS 
WITH CHRONIC HEPATITIS B VIRUS INFECTION 
SHORT TITLE 
RO7565020 Phase I Study in healthy participants and 
participants with chronic hepatitis B 
PROTOCOL NUMBER: 
BP44118 
VERSION: 
3 
REGULATORY 
AGENCY IDENTIFIER 
NUMBERS: 
IND Number: 163100 
EU Trial Number: 2022-502579-46-00 
TEST PRODUCT: 
RO7565020 
PHASE: 
I 
 
RATIONALE 
Chronic hepatitis B (CHB) virus infection is a major global healthcare problem, with an 
estimated prevalence of 296 million people. The current standard of care is either a possibly 
lifelong treatment with nucleos(t)ide analogues (NUCs) or interferon (IFN)-α preparations that, 
despite their poor safety and tolerability, provide in rare cases (~3%) a functional cure for 
patients (defined as the sustained loss of serum hepatitis B surface antigen [HBsAg] and 
hepatitis B virus [HBV] DNA). 
RO7565020 is a human origin monoclonal antibody (mAb) being developed for the treatment of 
CHB. RO7565020 binds the antigenic loop present in all forms of HBsAg and, as a potent 
HBsAg depleting agent, offers a potential to increase the functional cure rate or shorten the 
duration of treatment when given in combination with a direct acting antiviral and/or an 
immunomodulator for patients with CHB. 
This first-in-human (FIH), multi-center, dose-escalation Phase I clinical study of RO7565020 is 
aiming to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and 
preliminary antiviral responses following single and/or multiple doses of RO7565020 via SC 
injection and/or IV infusion in healthy participants and in virologically suppressed participants 
with CHB. 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
10/Protocol BP44118, Version 3 
OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary 
 
To assess the safety and tolerability 
o 
following a single dose of 
RO7565020 administered 
subcutaneously (SC) or 
intravenously (IV) to healthy 
participants (Part 1a) and SC to 
virologically suppressed participants 
with chronic hepatitis B (CHB) 
(Part 2) 
o 
following multiple doses of 
RO7565020 administered SC to 
healthy participants (Part 1b) and 
virologically suppressed participants 
with CHB (Part 3) 
 
Frequency and severity of adverse 
events (AEs), including adverse events 
of special interest (AESI), serious 
adverse events (SAE), and treatment 
discontinuations due to AEs 
 
Frequency of abnormal laboratory 
findings based on hematology, blood 
chemistry (including liver function tests), 
coagulation and urinalysis test results 
 
Frequency of clinically significant 
abnormalities in ECGs and vital signs 
 
Mean changes from baseline in vital 
signs (temperature, systolic and diastolic 
blood pressure, pulse rate, respiratory 
rate) over time 
Secondary 
 
To investigate the serum PK of 
RO7565020 
o 
following single-ascending doses of 
RO7565020 administered SC or IV 
to healthy participants (Part 1a) and 
SC to virologically suppressed 
participants with CHB (Part 2) 
o 
following multiple doses of 
RO7565020 administered SC to 
healthy participants (Part 1b) and 
virologically suppressed participants 
with CHB (Part 3) 
 
PK parameters of RO7565020 
o 
Time to maximum concentration 
(tmax) 
o 
Maximum serum concentration 
observed (Cmax) 
o 
AUC from Time 0 to time of last 
sampling point or last quantifiable 
sample, whichever comes first 
(AUC0-last) 
o 
AUC from Time 0 to infinity (AUCinf) 
o 
Terminal half-life (t1/2) 
o 
Volume of distribution (Vss) and 
clearance (CL) (IV only) 
o 
Apparent clearance (CL/F), 
apparent volume of distribution at 
terminal phase (Vz/F) (SC only) 

 
RO7565020—F. Hoffmann-La Roche Ltd 
11/Protocol BP44118, Version 3 
Objectives 
Endpoints 
Secondary (cont.) 
 
 
To characterize the antiviral response 
after a single dose or multiple doses of 
RO7565020 in virologically suppressed 
participants with CHB (Parts 2 and 3, 
respectively) 
 
Change from baseline in serum 
quantitative HBsAg 
 
Maximum reduction from baseline of 
serum HBsAg across all timepoints 
 
Proportion of participants with HBsAg 
loss (on quantitative and qualitative 
HBsAg assays) 
 
Proportion of participants with HBsAg 
seroconversion (sustained loss of 
HBsAg and detection of anti-HBs 
antibody) 
 
Proportion of participants with hepatitis 
B e antigen (HBeAg) loss among 
HBeAg-positive participants at baseline 
 
Proportion of participants with HBeAg 
seroconversion (sustained loss of 
HBeAg and detection of anti-HBe 
antibody) among HBeAg-positive 
participants at baseline 
 
To assess the immunogenicity (induction 
of anti-drug antibodies [ADA]) of 
RO7565020 in healthy participants and 
virologically suppressed participants with 
CHB 
 
ADA prevalence at baseline 
 
Incidence and titer of ADA over time 
 
OVERALL DESIGN AND STUDY POPULATION 
This FIH study of RO7565020 will be conducted in three parts: Part 1a is a Sponsor-open, 
Investigator-blinded, single-ascending dose (SAD) study in healthy participants with at least 
8 participants per cohort. Part 1b is an optional, Sponsor-open, Investigator-blinded multiple-
dose study with 8 healthy participants in 1 cohort. Part 2 is a SAD study in virologically 
suppressed participants with CHB with 6 participants in each cohort. Participants will be 
enrolled into Parts 2a and 2b on the basis of the screening HBsAg level (cutoff: 3000 IU/mL). 
Part 3 is an optional, multiple-dose study with 6 virologically suppressed participants with CHB 
per cohort. 
RO7565020 will be administered via SC injection in healthy participants and participants with 
CHB, and via IV infusion over 2 hours to healthy participants only. In Parts 1a and 1b, 
participants will be randomized 6:2 to receive RO7565020 or placebo. In Parts 2 and 3, all 
participants will receive RO7565020 and all participants will continue to receive NUC therapy 
throughout the study. Sentinel dosing will be applied to each cohort. The sentinel participants 
will be monitored for at least 72 hours to confirm safety.  
A Dose Decision Team (DDT) consisting of Sponsor members (collectively having expertise in 
clinical science, clinical pharmacology, pharmacodynamics, statistics, and clinical safety) and 
Investigators will review emerging study data and make recommendations regarding dose 
escalation and overall study conduct. The dose escalation may be stopped if stopping criteria 
are met. Additional dose cohorts that assess lower or repeat doses may be investigated, 
however, dose modifications of the RO7565020 doses of individual participants are not 
permitted during the study. 
Several key aspects of the study design and study population are summarized below. 

 
RO7565020—F. Hoffmann-La Roche Ltd 
12/Protocol BP44118, Version 3 
Parts 1a and 1b 
Phase: 
I 
Population Type: 
Heathy participants 
Control Method: 
Placebo 
Population Diagnosis or 
Condition: 
Not applicable 
Interventional 
Model: 
Sequential 
Population Age: 
1865 years 
Test Compound: 
RO7565020 
Site Distribution: 
Multi-center 
Active Comparator: Not applicable 
Study Intervention 
Assignment Method: 
Permuted block 
randomization 
Number of Arms: 
Up to 7 
Number of Participants 
to Be Enrolled: 
4856 
 
Parts 2 and 3 
Phase: 
I 
Population Type: 
Adult patient 
Control Method: 
Not applicable 
Population Diagnosis or 
Condition: 
virologically suppressed 
participants with chronic 
hepatitis B 
Interventional 
Model: 
Sequential 
Population Age: 
1865 years 
Test Compound: 
RO7565020 
Site Distribution: 
Multi-center 
Active Comparator: Not applicable 
Study Intervention 
Assignment Method: 
Centralized assignment  
Number of Arms: 
Up to 9 
Number of Participants 
to Be Enrolled: 
3054 
 
 
STUDY TREATMENT 
The investigational medicinal product (IMP) for this study is RO7565020, an HBsAg mAb and it 
will be administered at the study center under supervision of site staff. NUCs are background 
treatment and are classified as authorized auxiliary medicinal products 
(AxMPs)/non-investigational medicinal products (NIMPs).  
In Part 1a, four provisional escalating RO7565020 dose levels are planned to be administered 
sequentially to 6 different cohorts of participants. The anticipated ascending-dose scheme is 
70 mg SC, 230 mg SC, 360 mg SC, 360 mg IV, and 9001500 mg IV or matching placebo. 
Cohort 6 (ethnicity bridging cohort: 360 mg SC or matching placebo) may be conducted in 
parallel with Cohort 4 after the preliminary safety evaluation in Cohort 3 is completed and 
considered safe. 
In Part 1b (optional), one dose cohort (SC injection; RO7565020 or matching placebo) is 
planned and the dose level and dosing frequency will be determined by using emerging safety 
and PK data from Part 1a. 
In Part 2a, a single dose of 70 mg SC, 230 mg SC, and 360 mg SC will be administered and in 
Part 2b, a single dose of 70 mg SC (optional), 230 mg SC, 360 mg SC, and 720 mg SC 
(optional) may be administered. 
In Part 3 (optional), multiple doses will be administered and dose level and dosing frequency will 
be determined using Part 1 and Part 2 data. 
In Parts 2 and 3, all participants will continue to receive NUC therapy throughout the study. 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
13/Protocol BP44118, Version 3 
DURATION OF PARTICIPATION 
Duration of participation for each part of this study as follows: 
Study 
part 
Screening 
Treatment 
period 
In-clinic period 
End-of-study visit*** 
Part 1a 
Up to 28 days 
Day 1 
Day 1 to Day 4 
36 weeks after study treatment 
administration 
Part 1b 
Up to 28 days 
Up to 
169 days 
Day -1 to Day 4, 
and 1 day after each 
administration for 
the following doses, 
including optional 
overnight stay* 
36 weeks after the last study 
treatment administration 
Parts 2a 
and 2b 
Up to 56 days 
(Pregnancy 
testing and 
liver function 
up to 14 days) 
Day 1 
Day 1** to Day 4, 
including optional 
overnight stay* 
24 weeks after study treatment 
administration 
(If HBsAg does not return to 
baseline level at follow-up 
Week 24, will have additional 
follow-up visits until returns 
to < 0.1 log below baseline for 
two consecutive visits, or up to 
56 weeks postdose, whichever 
comes first.) 
Part 3 
Up to 56 days 
(Pregnancy 
testing and 
liver function 
up to 14 days) 
Up to 
337 days 
Day 1** to Day 4, 
and 1 day after each 
administration for 
the following doses, 
including optional 
overnight stay* 
24 weeks after last study 
treatment administration  
(If HBsAg does not return to 
baseline level at follow-up 
Week 24, will have additional 
follow-up visits until return 
to < 0.1 log below baseline for 
two consecutive visits, or up to 
56 weeks post the final dose, 
whichever comes first.) 
Abbreviation: ADA = anti-drug antibody; HBsAg = hepatitis B surface antigen; 
PK = pharmacokinetic. 
*  For Part 1b, all participants will stay at the clinic overnight on Day 1 after each dose. Optional 
overnight stay at the clinic on Day 2 and Day 3 after the first dose, i.e., on Day 2 and Day 3, 
participants can either stay at the clinic overnight or can be discharged after completion of the 
assessments and return the next morning for the subsequent assessments, at the 
Investigator’s discretion.  
For all cohorts in Part 2a and Cohorts 1 and 2 in Part 2b, all participants will stay at the clinic 
for at least 8 hours postdose for safety observation and sample collection. The overnight stay 
from Day 1 to Day 4 for sample collection and assessment is optional, at the Investigator’s 
discretion.  
For Cohorts 3 and 4 in Part 2b, all participants will stay at the clinic overnight on Day 1. The 
overnight stay on Day 2 and Day 3 for sample collection and assessment is optional, at the 
Investigator’s discretion.  
For Part 3, all participants will stay at the clinic for at least 8 hours post each dose for safety 
observation and sample collection. Optional overnight stay at the clinic on Day 1 after each 
dose, and Day 2 and Day 3 after the first dose. 

 
RO7565020—F. Hoffmann-La Roche Ltd 
14/Protocol BP44118, Version 3 
**  Participants can stay at clinic the night before Day 1 (i.e., Day 1) if site prefers due to logistic 
reasons. 
*** After completing the scheduled visits, an additional ADA and PK sample collection may be 
needed, depending on the emerging ADA data. 
 
CONCOMITANT MEDICATIONS 
Permitted Therapy 
Participants who use oral contraceptives, hormone-replacement therapy, or other maintenance 
therapy should continue their use. 
Paracetamol/Acetaminophen at doses of  2 g/day is permitted for use any time during the 
study. 
 
Prohibited Therapy 
Participants should avoid taking non-prescription drugs (including vitamins and dietary or herbal 
supplements) within 2 weeks or 5 half-lives (whichever is longer) before the start of study 
treatment until completion of the follow-up visit, unless, in the opinion of the Investigator and 
Sponsor, the medication will not interfere with the study. 
Vaccination is prohibited between 2 weeks before and 1 week after a dose of RO7565020. 
For Part 1, as a general rule, no other concomitant medication will be permitted, with the 
exception of medications to treat AEs, unless the rationale for exception is discussed and 
clearly documented between the Investigator and the Sponsor. 
For Parts 2 and 3, use of the following therapies is prohibited (with the exception of medications 
to treat AEs), unless otherwise specified below, or the rationale for exception is discussed and 
clearly documented between the Investigator and the Sponsor. 
 
Any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including 
systemic oral or inhaled corticosteroids, IFN or pegylated [PEG]-IFN) is prohibited at any 
time during the study and for at least 8 weeks prior to the first dose of study treatment. Eye 
drop-containing, topical, and infrequent inhaled corticosteroids are permissible up to 
4 weeks. 
 
Any systemic antiviral therapy other than NUC (with the exception of oral therapy for herpes 
simplex virus [HSV] I or HSV II) is prohibited at any time during the study. 
 
Participants should follow the NUC prescribing information with respect to concomitant 
medication use while taking the NUC. 

 
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1.3 
SCHEDULE OF ACTIVITIES 
The schedule of activities (SoA) provided in Table 1 for Part 1a (single-ascending dose 
[SAD] in healthy participants), in Table 2 for part 1b (multiple doses in healthy 
participants), in Table 3 for Part 2 (SAD in participants with chronic hepatitis B [CHB]), 
and in Table 4 for Part 3 (multiple doses in participants with CHB). 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
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Table 1 
Schedule of Activities – Part 1a 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
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Table 1 
Schedule of Activities – Part 1a (cont.) 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AMA = antimitochondrial antibody; ANA = antinuclear antibody; ASMA = anti-smooth 
muscle antibody; a-TPO = anti-thyroid peroxidase; CRP = C-reactive protein; ECG = electrocardiogram; ET = early termination; HAV = hepatitis 
A virus; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; IV = intravenous; PK = pharmacokinetic; 
SAE = serious adverse event; SC = subcutaneous. 
 
a. 
Weight and height will be collected during screening period and Day 1. Weight will be collected in the following visits except Day 2, Day 3, and 
Day 4. 
b. 
These assessments do not need to be repeated on Day 1, if screening tests sample collection performed within 7 days before dosing.  
c. 
For the SC Cohorts (i.e., Cohorts 1, 2, 3, and 6), vital sign assessments will be performed at predose, 1 hour postdose, and 4 hours postdose 
on Day 1. For the IV Cohorts (i.e., Cohorts 4 and 5), vital sign assessments will be performed at predose, at the end of infusion, 1 hour after 
infusion completion, and 4 hours after infusion completion on Day 1. In addition, vital signs will be assessed every 30 minutes during infusion 
in the IV cohorts to support the evaluation of infusion-related reaction and these vital signs during infusion are not required to be captured in 
the electronic data capture (EDC) system unless abnormalities are observed. 
d. 
For all women enrolled in the study, blood sample for determining β-human chorionic gonadotropin (HCG) at Screening. Urine pregnancy tests 
will be performed at specified subsequent visits. If a urine pregnancy test is positive, it must be confirmed by a blood pregnancy test. 
Pregnancy testing will also be performed whenever a menstrual cycle is missed or when pregnancy is otherwise suspected and according to 
local practice. 
e. 
Unscheduled PK sample may be collected according to Section 8.2.3 and Section 8.5, e.g., at the time of treatment discontinuation if an 
infusion-related AE (such as an infusion- or injection-related reaction [IRR]) is reported, or when clinical significant abnormal ECG, an SAE, a 
severe AE, an AE leading to dose interruption or delay of RO7565020 administration, or an accidental overdose is reported. 
f. 
After participants complete the scheduled visits, an additional ADA and PK sample may be collected depending on the emerging ADA data. 
g. 
PK samples will be collected at predose (within 2 hours prior to drug administration), and 1 hour ( 5 minutes), 4 hours ( 15 minutes), and 
8 hours ( 30 minutes) postdose on Day 1. 
h. 
PK samples will be collected at predose (within 2 hours prior to drug administration), 5 minutes ( 1 minute) after the start of infusion, end of 
infusion ( 5 minutes), and 4 hours ( 15 minutes) and 8 hours ( 30 minutes) after infusion completes on Day 1. PK samples at 5 minutes 
after the start of infusion and at the end of infusion on the day of IV administration of RO7565020 MUST NOT be taken from the same arm as 
that used for study treatment administration. In the case of a participant being unable to provide venous access on the opposite arm to that 
used for study treatment administration, the leg may be used for PK blood sampling. 
i. 
Samples will be collected at predose. 
j. 
Samples will be collected at predose, and 4 hours and 8 hours postdose. 
 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
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Table 2 
Schedule of Activities – Part 1b 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
20/Protocol BP44118, Version 3 
Table 2 
Schedule of Activities – Part 1b (cont.) 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
21/Protocol BP44118, Version 3 
Table 2 
Schedule of Activities – Part 1b (cont.) 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AMA = antimitochondrial antibody; ANA = antinuclear antibody; ASMA = anti-smooth 
muscle antibody; a-TPO = anti-thyroid peroxidase; CRP = C-reactive protein; ECG = electrocardiogram; ET = early termination; HAV = hepatitis 
A virus; HBV = hepatitis B virus; HCV = hepatitis C virus; HIV = human immunodeficiency virus; PK = pharmacokinetic; SAE = serious adverse 
event. 
 
a. 
A period refers to the time between one dose of treatment and the start of the next. Up to 6 periods in total. 
b. 
Day 1 refers to the first day of each treatment period. Study day will be calculated on the basis of dosing frequency, e.g., if the dosing 
frequency is every 28 days, Day 1 of the 2nd treatment period will be Day 29 of the study; If the dosing frequency is every 56 days, Day 1 of 
the 2nd treatment period will be Day 57 of the study; If the dosing frequency is every 84 days, Day 1 of the 2nd period will be Day 85 of the 
study. From the second treatment period, for sentinel participants, the whole period can be advanced or delayed by 1 day (i.e., an 
additional  1 day visit window); for non-sentinel participants, the whole period can be advanced by 1 day or delayed by 3 days (i.e., an 
additional -1/+3 days visit window). 
c. 
Dose frequency will be determined by emerging Part 1a data. Some of these visits will not be needed depending on dose frequency, e.g., if 
the dose frequency is every 28 days, Day 29 and Day 57 visits will not be needed; if the dose frequency is every 56 days, Day 57 visit will not 
be needed. 
d. 
Weight and height will be collected during screening period and Day 1. Weight will be collected in the following visits except Day 2, Day 3, and 
Day 4. 
e. 
These assessments do not need to be repeated on Day 1, if screening tests sample collection performed within 7 days before dosing. 
f. 
Assessment and sample collection will be performed at predose. 
g. 
Vital signs assessments on dosing days: predose, 1 hour postdose, and 4 hours postdose. 
h. 
This assessment will be needed for Day 1 of some intermediate treatment periods only, depending on dose frequency. The minimum testing 
frequency of this assessment during treatment period is every 12 weeks. Thus, e.g., if the dose frequency is every 28 days, this assessment 
will be needed for Day 1 of the 4th treatment period only; if the dose frequency is every 56 days or every 84 days, this assessment will be 
needed for Day 1 of every intermediate treatment period. 
i.  
For all women enrolled in the study, blood sample for determining β-human chorionic gonadotropin (HCG) at Screening. Urine pregnancy tests 
will be performed at specified subsequent visits. If a urine pregnancy test is positive, it must be confirmed by a blood pregnancy test. 
Pregnancy testing will also be performed whenever a menstrual cycle is missed or when pregnancy is otherwise suspected and according to 
local practice. 
j. 
This assessment will be needed for Day 1 of some intermediate treatment periods only, depending on dose frequency. The minimum testing 
frequency of this assessment during treatment period is every 8 weeks. Thus, e.g., if the dose frequency is every 28 days, this assessment will 
be needed for Day 1 of the 3rd and the 5th treatment period; if the dose frequency is every 56 days or every 84 days, this assessment will be 
needed for Day 1 of every intermediate treatment period. 

 
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Table 2 
Schedule of Activities – Part 1b (cont.) 
k. 
All participants will stay at the clinic overnight on Day 1 after each dose. Optional overnight stay at the clinic on Day 2 and Day 3 in the first 
treatment period: participants can either stay at the clinic overnight or can be discharged after completion of the postdose assessments and 
return the next morning for the subsequent assessments, at the Investigator’s discretion. 
l. 
Unscheduled PK sample may be collected according to Section 8.2.3 and Section 8.5, e.g., at the time of treatment discontinuation if an 
infusion-related AE (such as an injection-related reaction) is reported, or when clinical significant abnormal ECG, an SAE, a severe AE, an AE 
leading to dose interruption or delay of RO7565020 administration, or an accidental overdose is reported. 
m. After participants complete the scheduled visits, an additional ADA and PK sample may be collected depending on the emerging ADA data. 
n. 
PK samples will be collected at predose (within 2 hours prior to drug administration), then 1 hour ( 5 minutes), 4 hours ( 15 minutes), and 
8 hours ( 30 minutes) postdose on Day 1 of the first and the last treatment periods. 
o. 
Samples will be collected at predose, then 4 hours and 8 hours postdose on Day 1 of the first and the last treatment periods. 
 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
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Table 3 
Schedule of Activities – Part 2 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
24/Protocol BP44118, Version 3 
Table 3 
Schedule of Activities – Part 2 (cont.) 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AFP = -fetoprotein; AMA = antimitochondrial antibody; ANA = antinuclear antibody; 
ARFI = elastography/acoustic radiation force impulse; ASMA = anti-smooth muscle antibody; a-TPO = anti-thyroid peroxidase; CRP = C-reactive 
protein; ECG = electrocardiogram; ET = early termination; HAV = hepatitis A virus; HBcrAg = hepatitis B core-related antigen; HBeAg = hepatitis 
B e antigen; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; HCV = hepatitis C virus; 
HDV = hepatitis D virus; HEV = hepatitis E virus; HIV = human immunodeficiency virus; MRI = magnetic resonance imaging; 
NUC = nucleos(t)ide analogue; PBMC = peripheral blood mononuclear cell; PK = pharmacokinetic; RBR = research biosample repository; 
SAE = serious adverse event; scRNAseq = single-cell RNA sequencing. 
 
a. 
If HBsAg value does not return to baseline level on Day 169, participants will come to the clinic for additional follow-up visits every 56 days 
until HBsAg value returns to  0.1 log below baseline for two consecutive visits, or up to Day 393, whichever comes first.  
b. 
Weight and height will be collected during screening period. Weight will be collected in the following visits except Day 2, Day 3, and Day 4 
visits. 
c. 
Assessments or sample collection will be performed at predose. 
d. 
Unscheduled sample for complement activation and CRP will be collected for suspected immune complex mediated adverse events and other 
events following Section 8.3.7. 
e. 
Vital sign assessments on Days 1: predose, 1 hour postdose, and 4 hours postdose. 
f. 
Required for Day 337 visit only. 
g. 
For all women enrolled in the study, blood sample for determining -human chorionic gonadotropin (HCG) at Screening. Urine pregnancy tests 
will be performed at specified subsequent visits. If a urine pregnancy test is positive, it must be confirmed by a blood pregnancy test. 
Pregnancy testing will also be performed whenever a menstrual cycle is missed or when pregnancy is otherwise suspected and according to 
local practice. 
h. 
Samples will be collected at predose, then at 4 hours and 8 hours postdose. 
i. 
In the additional visits, viral resistance sample needs to be collected in the last visit only, i.e., if HBsAg value returns to  0.1 log below 
baseline, viral resistance sample needs to be collected in the next confirmation visit. 
j. 
Liver biopsy or transient elastography/ARFI/MRI results obtained within 6 months prior to study Day 1 are also acceptable. 
k. 
For all cohorts in Part 2a and Cohorts 1 and 2 in Part 2b, all participants will stay at the clinic for at least 8 hours postdose for safety 
observation and sample collection. The overnight stay until Day 4 for sample collection and assessment is optional, at the Investigator’s 
discretion. For Cohorts 3 and 4 of Part 2b, all participants will stay at the clinic overnight on Day 1. The overnight stay on Days 2 and 3 for 
sample collection and assessment is optional, at the Investigator’s discretion. 
l. 
Unscheduled PK sample may be collected according to Section 8.2.3 and Section 8.5, e.g., at the time of treatment discontinuation if an 
infusion-related AE (such as an injection-related reaction) is reported, or when clinical significant abnormal ECG, an SAE, a severe AE, an AE 
leading to dose interruption or delay of RO7565020 administration, or an accidental overdose is reported. 

 
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Table 3 
Schedule of Activities – Part 2 (cont.) 
m. After participants complete the scheduled visits, an additional ADA and PK sample may be collected depending on the emerging ADA data. 
n. 
PK samples will be collected at predose (2 hours prior to drug administration), then 1 hour ( 5 minutes), 4 hours ( 15 minutes), and 
8 hours ( 30 minutes) postdose. 
o. 
Samples for these tests do not need to be collected if the participant has completed 169 days of follow-up. 
p. 
Only for participants from selected sites that decide to participate in PBMC collection. 
q. 
RBR samples will be collected only from participants who consent to RBR. 
 
 

 
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Table 4 
Schedule of Activities – Part 3 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
27/Protocol BP44118, Version 3 
Table 4 
Schedule of Activities – Part 3 (cont.) 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
28/Protocol BP44118, Version 3 
Table 4 
Schedule of Activities – Part 3 (cont.) 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; AFP = -fetoprotein; AMA = antimitochondrial antibody; ANA = antinuclear antibody; 
ARFI = elastography/acoustic radiation force impulse; ASMA = anti-smooth muscle antibody; a-TPO = anti-thyroid peroxidase; CRP = C-reactive 
protein; ECG = electrocardiogram; ET = early termination; FU = follow-up; HAV = hepatitis A virus; HBcrAg = hepatitis B core-related antigen; 
HBeAg = hepatitis B e antigen; HBsAb = hepatitis B surface antibody; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; 
HCV = hepatitis C virus; HDV = hepatitis D virus; HEV = hepatitis E virus; HIV = human immunodeficiency virus; MRI = magnetic resonance 
imaging; NUC = nucleos(t)ide analogue; PBMC = peripheral blood mononuclear cell; PK = pharmacokinetic; RBR = research biosample 
repository; SAE = serious adverse event; scRNAseq = single-cell RNA sequencing. 
 
a. 
A period refers to the time between one dose of treatment and the start of the next. Up to 6 periods in total. 
b. 
If HBsAg value does not return to baseline level on Day 169 of the last treatment period, participant needs to come to the clinic for additional 
follow-up visits every 56 days until HBsAg value returns to  0.1 log below baseline for two consecutive visits, or up to 56 weeks after final 
dose, whichever comes first. 
c. 
Day 1 refers to the first day of each treatment period. Study day will be calculated on the basis of dosing frequency, e.g., if the dosing 
frequency is every 28 days, Day 1 of the 2nd treatment period will be Day 29 of study; if the dosing frequency is every 56 days, Day 1 of the 
2nd treatment period will be Day 57 of study; if the dosing frequency is every 84 days, Day 1 of the 2nd period will be Day 85 of study. From 
the second period, for sentinel participants, the whole period can be advanced or delayed by 1 day (i.e., an additional 1 day visit window); for 
non-sentinel participants, the whole period can be advanced by 1 day or delayed by 3 days, (i.e., an additional -1/+3 days visit window). 
d. 
Dose frequency will be determined by emerging Parts 1 and 2 data. Some of these visits will not be needed depending on dose frequency, 
e.g., if the dose frequency is every 28 days, Day 29 and Day 57 visits will not be needed; if dose frequency is every 56 days, Day 57 visit will 
not be needed; if dose frequency is every 84 days, Day 29 and Day 57 visits will be needed.  
e. 
Weight and height will be collected during screening period. Weight will be collected in the following visits except Day 2, Day 3, and Day 4 
visits. 
f. 
Assessments and sample collection will be performed at predose. 
g. 
Unscheduled sample for complement activation and CRP will be collected for suspected immune complex mediated AEs and other events 
following Section 8.3.7. 
h. 
Vital sign assessments on dosing days: predose, 1 hour postdose, and 4 hours postdose. 
i. 
This assessment will be needed for Day 1 of some intermediate treatment periods only, depending on dose frequency. The minimum testing 
frequency of this assessment during treatment period is every 12 weeks. Thus, e.g., if the dose frequency is every 28 days, this assessment 
will be needed for Day 1 of the 4th treatment period; if the dose frequency is every 56 days or every 84 days, this assessment will be needed 
for Day 1 of every intermediate treatment period. 
j. 
Required for Day 337 of the last treatment period only. 

 
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Table 4 
Schedule of Activities – Part 3 (cont.) 
k. 
For all women enrolled in the study, blood sample for determining -human chorionic gonadotropin (HCG) at Screening. Urine pregnancy tests 
will be performed at specified subsequent visits. If a urine pregnancy test is positive, it must be confirmed by a blood pregnancy test. 
Pregnancy testing will also be performed whenever a menstrual cycle is missed or when pregnancy is otherwise suspected and according to 
local practice. 
l. 
This assessment will be needed for Day 1 of some intermediate treatment periods only, depending on dose frequency. The minimum testing 
frequency of this assessment during treatment period is every 8 weeks. Thus, e.g., if the dose frequency is every 28 days, this assessment is 
needed for Day 1 of the 3rd and the 5th treatment periods; if the dose frequency is every 56 days or every 84 days, this assessment is needed 
for Day 1 of every intermediate treatment period. 
m. This assessment will be needed for Day 1 of some intermediate treatment periods only, depending on dose frequency. The minimum testing 
frequency of this assessment during treatment period is every 24 weeks. Thus, e.g., if the dose frequency is every 28 days, this assessment 
will not be needed during the intermediate treatment periods; if the dose frequency is every 56 days, this assessment will be needed for Day 1 
of the 4th treatment period; if the dose frequency is every 84 days, this assessment will be needed for Day 1 of the 3rd treatment period. 
n. 
Samples will be collected at predose, then at 4 hours and 8 hours postdose on Day 1 of the first and the last treatment periods. 
o. 
The frequency of sample collection of these PD markers may be reduced depending on emerging data and dose frequency. 
p. 
In the additional visits, viral resistance sample needs to be collected in the last visit only, i.e., if the HBsAg value returns to  0.1 log below the 
baseline value, viral resistance sample needs to be collected in the next confirmation visit. 
q. 
Liver biopsy or transient elastography/ARFI/MRI results obtained within 6 months prior to study Day 1 are also acceptable. 
r. 
All participants will stay at the clinic for at least 8 hours post each dose for safety observation and sample collection. Overnight stay at the 
clinic on Day 1 after each dose, and on Days 2 and 3 after the first dose is optional. 
s. 
Participants can stay at site on the night before dosing if site prefers. 
t. 
Unscheduled PK sample may be collected according to Section 8.2.3 and Section 8.5, e.g., at the time of treatment discontinuation if an 
infusion-related AE (such as an injection-related reaction) is reported, or when clinical significant abnormal ECG, an SAE, a severe AE, an AE 
leading to dose interruption or delay of RO7565020 administration, or an accidental overdose is reported. 
u. 
After participants complete the scheduled visits, an additional ADA and PK sample may be collected depending on the emerging ADA data. 
v. 
PK samples will be collected at predose (2 hours prior to drug administration), then at 1 hour ( 5 minutes), 4 hours ( 15 minutes), and 
8 hours ( 30 minutes) postdose on Day 1 of the first and the last treatment periods. 
w. 
Samples for these tests do not need to be collected if the participant has completed 169 days of follow-up after the final dose. 
x. 
Only for participants from selected sites that decide to participate in PBMC collection. 
y. 
RBR samples will be collected only from participants who consent to RBR. 
 

 
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30/Protocol BP44118, Version 3 
2. 
INTRODUCTION 
2.1 
STUDY RATIONALE 
Chronic hepatitis B (CHB) virus infection is a major global healthcare problem, with an 
estimated prevalence of 296 million people (WHO 2022). The current standard of care is 
either a possibly lifelong treatment with nucleos(t)ide analogues (NUCs) or interferon 
(IFN)-  preparations that, despite their poor safety and tolerability, provide in rare cases 
(~3%) a functional cure for patients (defined as the sustained loss of serum hepatitis B 
surface antigen [HBsAg] and hepatitis B virus [HBV] DNA; Lok et al. 2017). 
RO7565020 is a human origin monoclonal antibody (mAb) being developed for the 
treatment of CHB. RO7565020 binds the "a-determinant" of the antigenic loop present in 
all forms of HBsAg and, as a potent HBsAg depleting agent, offers a potential to 
increase the functional cure rate or shorten the duration of treatment when given in 
combination with a direct acting antiviral and/or an immunomodulator for patients with 
CHB. 
This first-in-human (FIH), multi-center, dose-escalation Phase I clinical study of 
RO7565020 is aiming to investigate the safety, tolerability, pharmacokinetics, 
pharmacodynamics, and preliminary antiviral responses following single and/or multiple 
doses of RO7565020 via SC injection and/or IV infusion in healthy participants and in 
virologically suppressed participants with CHB. 
The scientific rationale for the study design is provided in Section 4.2. 
2.2 
BACKGROUND 
2.2.1 
Background on Chronic Hepatitis B 
HBV infection is a major cause of both acute hepatitis and chronic liver disease including 
cirrhosis and hepatocellular carcinoma (HCC). WHO estimates that 296 million people 
were living with CHB infection in 2019, with 1.5 million new infections each year. In 
2019, HBV infection resulted in an estimated 820,000 deaths, mostly from complications 
including cirrhosis and HCC (WHO 2022).  
Persistence of HBV infection is a consequence of the presence of covalently closed 
circular DNA (cccDNA) in the nuclei of infected hepatocytes. Despite the advancement 
in the understanding of HBV disease biology, eradication of cccDNA (defined as disease 
cure) is not likely in the near future. Nevertheless, the sustained clearance of HBsAg has 
been shown to be protective against disease progression and development of HBV 
complications including cirrhosis, liver failure, and HCC. Accordingly, current drug 
development efforts aim to achieve functional cure of CHB (i.e., sustained loss of HBsAg 
and HBV DNA) with finite treatment regimens (Lok et al. 2017). 

 
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2.2.2 
Currently Available Therapies 
Currently, there are two therapeutic classes available for the treatment of CHB: 
subcutaneously (SC) administered IFN preparations (conventional or pegylated [PEG]-
IFN-) and orally administered NUCs (tenofovir, entecavir, adefovir, telbivudine, and 
lamivudine). After 1 year of treatment, both types of treatment can suppress circulating 
HBV DNA levels (virologic response 7%94%), normalize serum liver transaminase 
enzymes (biochemical response 32%83%), and induce hepatitis B e antigen (HBeAg) 
seroconversion in HBeAg-positive patients (serological response 10%32%). Although 
these treatments reduce the risk of CHB sequelae, they are associated with very low 
rates of functional cure (HBsAg loss rates generally not exceeding 3% after 1 year of 
therapy) (European Association for the Study of the Liver [EASL] 2017). 
Furthermore, the existing standard-of-care therapies have important limitations. For 
example, virologic relapse after treatment discontinuation is a major limitation of 
currently approved therapies, which rarely result in functional cure. IFN-based therapies 
have common adverse events (AEs) of flu-like symptoms and can be associated with 
treatment-limiting adverse effects (e.g., neutropenia, thrombocytopenia), while NUCs 
require long-term and possibly lifelong therapy in the majority of treated patients. Given 
these limitations, there is an unmet need for novel treatments of a finite duration that 
yield higher functional cure rates (Liu et al. 2017; Durantel and Zoulim 2016; Lok et al. 
2017; Wang and Chen 2014). 
2.2.3 
Background on RO7565020 
RO7565020 is a human IgG1 mAb (anti-HBs neutralizing antibody Bc1.187) with a well 
characterized neonatal Fc receptor (FcRn) affinity-enhancing Fc mutation 
(M252Y/S254T/T256E; YTE) introduced to increase the half-life and enhance the 
pharmacokinetic (PK) properties. RO7565020 binds to the antigenic loop present in all 
forms of HBsAg (L-HBsAg, M-HBsAg, and S-HBsAg) and showed potent and cross-
reactive neutralization against genotypes A, B, C, and D in vitro. 
Sequential to a single dose of small interfering RNA (siRNA) surrogate, single dose 
RO7565020 treatment further reduced HBsAg level in the adeno-associated virus 
(AAV)-HBV mouse model from 3 log10 IU/mL to close to undetectable levels 
( 0.2 log10 IU/mL). 
In addition, RO7565020 can mediate phagocytic cell uptake of HBsAg particles, 
suggesting that antibody-coated viral particles and/or infected hepatocytes could be 
eliminated in vivo by phagocytes such as Kupffer cells. The Fc receptor-dependent 
function of antibody-dependent cellular phagocytosis (ADCP) may also facilitate antigen 
presentation to antigen-specific T cells, which could stimulate host humoral and cellular 
immune responses, a phenomenon known as the vaccine-like effect. 
A detailed description of the chemistry, pharmacology, nonclinical efficacy and safety of 
RO7565020 is provided in the RO7565020 IB. 

 
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2.3 
BENEFIT–RISK ASSESSMENT 
As this is the first-in-human study with RO7565020, no therapeutic benefit is anticipated 
for participants in Part 1 of this study (as for all early clinical studies in healthy 
participants) and no long-term benefit to participants with CHB is anticipated in Parts 2 
and 3 of this study. However, this study may benefit future patients, as it is essential for 
the development of new treatments for CHB, and for identifying the appropriate 
RO7565020 dose for study within a combination therapy setting. 
Given no prior clinical experience with RO7565020 exists, the evaluation of the potential 
risks of treatment and the specific tests, observations, and precautions required for 
clinical studies with RO7565020 is based primarily on available data from nonclinical 
toxicology and safety pharmacology studies, as well as information from clinical studies 
with other anti-HBsAg mAbs. Overall, the level of risk for the individual participants due 
to treatment with RO7565020 is considered to be minimal and will be managed in a 
stepwise manner.  
The main risk in healthy volunteers is related to the potential development of anti-drug 
antibody (ADA), while in participants with CHB there is an additional risk associated with 
target binding and the formation of HBsAg:HBsAb complexes. Risks will be mitigated by 
conservative selection of the starting dose, careful safety monitoring, staggered dose 
escalation, sentinel dosing, pre-specified stopping criteria, and well-defined participant 
characteristics and stopping criteria. 
No effect is anticipated from the coronavirus disease 2019 (COVID-19) pandemic on the 
study benefit–risk assessment or the existing study safety monitoring and risk mitigation 
measures. Patients with symptomatic disease (including COVID-19) at screening will be 
excluded and enrolled participants will be closely monitored for new/emerging infections. 
More detailed information about the known and expected benefits in the context of 
potential risks and reasonably expected AEs of RO7565020 is provided in the IB. 

 
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3. 
OBJECTIVES AND ENDPOINTS 
The objectives and corresponding endpoints are provided in Table 5. 
Table 5 
Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
 
To assess the safety and tolerability:  
o 
following a single dose of 
RO7565020 administered 
subcutaneously (SC) or intravenously 
(IV) to healthy participants (Part 1a) 
and SC to virologically suppressed 
participants with chronic hepatitis B 
(CHB) (Part 2) 
o 
following multiple doses of 
RO7565020 administered SC to 
healthy participants (Part 1b) and 
virologically suppressed participants 
with CHB (Part 3) 
 
Frequency and severity of adverse events 
(AEs), including adverse events of special 
interest (AESI), serious adverse events 
(SAE), and treatment discontinuations due 
to AEs 
 
Frequency of abnormal laboratory findings 
based on hematology, blood chemistry 
(including liver function tests), coagulation 
and urinalysis test results 
 
Frequency of clinically significant 
abnormalities in ECGs and vital signs 
 
Mean changes from baseline in vital signs 
(temperature, systolic and diastolic blood 
pressure, pulse rate, respiratory rate) over 
time 
Secondary 
 
To investigate the serum 
pharmacokinetics of RO7565020: 
o 
following single-ascending doses of 
RO7565020 administered SC or IV to 
healthy participants (Part 1a) and SC 
to virologically suppressed 
participants with CHB (Part 2) 
o 
following multiple doses of 
RO7565020 administered SC to 
healthy participants (Part 1b) and 
virologically suppressed participants 
with CHB (Part 3) 
 
PK parameters of RO7565020:  
o 
Time to maximum concentration (tmax) 
o 
Maximum serum concentration 
observed (Cmax) 
o 
AUC from Time 0 to time of last 
sampling point or last quantifiable 
sample, whichever comes first  
(AUC0-last) 
o 
AUC from Time 0 to infinity (AUCinf) 
o 
Terminal half-life (t1/2) 
o 
Volume of distribution (Vss) and 
clearance (CL) (IV only) 
o 
Apparent clearance (CL/F), apparent 
volume of distribution at terminal 
phase (Vz/F) (SC only) 

 
RO7565020—F. Hoffmann-La Roche Ltd 
34/Protocol BP44118, Version 3 
Table 5 
Objectives and Endpoints (cont.) 
Objectives 
Endpoints 
Secondary (cont.) 
 
To characterize the antiviral response 
after a single dose or multiple doses of 
RO7565020 in virologically suppressed 
participants with CHB (Parts 2 and 3, 
respectively) 
 
Change from baseline in serum 
quantitative hepatitis B surface antigen 
(HBsAg) 
 
Maximum reduction from baseline of 
serum HBsAg across all timepoints 
 
Proportion of participants with HBsAg loss 
(on quantitative and qualitative HBsAg 
assays) 
 
Proportion of participants with HBsAg 
seroconversion (sustained loss of HBsAg 
and detection of anti-HBs antibody) 
 
Proportion of participants with hepatitis B 
e antigen (HBeAg) loss among HBeAg-
positive participants at baseline 
 
Proportion of participants with HBeAg 
seroconversion (sustained loss of HBeAg 
and detection of anti-HBe antibody) 
among HBeAg-positive participants at 
baseline 
 
To assess the immunogenicity (induction 
of anti-drug antibodies [ADAs]) of 
RO7565020 in healthy participants and 
virologically suppressed participants with 
CHB 
 
ADA prevalence at baseline 
 
Incidence and titer of ADA over time 
Exploratory 
 
To characterize the relationship between 
HBsAg at baseline, the serum 
concentration of RO7565020 and the 
maximum reduction of HBsAg (Parts 2 
and 3) 
 
Model parameters describing 
relationships between ratio of 
RO7565020/HBsAg at baseline and 
maximum HBsAg reduction 
 
To explore the potential impact of ADA 
on safety and PK/PD after single dose or 
multiple doses of RO7565020 in healthy 
participants (Part 1) and virologically 
suppressed participants with CHB 
(Parts 2 and 3) 
 
Relationship between ADA, safety, and 
PK/PD 
 
To explore the effect of RO7565020 on 
other viral biomarkers, such as HBeAg 
(calculated), HBV RNA, hepatitis B core-
related antigen (HBcrAg), total HBsAg 
after HBsAg:HBsAb complex 
dissociation, and HBsAg isoforms 
(Parts 2 and 3) 
 
Baseline and change from baseline in 
HBeAg (calculated), HBV RNA levels, 
HBcrAg levels, total HBsAg (after 
HBsAg:HBsAb complex dissociation), 
and distribution of HBsAg isoforms 
 
To explore the relationship between 
baseline disease characteristics and 
efficacy/safety responses (Parts 2 
and 3) 
 
Association of the primary and secondary 
endpoints with the HBV genotype, 
baseline HBeAg status, and baseline 
exploratory parameters (such as HBV 
RNA, HBcrAg, total anti-HBc, HBsAg 
isoforms)  

 
RO7565020—F. Hoffmann-La Roche Ltd 
35/Protocol BP44118, Version 3 
Table 5 
Objectives and Endpoints (cont.) 
Objectives 
Endpoints 
Exploratory (cont.) 
 
To explore the relationship between 
HBsAg decrease, HBsAg-HBsAb 
immune complex formation, and the 
recovery of the immune response 
(Parts 2 and 3) 
 
Baseline and change from baseline of 
cytokines and other soluble markers of 
immune activation and inflammation 
 
Changes in immune cell subsets and 
activation status (flow cytometry/ICS) 
and antigen-specific immune response 
(ELISpot/FluoroSpot) at baseline and 
post-treatment (PBMC samples) 
 
Baseline and changes from baseline in 
the transcriptional profile of immune cells 
subsets in peripheral blood (host gene 
sc-RNAseq) 
 
To explore the relationship between 
potential AEs and inflammatory cytokines 
released in healthy participants (Part 1) 
and participants with CHB (Parts 2 
and 3)  
 
Association between cytokines and other 
soluble markers of immune activation 
and inflammation with AEs 
 
To monitor the potential emergence of 
RO7565020-resistant variants and their 
impact on efficacy/safety outcomes 
(Parts 2 and 3) 
 
Baseline and changes in free and total 
HBsAg over time in relationship to 
RO7565020 PK 
 
Baseline and changes from baseline in 
binding affinity of RO7565020 to HBsAg 
 
Baseline and changes from baseline in 
the clonality of the S gene sequences 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
36/Protocol BP44118, Version 3 
4. 
STUDY DESIGN 
4.1 
OVERALL DESIGN 
An overview of the study design is provided in Section 1.2. 
This is a FIH, multi-center, dose-finding, and dose-escalation Phase I clinical study of 
RO7565020 to investigate the safety and tolerability and to characterize the 
pharmacokinetics, ADA, pharmacodynamics, and preliminary antiviral responses 
following single and/or multiple doses of RO7565020 in healthy participants and/or 
virologically suppressed participants with CHB. RO7565020 will be administered via SC 
injection in healthy participants and participants with CHB, and by IV infusion to healthy 
participants only. The study will be conducted in three parts: Part 1a is a SAD study in 
healthy participants with at least 8 participants per cohort. Part 1b is an optional, 
multiple-dose study with 8 healthy participants in 1 cohort. Part 2 is a SAD study in 
virologically suppressed participants with CHB with 6 participants in each cohort. 
Participants will be enrolled into Parts 2a and 2b on the basis of the baseline HBsAg 
level (cutoff: 3000 IU/mL). Part 3 is an optional, multiple-dose study with 6 virologically 
suppressed participants with CHB per cohort (see Figure 1). 
A Dose Decision Team (DDT) will review emerging study data and make 
recommendations regarding dose escalation and overall study conduct (see 
Section 4.1.1.2). The dose escalation will be stopped according to stopping rules criteria 
(see Section 4.1.1.3). Additional dose cohorts that assess lower or repeat doses may be 
investigated; however, dose modifications of the RO7565020 doses of individual 
participants are not permitted during the study. 
Part 1a – SAD in Healthy Participants 
Part 1a is a 6:2 randomized, Sponsor-open (i.e., Investigator-blinded, participant-
blinded), placebo-controlled SAD study in healthy participants to assess the safety, 
tolerability, pharmacokinetics, and immunogenicity (in the absence of HBsAg) following 
SC injection or IV infusion of RO7565020 or placebo. An ethnic-specific cohort is also 
included for the purpose of PK bridging between a global population and Chinese 
population.  
Four provisional escalating dose levels are planned to be administered sequentially to 
6 different cohorts of participants (see Table 6), The anticipated ascending-dose scheme 
is 70 mg SC, 230 mg SC, 360 mg SC, 360 mg IV, and 9001500 mg IV or matching 
placebo. Cohort 6 (ethnicity bridging cohort: 360 mg SC or matching placebo) may be 
conducted in parallel with Cohort 4 after the preliminary safety evaluation in Cohort 3 is 
completed and considered safe. 
Each participant within a given cohort will randomly receive single doses of RO7565020 
or matching placebo at the assigned dose via SC injection or IV infusion (see Table 6). 

 
RO7565020—F. Hoffmann-La Roche Ltd 
37/Protocol BP44118, Version 3 
Each cohort will enroll 8 participants to allow for a dose escalating decision. Sentinel 
dosing will be applied to each cohort, i.e., initially, 2 participants in each cohort will be 
randomized and dosed (1 with RO7565020 and 1 with placebo). Safety will be evaluated 
for at least 72 hours after the second sentinel participant has been dosed and if the 
safety data for the sentinel participants obtained in the 72-hour postdose period are 
judged acceptable by the Investigator, the remaining participants of the cohort will be 
dosed. 
The study design is adaptive in nature and other intermediate doses may be investigated 
based on emerging safety and tolerability data. The IV formulation will be used to 
evaluate the absolute bioavailability of SC formulation, and to provide a higher PK 
exposure that covers the highest PK exposure (maximum concentration [Cmax] and area 
under the time-concentration curve within a dosing interval [AUCtau]) anticipated after 
multiple doses of SC administration in future Phase II studies. 
Part 1b – Multiple Doses in Healthy Participants 
Part 1b is an optional, 6:2 randomized, Sponsor-open, placebo-controlled multiple-dose 
study in healthy participants. If, for example, an unexpected impact on the PK profile due 
to ADA formation is observed in Part 1a, Part 1b might be initiated to further investigate 
the safety and pharmacokinetics of RO7565020 following multiple doses. 
One dose cohort is planned for Part 1b, and each participant will randomly receive 
multiple doses of RO7565020 or matching placebo via SC injection. The dose and 
dosing frequency will be determined by emerging safety and PK data from Part 1a.  
In this Part 1b cohort, sentinel dosing will be applied for each dosing to allow an 
evaluation of safety data for at least 72 hours after the first 2 participants have been 
dosed (1 with RO7565020 and 1 with placebo). If the safety data for the sentinel 
participants obtained in the 72-hour postdose period are judged acceptable by the 
Investigator, the remaining participants will be dosed. 
Part 2 – SAD in Participants with CHB 
Part 2 is an open-label, SAD study of RO7565020 administered by SC injection in 
participants with CHB who are virologically (HBV DNA) suppressed with stable NUC 
treatment, including tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), or 
entecavir (ETV). Part 2 aims to assess the safety and tolerability including the potential 
for HBsAg:HBsAb complex-mediated immune reactions, pharmacokinetics, and 
pharmacodynamics of RO7565020 in participants with CHB. In addition, proof of 
mechanism will also be explored by measuring the changes in HBsAg level after 
treatment. Participants with 20 IU/mL  HBsAg  3000 IU/mL will be enrolled into 
Part 2a. Participants with HBsAg  3000 IU/mL will be enrolled into Part 2b (upper limit of 
10,000 IU/mL in Cohorts 1 and 2). 

 
RO7565020—F. Hoffmann-La Roche Ltd 
38/Protocol BP44118, Version 3 
Three and four cohorts are planned for Part 2a and Part 2b, respectively. The provisional 
escalating dose levels are shown in Table 6. Before proceeding to higher dose levels, 
the safety and tolerability at lower dose levels will be reviewed by the DDT and 
considered to be safe. 
Part 2a Cohort 1 will be initiated after at least 6 participants (5 on active treatment and 
1 on placebo) in Part 1a Cohort 2 (i.e., a higher dose level in healthy participants) have 
completed the 28-day follow-up and the dose level is considered to be safe. The 
initiation of Part 2b (in participants with HBsAg  3000 IU/mL) will be staggered until at 
least 5 participants (all on active treatment) at the same dose level in Part 2a 
(HBsAg  3000 IU/mL) have completed at least 28 days of follow-up and the dose level 
is considered to be safe (see Section 4.1.1). Part 2b Cohort 1 (optional) is designed to 
assess the target-mediated drug disposition (TMDD) effect on the clearance of anti-HBs 
mAbs, and the need for this Cohort will be determined after the data from Cohort 1 (Part 
2a) are available. If Part 2b Cohort 1 is not needed, Part 2b Cohort 2 will start after at 
least 5 participants in Part 2a Cohort 2 have completed at least 28 days of follow-up and 
the dose is considered to be safe. The conduct of Cohort 4 in Part 2b (optional) will be 
determined by whether a higher dose (720 mg or higher) is required in a high HBsAg 
population to achieve a meaningful HBsAg reduction and maintenance based on the 
neutralization potency of RO7565020 in the first 3 cohorts in Part 2b. 
Each cohort will enroll 6 participants to allow for a dose-escalation decision. Sentinel 
dosing of the first participant will be applied to each cohort to allow an evaluation of 
safety data for at least 72 hours postdose. If the safety data of the sentinel participant 
obtained in the 72-hour postdose period are judged acceptable by the Investigator, the 
remaining participants can be dosed. 
The HBsAg level of the first 2 participants recruited in Part 2b Cohort 3 and Part 2b 
Cohort 4 is required to be 10,000 IU/mL. A participant with HBsAg  10,000 IU/mL at 
screening will be on hold until at least 2 participants with HBsAg  3000 IU/mL but 
 10,000 IU/mL have been dosed and the dose is considered to be safe after 28 days of 
follow-up. 
Part 3 (Optional) – Multiple Doses in Participants with CHB 
On the basis of emerging data including safety, tolerability, PK and pharmacodynamic 
(PD) data from Parts 1 and 2, Part 3 may be initiated as an open-label cohort in 
participants with virologically suppressed CHB to assess safety, tolerability, 
pharmacokinetics, pharmacodynamics, and antiviral response after multiple doses of 
RO7565020 via SC injection, if, e.g., an unexpected PK/PD profile is observed due to 
ADA formation, or if the dose and dosing interval for the multiple-dose Phase II regimen 
could not be reliably determined from the single dose PK/PD data. 

 
RO7565020—F. Hoffmann-La Roche Ltd 
39/Protocol BP44118, Version 3 
In Part 3, 6 eligible virologically suppressed participants with CHB are planned to be 
enrolled in each cohort, for a maximum of 2 cohorts. The dose level and frequency will 
be determined by the emerging data in Parts 1 and 2. Sentinel dosing will also be 
applied for each dosing in Part 3 to allow an evaluation of safety data for at least 
72 hours after the first participant has been dosed. If the safety data for the sentinel 
participant obtained in the 72-hour postdose period are judged acceptable by the 
Investigator, the remaining participants can be dosed. 
In Parts 2 and 3, all participants will continue to receive NUC therapy throughout the 
study, even if HBsAg loss is achieved. Participants should avoid changing NUC during 
the study including screening period, unless the Investigator considers it necessary for 
medical reason (e.g., virological breakthrough [Section 8.3.7], safety). 
Table 6 
Provisional Dose Regimens in Each Study Cohort 
Study part 
Study treatment 
Background 
treatment 
Part 1a (healthy 
participants) 
 
Cohort 1: 70 mg RO7565020 SC (starting 
dose) or placebo, single dose 
 
Cohort 2: 230 mg RO7565020 SC or placebo, 
single dose 
 
Cohort 3: 360 mg RO7565020 SC or placebo, 
single dose 
 
Cohort 4: 360 mg RO7565020 IV or placebo, 
single dose (over 2-hour infusion) 
 
Cohort 5: 900–1500 mg RO7565020 IV or 
placebo, single dose (over 2-hour infusion) 
 
Cohort 6 (PK bridging cohort): 360 mg 
RO7565020 SC or placebo, single dose 
N/A 
Part 1b (healthy 
participants) 
 
Multiple doses (3 to 6 doses depending on 
dosing frequency). Dose level and dosing 
frequency will be determined using Part 1a 
data 
N/A 
Part 2a (participants 
with CHB) 
 
Cohort 1: 70 mg RO7565020 SC (starting 
dose), single dose  
 
Cohort 2: 230 mg RO7565020 SC, single dose  
 
Cohort 3: 360 mg RO7565020 SC, single dose 
NUC 
Part 2b (participants 
with CHB) 
 
Cohort 1 (optional): 70 mg RO7565020 SC, 
single dose  
 
Cohort 2: 230 mg RO7565020 SC, single dose  
 
Cohort 3: 360 mg RO7565020 SC, single dose 
 
Cohort 4 (optional): 720 mg RO7565020 SC, 
single dose 
NUC 

 
RO7565020—F. Hoffmann-La Roche Ltd 
40/Protocol BP44118, Version 3 
Table 6 
Provisional Dose Regimens in Each Study Cohort (cont.) 
Study part 
Study treatment 
Background 
treatment 
Part 3 (participants 
with CHB) 
 
Multiple doses (up to 6 doses depending on 
dosing frequency). Dose level and dosing 
frequency will be determined using Part 1 and 
Part 2 data 
NUC 
Abbreviations: CHB = chronic hepatitis B; IV = intravenous; N/A = not applicable; 
NUC = nucleos(t)ide analogue; PD = pharmacodynamic; PK = pharmacokinetic; 
SC = subcutaneous. 
Note: Depending on the evaluation of the safety and/or PK/PD data, the same dose may be 
repeated; the actual dose may be modified to a lower dose; or intermediate dose-escalation 
steps other than those anticipated above may be used at the discretion of the Investigator 
and the Sponsor. 
 
4.1.1 
Dose Escalation 
 
4.1.1.1 
Dose-Escalation Decision Criteria 
The decision to escalate to the next dose level and cohort will be made by the DDT 
following a review of all available safety and tolerability data, including AEs, ECGs, vital 
signs, and laboratory safety test results (i.e., hematology, clinical chemistry and 
urinalysis, etc.) collected at least 28 days postdose from a minimum of 6 participants 
(5 on active treatment and 1 on placebo) in Part 1, or a minimum of 5 participants on 
active treatment in Part 2, as well as available serum PK, PD, and ADA data up to 
28 days postdose from a minimum of 5 participants on active treatment. 
In addition, all available safety, tolerability, PK, PD, and ADA data from all previous dose 
level(s) will be reviewed. Dose escalation will only occur if the previous doses were 
tolerated and stopping rules were not met. 
Dose-escalation steps will not exceed 5-fold increments.   
4.1.1.2 
Dose Decision Team 
A DDT will review emerging study data and make recommendations regarding dose 
escalation and overall study conduct to ensure participant safety while receiving study 
treatment. The DDT will consist of the Investigators and the Sponsor members, 
collectively having expertise in clinical science, clinical pharmacology, 
pharmacodynamics, statistics, and clinical safety and will include at least one physician. 
Additional advisors may be consulted as deemed appropriate. The DDT will review 
emerging data that become available and will be empowered to pause, stop, or continue 
the study, or to continue it with modifications. Additional information about the DDT can 
be found in a separate Dose Escalation Plan (DEP). 

 
RO7565020—F. Hoffmann-La Roche Ltd 
41/Protocol BP44118, Version 3 
4.1.1.3 
Stopping Rules Criteria 
4.1.1.3.1 
Cohort Stopping Rules 
 
Part 1 
Dose escalation will be stopped and dosing at a given level will be stopped if one of the 
following circumstances occurs in participants treated with RO7565020 within the same 
dose cohort: 
 
Severe non-serious adverse reactions (Grade 3 or above, as per Division of AIDS 
[DAIDS] grading, v2.1, considered to be related to RO7565020) in 2 or more 
participants receiving RO7565020 in the same cohort, independent of the system 
organ classes. 
 
Any serious adverse reaction in 1 participant (i.e., a serious AE [SAE] considered to 
be related to RO7565020). 
 
Grade 2 or above clinically significant laboratory abnormalities, vital sign change, or 
ECG change, of the same type in 3 or more participants receiving RO7565020 in 
the same cohort. 
 
Other findings, which at the discretion of the DDT, indicate that dose escalation or 
dosing at that dose level should be stopped. 
 
Dose escalation will also be stopped if increasing the dose does not result in a 
significant increase in serum exposure of RO7565020. 
 
Parts 2 and 3 
Dose escalation and dosing at a given level of RO7565020 will be temporarily halted if 
one of the following circumstances occurs. Dosing might be resumed if deemed 
appropriate following the DDT review of the available safety, PK, and PD data. Relevant 
reporting and discussion with relevant DDT personnel and the Institutional Review Board 
(IRB)/ Independent Ethics Committee (IEC) will take place before potential resumption of 
dosing. 
 
Severe non-serious adverse reactions (Grade 3 or above, as per DAIDS grading, 
v2.1, considered to be related to RO7565020) in 2 or more participants receiving 
RO7565020 in the same cohort, independent of the system organ classes 
 
Any serious adverse reaction in 1 participant (an SAE considered to be related to 
RO7565020) 
 
Other findings which, at the discretion of the DDT members, indicate that dose 
escalation or dosing at that level should be stopped 
 
In case dose escalation is stopped, lower doses within the tolerated dose range could be 
investigated or a dose repeated in subsequent cohorts to increase the amount of data 
within this tolerated dose range. 

 
RO7565020—F. Hoffmann-La Roche Ltd 
42/Protocol BP44118, Version 3 
4.1.1.3.2 
Individual Participant Stopping Rules 
Infusion of RO7565020 will be stopped immediately (for an individual participant in the IV 
cohorts), and the participant will be discontinued from further treatment with RO7565020 
(for an individual participant in the multiple-dosing cohorts), if the participant experiences 
any of the following: 
 
Severe non-serious adverse reactions (Grade 3 as per DAIDS grading, v2.1, 
considered to be related to RO7565020) 
 
Serious adverse drug reaction (i.e., an SAE considered to be related to 
RO7565020) 
 
Other findings which, at the discretion of the DDT members, indicate that dosing 
should be stopped 
 
4.1.1.4 
Communication Strategy 
Information will be communicated, as follows: 
 
For all participants, during dose escalation in the study, the Investigator(s) must 
confirm to the Sponsor that the participant has been dosed and provide a brief 
summary of the status of the participant in terms of safety and tolerability to 
RO7565020, communicated by email and/or telephone. 
 
In the event of a severe AE or an SAE, the Investigator will contact the Sponsor 
immediately to discuss participant status and action taken/to be taken. 
 
After at least 28 days postdose from a minimum of 6 participants (5 on active 
treatment and 1 on placebo) in Part 1, or a minimum of 5 participants on active 
treatment in Part 2: The Sponsor will organize a teleconference with the 
Investigators to discuss the safety and tolerability of RO7565020 and to discuss the 
dose(s) for the next cohort. If the teleconference occurs prior to the end of the dose 
evaluation period, the Investigator will provide a final status prior to the start of the 
next cohort.  
During each teleconference: 
– 
AEs (see Appendix 2) will be discussed along with the results of PK data 
(if available), in addition to safety laboratory results and any other available 
data that may assist the dose escalation decision process.  
– 
Dose escalation will only proceed to the next dose level if DDT are satisfied 
with the safety profile of the previous cohort and agree to move to the next 
dose level.  
– 
If other RO7565020 dose levels are explored, it will be documented in 
writing, and both the Sponsor and Investigators will approve the minutes of 
these meetings to confirm agreement. 
 
In addition to these communications, the Sponsor and Investigators will be in regular 
contact throughout the study, as per normal interactions during the conduct of a clinical 
study, and the Sponsor will arrange regular teleconferences and meetings to discuss 
study status. 

 
RO7565020—F. Hoffmann-La Roche Ltd 
43/Protocol BP44118, Version 3 
4.2 
SCIENTIFIC RATIONALE FOR STUDY DESIGN 
The study rationale is provided in Section 2.1. 
4.2.1 
Rationale for Study Population 
Part 1 will be conducted in healthy male participants, and female participants of non-
childbearing potential or who agree to take contraceptive measures as required by the 
study, 18 to 65 years of age. The absence of potentially confounding diseases and 
co-medications (except for hormonal contraceptives for female participants) in healthy 
volunteers allows for a clearer and more consistent assessment of drug disposition, 
safety, tolerability, and ADA formation. 
Parts 2 and 3 will be conducted in virologically suppressed participants with CHB, 
between 18 and 65 years of age, with preserved liver function and without significant 
fibrosis/cirrhosis. This population is considered optimal to evaluate the proof of 
mechanism of RO7565020 in humans as the first patient population. The virologically 
suppressed participants have a more stable disease phenotype compared to treatment-
naive patients who have elevated and fluctuating ALT levels, and the lower baseline 
HBsAg levels may increase the likelihood of attaining a treatment response. The study 
population is associated with a favorable benefit/risk profile and is considered 
appropriate for early phase clinical trials of novel CHB therapies within the current 
guidelines (FDA 2022). 
As the participants enrolled in Parts 2a and 2b have different HBsAg levels at baseline, 
the proposed study will provide essential support for the selection of the RO7565020 
multi-dose regimen for the future Phase II study in patients with CHB. Additionally, the 
safety, tolerability, and pharmacokinetics data, including the TMDD effect after single or 
multiple SC doses of RO7565020, will also provide essential information for supporting 
the future development of this target population. 
4.2.2 
Rationale for Control Group 
In each cohort in Part 1a and in Part 1b, participants will be randomized (Sponsor-open, 
Investigator-blinded, and participant-blinded) at 6:2 to receive RO7565020 and placebo, 
respectively. This is considered sufficient to allow for unbiased comparisons of safety 
and tolerability of active treatment to placebo both within and across cohorts in absence 
of HBsAg. 
It is considered unnecessary to include placebo controls in Parts 2 and 3, because 
placebo controls have negligible impact on HBsAg change over time, and the off-target 
safety profile at the same dose will have been assessed in healthy participants and the 
AEs in the presence of HBsAg would be most likely be of an immunological nature (e.g., 
as a consequence of HBsAg:HBsAb complex formation and possible tissue deposition) 
that can be easily attributed. 

 
RO7565020—F. Hoffmann-La Roche Ltd 
44/Protocol BP44118, Version 3 
4.2.3 
Rationale for Biomarker Assessments 
4.2.3.1 
HBV Dynamic Biomarkers 
RO7565020 is a human IgG1 neutralizing antibody, which showed potent and cross-
reactive in vitro neutralization against all main circulating viral genotypes of HBsAg. 
Therefore, the main virological endpoint in this study relies on measuring HBsAg at 
timepoints defined in the SoA (Section 1.3). 
Additional well-established HBV dynamic biomarkers for the assessment of HBV 
treatment outcomes will include the time course of anti-HBs levels and the evolution of 
the HBeAg and anti-HBe statuses. In participants who are HBeAg-positive at study 
entry, a validated research-use-only (RUO) semi-quantitative calculation may be used to 
follow the time course of serum HBeAg levels over time. In order to evaluate the 
formation of HBsAg:HBsAb complexes, an assay is being developed by the Sponsor that 
may be used to either directly quantify the immune complexes or measure HBsAg 
independently of the putative formation of complexes (i.e., total HBsAg post-dissociation 
of HBsAg:HBsAb complexes), as appropriate. Additionally, quantification of HBsAg may 
be measured using a second assay designed to either evaluate a potential bias of the 
HBsAg quantitative assay being used or to measure a change in the affinity of 
RO7565020 to escape mutants that might be selected for by therapy with RO7565020. 
Several HBV biomarkers have recently emerged in the field that may further support the 
demonstration of improved virus control. These novel biomarkers will not be used to 
screen participants and will not have an impact on any clinical decisions or other 
endpoint evaluation. 
Among these, pregenomic HBV RNA, which bypasses reverse transcription and is 
released in plasma, may provide a direct measure of the transcriptional activity of 
cccDNA. Consistent with this view, in NUC-treated participants with suppressed HBV 
DNA, the presence of detectable circulating HBV RNA signals an increased probability 
of HBV DNA rebound upon NUC cessation (Wang et al. 2016; Fan et al. 2020; 
Seto et al. 2021; Kaewdech et al. 2020). In the course of this study, a validated real-time 
polymerase chain reaction-based investigational assay may be used to quantify HBV 
RNA. 
Circulating hepatitis B core-related antigen (HBcrAg) levels provide one additional 
biomarker that could support demonstration of the achievement of virus control. HBcrAg 
is a composite circulating biomarker comprising hepatitis B core antigen (HBcAg, which 
is part of HBV virions), HBeAg (which arises from the same open reading frame as 
HBcAg and is secreted), and p22cr (precore protein). Emerging data correlate HBcrAg 
measurements with cccDNA levels and activity and HBV treatment outcomes 
(Mak et al. 2018; Chen et al. 2017; Inoue and Tanaka 2020; Li et al. 2020). In the course 
of this study, a validated RUO method based on a quantitative enzyme-linked 
immunosorbent assay may be used to quantify HBcrAg in serum. 

 
RO7565020—F. Hoffmann-La Roche Ltd 
45/Protocol BP44118, Version 3 
Antibodies against HBcAg (anti-HBc) are the first to appear during the acute phase of 
infection. The IgM anti-HBc levels gradually disappear and are followed by the 
production of IgG anti-HBc. Novel assays for the quantification of IgG or total anti-HBc 
have been developed. The levels of this biomarker have been shown to vary through the 
different phases of the CHB infection. They are higher during the immune clearance and 
reactivation phases than during the immune tolerance and inactive carrier phases. 
Moreover, high levels of IgG or total anti-HBc correlate with a higher rate of HBeAg 
seroconversion in HBeAg-positive patients treated with NUCs. In the course of this 
study, a validated RUO method may be used to quantify total anti-HBc in serum 
(Jia et al. 2014; Yuan et al. 2013; Fan et al. 2016). 
The HBsAg messenger RNA contains three in-frame start codons that lead to the 
production of three HBsAg isoforms: S-HBsAg, M-HBsAg, and L-HBsAg, where S, M, 
and L indicate selective, medium, and large, respectively. The S-HBsAg contains four 
membrane-spanning domains as well as the “a”-determinant (i.e., the primary antigenic 
site of HBsAg). In addition to these domains, M-HBsAg contains an additional amino 
terminal preS2 sequence, and L-HBsAg contains both amino terminal preS1 and preS2 
sequences (Bruss 2007; Brown et al. 1984; Patient et al. 2009; Laub et al. 1983). With 
spherical subviral particles (SVPs) forming the majority of circulating HBsAg and 
consisting of 95% of S-HBsAg, this isoform is the major circulating HBsAg isoform. 
However, while M-HBsAg and L-HBsAg are found during acute and chronic infection, 
their levels have been proposed to drop significantly in inactive HBV carriers, consistent 
with the reduced viremia observed in this patient population. Additionally, a recent study 
has observed that selective declines in M-HBsAg and L-HBsAg precede HBsAg loss 
during NUC therapy in HBeAg-positive HBV infection. (Pfefferkorn et al. 2018, 2021). 
Therefore, in the course of this study, an RUO method may be used to quantify the 
different HBsAg isoforms using a validated assay currently being developed by the 
Sponsor. 
4.2.3.2 
HBV Genotype 
The initial participant population recruited in this study will be established on effective 
NUC therapy at study entry and will have circulating HBV DNA levels below the assay 
lower limit of quantification (defined as below 10 IU/mL) for at least 6 months, confirmed 
at screening. Response to therapy could potentially be modulated by the HBV genotype. 
To determine HBV genotype in participants with undetectable HBV DNA, Sanger or 
deep sequencing may be attempted in some participants using amplified HBV RNA from 
a plasma sample collected on Day 1 or at any follow-up timepoint, as appropriate. 
Alternatively, the HBsAg serotype may be determined as a surrogate for HBV genotype 
using the same sample.  
4.2.3.3 
HBV DNA Monitoring and Viral Resistance 
During the study, participants will be monitored to ensure that HBV DNA suppression by 
the NUC therapy is maintained. Participants who experience HBV DNA breakthrough 
(HBV DNA > 100 IU/mL) while on NUC therapy will be recalled for repeat testing. If the 

 
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HBV DNA level is confirmed to be more than 100 IU/mL, the participants will be 
assessed for evidence of drug resistance using sequencing and potentially phenotyping. 
The sample will also be used to determine the HBV genotype. NUC and RO7565020 PK 
samples will also be collected. 
Moreover, to evaluate the potential resistance to RO7565020 in absence of a 
concomitant DNA breakthrough, changes in the levels of free and total HBsAg and 
changes in the affinity of RO7565020 to potential escape mutants in the S gene that 
might have been selected for may be measured using baseline, end of follow-up, and/or 
intermediary timepoint samples. The characterization of such emerging mutations may 
be attempted through HBV RNA sequencing, if feasible. 
4.2.3.4 
Immunological Biomarkers 
RO7565020 is a human neutralizing antibody (Ab) that shows potent reduction in 
circulating HBsAg in nonclinical models. The fully human origin of RO7565020 is 
expected to reduce immune-related risks (e.g., ADA or immune complex formation; 
Heyen et al. 2014; Vaisman-Mentesh et al. 2020). Nevertheless, soluble markers of 
immune activation and inflammation (soluble cytokines and chemokines which may 
include IFN- tumor necrosis factor- [TNF-, interleukin [IL]-6 and IL-8) as well as 
complement components (e.g., C3a and SC-5b9) may be assessed. Measures of 
systemic immune activation and inflammation will be correlated with the safety profile of 
RO7565020 in participants. Additionally, specific cytokines and chemokines may be 
tested to explore correlations with immunological or virological data of interest in CHB 
cohorts. 
Growing literature evidence shows that long-term exposure to high concentrations of 
viral antigens, in particular HBsAg, results in host immune response suppression, 
including T cell exhaustion, B cell impairment, and immune tolerance induced by other 
myeloid cells (e.g., natural killer [NK] cells; Iannacone and Guidotti 2022). It is 
hypothesized that reducing the levels of circulating HBsAg will in turn restore the 
immune response towards HBV. How this reduction in HBsAg may translate into the 
restoration of measurable HBV-specific immune responses in peripheral blood during or 
after the end of dosing is currently unclear. The transcriptional profile and inflammatory 
signature (single-cell RNA sequencing [scRNAseq]) may be assessed from blood in 
participants with CHB. Circulating immune phenotype, B and T cell activation status 
(flow cytometry) and HBV-specific cellular immune phenotype and function 
(e.g., Flurospot, tetramer staining, fluorescent bait) may be tested ex vivo in CHB 
participants using cryopreserved peripheral blood mononuclear cells (PBMCs) collected 
at timepoints indicated in the SoA (see Section 1.3). These analyses will be considered 
as an exploratory optional objective, taking into consideration the logistic and technical 
challenges that might be experienced with the collection of viable PBMCs during the 
conduct of a multi-center trial. 

 
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Whole blood samples for human DNA extraction will be taken from participants with 
CHB. The intended use of these is to determine human leukocyte antigen (HLA) types, 
necessary for the subsequent isolation and characterization of HBV-specific immune 
cells from PBMCs, using HLA-matching reagents (e.g., multimers). Any data arising from 
clinical genotyping will be subject to the confidentiality standards described in 
Appendix 1, Section 4. 
4.2.4 
Justification for Dose 
The starting dose of 70 mg (SAD portions of Part 1 and Part 2) has been selected to 
balance considerations for an acceptable safety margin and the predicted efficacious 
dose in humans. RO7565020 was well tolerated at a dose level of 360 mg/kg when 
administered to cynomolgus monkeys via SC injection or IV once weekly for 3 weeks, 
thus 360 mg/kg was considered to be a no-observed-adverse-effect level (NOAEL) for 
both dose routes. 
The observed PK exposure (e.g., area under the time-concentration curve from 0 to 
21 days [AUC0-21d] and Cmax) at NOAEL is  100 times higher than the predicted AUCinf 
and Cmax values in humans at the proposed starting dose of 70 mg SC, and ~11 and 22 
times higher than the predicted AUCinf and Cmax values, at the planned highest dose of 
1.5 g IV in SAD (Part 1a), respectively. 
Starting from a single dose of 70 mg in healthy participants also establishes a link to the 
starting dose in participants with CHB. Based on a PK/PD model, the starting dose of 
70 mg in Part 2a is expected to produce a meaningful maximum decline 
( 1 log10 IU/mL) in free HBsAg concentrations in all participants with baseline HBsAg 
levels  3000 IU/mL after a single SC dose of RO7565020. 
The planned higher doses (230 mg SC and 360 mg SC) in Part 2a and Part 2b are 
aiming to achieve greater and more sustained HBsAg reductions in participants with 
different baseline HBsAg level. 
Switching to IV formulation in Part 1a is designed to test a higher dose in healthy 
participants, which exceeds the maximum SC dose (360 mg) that is feasible with one 
injection; Part 1a Cohort 5 (9001500 mg) aims to cover the maximum PK exposure due 
to PK accumulation after multiple doses.  In the meantime, absolute bioavailability of the 
SC formulation will be evaluated based on the PK data in Cohort 3 and Cohort 4, 
Part 1a. 
Further details are provided in the RO7565020 IB. 
4.3 
DURATION OF PARTICIPATION 
The duration of each study period is described in Table 7. 

 
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Table 7 
Duration of Study Periods 
Study 
Part 
Screening 
Treatment 
period 
In-clinic period 
End-of-study visit*** 
Part 1a 
Up to 28 days 
Day 1 
Day 1 to Day 4 
36 weeks after study treatment 
administration 
Part 1b 
Up to 28 days 
Up to 
169 days 
Day 1 to Day 4, 
and 1 day after each 
administration for 
the following doses, 
including optional 
overnight stay* 
36 weeks after the final study 
treatment administration 
Parts 2a 
and 2b 
Up to 56 days 
(Pregnancy 
testing and 
liver function 
up to 14 days) 
Day 1 
Day 1** to Day 4, 
including optional 
overnight stay* 
24 weeks after study treatment 
administration 
(If HBsAg does not return to 
baseline level at follow-up 
Week 24, will have additional 
follow-up visits until returns 
to  0.1 log below baseline for two 
consecutive visits, or up to 
56 weeks postdose, whichever 
comes first.) 
Part 3 
Up to 56 days 
(Pregnancy 
testing and 
liver function 
up to 14 days) 
Up to 
337 days 
Day 1** to Day 4, 
and 1 day after each 
administration for 
the following doses, 
including optional 
overnight stay* 
24 weeks after last study 
treatment administration  
(If HBsAg does not return to 
baseline level at follow-up 
Week 24, will have additional 
follow-up visits until return 
to  0.1 log below baseline for two 
consecutive visits, or up to 
56 weeks post the final dose, 
whichever comes first.) 
Abbreviations: ADA = anti-drug antibody; HBsAg = hepatitis B surface antigen; 
PK = pharmacokinetic. 
Note: Participants who permanently discontinue from the study (or study treatment) due to 
Sponsor’s decision (e.g., Sponsor prematurely terminates the study) will undergo safety 
follow-up for 24 weeks or longer if considered needed by Sponsor on the basis of the emerging 
data. Every 4 weeks ( 3 days) in the first 12 weeks post-final dose, then every 12 weeks 
( 7 days). 
* For Part 1b, all participants will stay at the clinic overnight on Day 1 after each dose. Optional 
overnight stay at the clinic on Day 2 and Day 3 after the first dose, i.e., on Day 2 and Day 3, 
participants can either stay at the clinic overnight or can be discharged after completion of the 
assessments and return the next morning for the subsequent assessments, at the 
Investigator’s discretion.  
For all cohorts in Part 2a and Cohorts 1 and 2 in Part 2b, all participants will stay at the clinic 
for at least 8 hours postdose for safety observation and sample collection. The overnight stay 
from Day 1 to Day 4 for sample collection and assessment is optional, at the Investigator’s 
discretion.  
For Cohorts 3 and 4 in Part 2b, all participants will stay at the clinic overnight on Day 1. The 
overnight stay on Day 2 and Day 3 for sample collection and assessment is optional, at the 
Investigator’s discretion.  

 
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For Part 3, all participants will stay at the clinic for at least 8 hours after each dose for safety 
observation and sample collection. Overnight stay at the clinic on Day 1 after each dose and 
on Days 2 and 3 after the first dose is optional. 
** Participants can stay at clinic the night before Day 1 (i.e., Day 1) if site prefers due to logistic 
reasons. 
*** After completing the scheduled visits, an additional ADA and PK sample collection may be 
needed, depending on the emerging ADA data. 
 
4.4 
END OF STUDY DEFINITION 
A participant is considered to have completed the study if the participant completed all 
phases of the study including the last visit. 
The end of the study is defined as the date when the last participant last observation 
(LPLO) occurs. Due to the exploratory nature of the trial, this study can be discontinued 
before all cohorts have been investigated. This will not constitute a premature 
discontinuation of the study. 

 
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5. 
STUDY POPULATION 
The study population rationale is provided in Section 4.2.1. 
The participants in this study will be female and male healthy participants (Part 1) or 
virologically suppressed patients with CHB (Parts 2 and 3), between 18 and 65 years of 
age, inclusive, who fulfill all of the given inclusion criteria and none of the exclusion 
criteria. 
Prospective approval of protocol deviations, also known as protocol waivers or 
exemptions, is not permitted. All eligibility decisions are made by the Investigator. The 
Medical Monitor is available to the Investigator to answer any medical questions. 
5.1 
INCLUSION CRITERIA AND EXCLUSION CRITERIA FOR 
PART 1 (HEALTHY PARTICIPANTS) 
5.1.1 
Inclusion Criteria for Part 1 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
Informed Consent 
1. 
Able and willing to provide written informed consent and to comply with the study 
protocol according to International Council for Harmonisation (ICH) and local 
regulations. 
 
Age 
2. 
Male and female participants 18 to 65 years of age (inclusive), at the time of signing 
the Informed Consent Form (ICF). 
 
Ethnicity 
3. 
Cohort 6 only: Chinese male and female participants. A Chinese subject is defined 
as his/her biological parents and grandparents are of Chinese ethnicity. 
 
Type of Participants and Disease Characteristics 
4. 
Healthy participants where the status is defined by absence of evidence of any 
active or chronic disease following a detailed medical and surgical history, a 
complete physical examination including vital signs, 12-lead ECG, hematology, 
clinical chemistry, serology, coagulation, and urinalysis. 
 
Weight 
5. 
A body mass index (BMI) between 18 and 32 kg/m2, inclusive. 
 

 
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Sex and Contraception/Barrier Requirements 
6. 
Biological Male and/or Female Participants 
The reliability of sexual abstinence for the eligibility and enrollment of all participants 
needs to be evaluated in relation to the duration of the clinical study and the preferred 
and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods. 
a. 
Biological Female Participants 
Biological female participants are eligible to participate if they are not pregnant (see 
Appendix 5), not breastfeeding, and at least one of the following conditions applies: 
 
Participants of non-childbearing potential (PONCBP), as defined in Appendix 5. 
 
Participant of childbearing potential (POCBP), who: 
o Agree to remain abstinent (refrain from heterosexual intercourse) or use at least 
one highly effective contraceptive method that results in a failure rate of  1% per 
year until 24 weeks after final dose of study treatment. Examples of contraceptive 
methods with a failure rate of  1% are in Appendix 5. The Investigator should 
evaluate with the participant the best contraceptive method based on anatomy 
and physiology, and lifestyle considerations when possible. 
o Have a negative pregnancy test (blood) within 28 days prior to the first study 
treatment administration. 
 
b. 
Biological Male Participants 
No contraception measures are needed. 
 
5.1.2 
Exclusion Criteria for Part 1 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. 
Pregnant (positive pregnancy test) or lactating women 
2. 
Current infection with hepatitis A virus (HAV), HBV, hepatitis C virus (HCV), or HIV 
3. 
History of any clinically significant gastrointestinal, renal, hepatic, 
bronchopulmonary, neurological, psychiatric, cardiovascular, endocrinological, 
hematological, or allergic disease, metabolic disorder, cancer, or cirrhosis 
4. 
History of immunologically mediated disease (e.g., inflammatory bowel disease, 
idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic 
anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or 
any other autoimmune disease) 
5. 
Concomitant disease or condition that could interfere with, or treatment of which 
might interfere with, the conduct of the study, or would, in the opinion of the 
Investigator, pose an unacceptable risk to the participant in this study, including but 

 
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not limited to any major illness within 1 month prior to screening or any febrile illness 
within 1 week prior to screening and up to study treatment administration 
6. 
History or presence of clinically significant ECG abnormalities based on the average 
of the triplicate ECG recordings (e.g., PQ/PR interval  210 ms, QT corrected for 
heart rate using the Fridericia’s correction factor [QTcF]  450 ms for males and 
QTcF  470 ms for females) or cardiovascular disease (e.g., cardiac insufficiency, 
coronary artery disease, cardiomyopathy, congestive heart failure, family history of 
congenital long QT syndrome, family history of sudden death) 
 
Prior/Concomitant Therapy 
7. 
Use of any prescription drugs, herbal supplements, and/or over-the-counter (OTC) 
medication or dietary supplements (vitamins included) within the 2 weeks prior to 
the first dosing or within 5 half-lives of the medication prior to first dosing (whichever 
is longer). Vaccination is prohibited between 2 weeks before and 1 week after a 
dose of RO7565020. 
 
Prior/Concurrent Clinical Study Experience 
8. 
Are currently enrolled in, have participated in, or plan to participate in any other 
clinical study involving an investigational medicinal product (IMP) or medical device 
from within the last 90 days prior to screening or within 5 times the elimination half-
life if known (whichever is longer) until completion of the follow-up visit. 
 
Diagnostic Assessments 
9. 
Confirmed (see Section 8.2.2) systolic blood pressure (SBP) greater than 140 or 
less than 90 mmHg, or diastolic blood pressure (DBP) greater than 90 or less than 
50 mmHg, at screening 
10. Clinically significant abnormalities (as judged by the Investigator) in laboratory test 
results (including complete blood count, chemistry panel, and urinalysis). In case of 
uncertain or questionable results, tests performed during screening may be 
repeated once to confirm eligibility prior to enrollment. 
11. Evidence of HIV infection and/or positive result for human HIV antibodies 
12. Presence of HBsAg, or positive HAV Ab IgM or positive HCV RNA test results at 
screening 
13. Any suspicion or history of alcohol abuse (consumption of more than 2 standard 
drinks per day on average; 1 standard drink = 10 g alcohol) and/or any history or 
suspicion of regular consumption/addiction or drug abuse within 2 years prior to 
study treatment administration or a positive drug-screening test 
14. Active smokers or use of tobacco and/or nicotine-containing products in the 
previous 3 months prior to screening. Urine cotinine levels will be measured 
at screening and on Day 1 for all participants. Smokers will be defined as any 
participant who reports tobacco use and/or who has a positive urine cotinine test. 
 

 
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Other Exclusions 
15. Donation or loss of blood over 500 mL, or administration of any blood product, within 
90 days prior to study treatment administration 
16. Any clinically significant history of hypersensitivity or allergic reactions, either 
spontaneous or following study treatment administration, or exposure to food or 
environmental agents 
17. History of hypersensitivity to any of the excipients (i.e., polysorbate 80, D-sucrose, 
and L-methionine) in the formulation of RO7565020 
18. Participants under judicial supervision, guardianship, or curatorship 
19. Participants who, in the opinion of the Investigator, should not participate in this 
study. 
20. Participants with insufficient venous access 
 
5.2 
INCLUSION CRITERIA AND EXCLUSION CRITERIA FOR 
PARTS 2 AND 3 (PARTICIPANTS WITH CHB) 
5.2.1 
Inclusion Criteria for Parts 2 and 3 
Participants are eligible to be included in Parts 2a, 2b, or 3 of the study only if all of the 
following criteria apply: 
Informed Consent 
1. 
Able and willing to provide written informed consent and to comply with the study 
protocol according to ICH and local regulations 
 
Age 
2. 
Participants must be between 18 and 65 years of age, inclusive, at the time of 
signing the ICF. 
 
Type of Participants and Disease Characteristics 
3. 
CHB infection (HBsAg-positive for  6 months) 
a) On NUC (ETV, TAF, or TDF) monotherapy (per local prescription information) 
for  12 months. Patients must be on the same NUC therapy for at least 
3 months before screening. 
b) HBV DNA below the lower limit of quantification (LLOQ) or  10 IU/mL for 
 6 months prior to screening and confirmed at screening. 
c) 
ALT  1.5  upper limit of normal (ULN) for  6 months prior to screening and 
confirmed at screening. Total bilirubin within normal range at screening 
(isolated elevated bilirubin  1.5  ULN is acceptable for participants with Gilbert 
syndrome) 

 
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4. 
HBsAg titer at screening:  
Part 2a: 20 IU/mL  HBsAg 3000 IU/mL 
Part 2b: HBsAg 3000 IU/mL ( 10,000 IU/mL in Cohort 1 and Cohort 2, and first 
2 participants in Cohort 3 and Cohort 4) 
5. 
Screening laboratory values (hematology, chemistry, urinalysis) within normal 
ranges or judged not clinically significant by the Investigator 
6. 
Liver biopsy, FibroScan, or equivalent test obtained within the past 6 months 
demonstrating liver disease consistent with chronic HBV infection without evidence 
of bridging fibrosis or cirrhosis (Metavir score  3, recommended cutoff for 
FibroScan 8.5 kPa) 
 
Weight 
7. 
BMI between 18 and 32 kg/m2, inclusive 
 
Sex and Contraception/Barrier Requirements 
8. 
Biological Male and/or Female Participants 
The reliability of sexual abstinence for the eligibility and enrollment of all participants 
needs to be evaluated in relation to the duration of the clinical study and the preferred 
and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, 
symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods. 
a. 
Biological Female Participants 
Biological female participants are eligible to participate if they are not pregnant (see 
Appendix 5), not breastfeeding, and at least one of the following conditions applies: 
 
PONCBP, as defined in Appendix 5. 
 
POCBP, who: 
o Agree to remain abstinent (refrain from heterosexual intercourse) or use of at 
least one highly effective contraceptive method that results in a failure rate of 
 1% per year until 24 weeks after final dose of study treatment. Examples of 
contraceptive methods with a failure rate of  1% are in Appendix 5. The 
Investigator should evaluate with the participant the best contraceptive method 
based on anatomy and physiology, and lifestyle considerations when possible. 
o Have a negative pregnancy test (blood) within 28 days prior to the first study 
treatment administration. 
 
b. 
Biological Male Participants 
No contraception measures are needed. 
 

 
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5.2.2 
Exclusion Criteria for Parts 2 and 3 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. 
Pregnant (positive pregnancy test) or lactating women 
2. 
Anti-HBs antibody positive at screening 
3. 
Current co-infection with other pathogens such as HAV, HCV, hepatitis D virus 
(HDV), hepatitis E virus (HEV), or HIV 
4. 
Evidence of liver cirrhosis or decompensated liver disease such as ascites, 
esophageal or gastric varices, splenomegaly, nodular liver, jaundice, hepatic 
encephalopathy, or portal hypertension 
5. 
History of or suspicion of HCC (e.g., elevated -fetoprotein [AFP] levels, or 
suggestive lesions on abdominal ultrasound or other imaging) 
6. 
History or other evidence of a medical condition associated with chronic liver 
disease other than HBV infection (e.g., hemochromatosis, autoimmune hepatitis, 
alcoholic liver disease, toxin exposure, thalassemia, nonalcoholic steatohepatitis, 
metabolic liver disease) 
7. 
Expected to need systemic antiviral therapy other than that provided by the study at 
any time during their participation in the study, with the exception of oral/ topical 
therapy for HSV I or HSV II 
8. 
History of immunologically mediated disease (e.g., inflammatory bowel disease, 
idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic 
anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or 
any other autoimmune disease) 
9. 
History of clinically significant and not adequately controlled cardiovascular, 
endocrine, gastrointestinal, renal, ocular, pulmonary, or neurological disease 
10. History of clinically significant psychiatric disease 
11. Evidence of an active or suspected cancer or a history of malignancy other than 
adequately treated basal cell carcinoma 
12. History of having received or currently receiving any systemic anti-neoplastic 
(including radiation) or immune-modulatory treatment (including systemic oral or 
inhaled corticosteroids, IFN or PEG-IFN) within the 8 weeks prior to the first dose of 
study treatment or the expectation that such treatment will be needed at any time 
during the study. Eye drop-containing, topical, and infrequent inhaled corticosteroids 
are permissible up to 4 weeks prior to the first dose of study treatment. 
13. History of alcohol abuse (consumption of more than 2 standard drinks per day on 
average; 1 standard drink = 10 g alcohol) and/or drug abuse within 1 year prior to 
study Day 1 
14. Currently taking, or have received within 3 months of Day 1, systemic 
corticosteroids at a high dose (e.g., 40 mg prednisolone per day) for  7 days, or a 
low dose (e.g., 20 mg prednisolone per day) for  14 days 

 
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15. History of organ transplantation 
16. Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any 
drug, or multiple drug allergies (non-active hay fever is acceptable) 
17. Significant acute infection (e.g., influenza, COVID-19, local infection) or any other 
clinically significant illness within 2 weeks prior to study Day 1 
18. Donation or loss of blood over 500 mL, or administration of any blood product, within 
90 days prior to study treatment administration 
 
Prior/Concomitant Therapy 
19. Unable to comply with any drugs or nutrients listed in prohibited therapies 
(Section 6.5.2.2). Vaccination is prohibited between 2 weeks before and 1 week 
after a dose of RO7565020. 
 
Prior/Concurrent Clinical Study Experience 
20. Are currently enrolled in, have participated in, or plan to participate any other clinical 
study involving an IMP or medical device study from within the last 90 days prior to 
screening or within 5 times the elimination half-life if known (whichever is longer) 
until completion of the Follow-up visit. 
 
Diagnostic Assessments 
21. One or more of the following laboratory abnormalities at screening: 
a) Hemoglobin  LLN; platelets  LLN; INR  1.1 × ULN 
b) Total serum bilirubin  ULN (or  1.5 x ULN for participants with Gilbert 
syndrome) 
c) 
Serum albumin  LLN 
d) Positive results for antimitochondrial antibodies (AMA  1:80), antinuclear 
antibody (ANA  1:80), anti-smooth muscle antibody (ASMA  1:40), or 
anti-thyroperoxidase antibodies (a-TPO  ULN) 
e) Abnormal thyroid-stimulating hormone (TSH) 
f) 
White blood cell count  2500 cells/μL; neutrophil count  1500 cells/μL 
( 1200 cell/μL if considered a physiological variant in a patient of African 
descent) 
g) Positive test for drugs of abuse and/or positive alcohol test at screening. For 
positive cannabinoids test, the eligibility is at the Investigator’s discretion. 
22. ECG at screening with clinically significant abnormalities, including QT corrected 
using Fridericia’s formula (QTcF) interval  450 ms for males and  470 ms for 
females 
23. Abnormal renal function including serum creatinine  ULN or calculated creatinine 
clearance  70 mL/min (using the Cockcroft Gault formula) 
 

 
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Other Exclusions 
24. History of intolerance to IV or SC injection 
25. History of hypersensitivity to any of the excipients (i.e., polysorbate 80, D-sucrose, 
and L-methionine) in the formulation of RO7565020 
26. Participants under judicial supervision, guardianship, or curatorship 
27. Medical or social conditions that would potentially interfere with the participant’s 
ability to comply with the study visit schedule or the study assessments 
 
5.3 
LIFESTYLE CONSIDERATIONS 
Participants are expected to follow protocol requirements for contraception. There are no 
other lifestyle restrictions during the study. 
5.3.1 
Meals and Dietary Restrictions 
There are no study-specific restrictions to meals and dietary requirements. 
5.3.2 
Caffeine, Alcohol, and Tobacco 
The consumption of foods and beverages containing methylxanthines (e.g., tea, coffee 
and caffeinated soft drinks) will not be permitted 8 hours before study treatment 
administration, during the in-clinical period and 8 hours before each of the ambulatory 
visits, and will be restricted to a maximum of three cups of coffee or tea per day and 1 L 
per day of methylxanthine-containing drinks (e.g., cola) during the out-clinic time until 
follow-up. 
Consumption of alcohol will not be allowed 48 hours before study drug administration 
and while resident in the clinical unit and 48 hours before each of the ambulatory visits 
and should be limited to a maximum of 2 units/day (1 unit = 10 mL of pure alcohol) 
during the out-clinic period until follow-up. 
5.3.3 
Activity 
Participants are strongly recommended not to have intense physical activity 96 hours 
before each blood collection for clinical laboratory tests during the study. 
5.4 
SCREEN FAILURES 
Screen failures are defined as participants who consent to participate in the study but 
are not subsequently randomized to study treatment (Part 1) or entered in the study 
(Parts 2 and 3). Screen failures may be tracked separately. 
The Investigator will maintain a screening log to record details of all participants 
screened and to confirm eligibility or record reasons for screening failure. 
If a subject fails an inclusion/exclusion criterion due to a transient and non-clinically 
significant condition at screening, the Investigator may repeat the relevant screening 

 
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assessment(s) within the screening period (28 days for Part 1 and 56 days for Parts 2 
and 3). If the subject fails a second time, they will be classed as a screen failure. 
Re-screening is allowed for participants who were screened in the study and met study 
inclusion/exclusion criteria but failed to be enrolled within 28 days (Part 1) or 56 days 
(Parts 2 and 3) after the start of screening period because of an administrative reason 
(e.g., study halt, or logistical, personal, or technical reasons). Re-screening is also 
allowed for participants who failed screening because of a transient illness 
(e.g., influenza or COVID-19 infection). To re-screen such a participant, all inclusion 
and exclusion criteria need to be re-evaluated and all applicable screening assessments 
repeated if done more than 28 days (Part 1) or 56 days (Parts 2 and 3) before 
enrollment. In addition, for Parts 2 and 3, the blood chemistry and pregnancy tests need 
to be done within 14 days before Day 1. 
The patients who have failed the screening due to HBsAg level (e.g., not met the 
criterion of  3000 IU/mL in Part 2a, or not  3000 IU/mL in Part 2b, or above the upper 
limit of 10,000 IU/mL in Part 2b Cohorts 1 and 2) can be re-screened for other patients’ 
parts or cohorts in this study. To re-screen such patients, all inclusion and exclusion 
criteria need to be re-evaluated and all applicable screening assessments repeated if 
done more than 56 days before Day 1 (the blood chemistry and pregnancy tests need to 
be done within 14 days). 
For Part 2b Cohort 3 and Cohort 4, dosing of participants with HBsAg  10,000 IU/mL at 
screening will be on hold until at least 2 participants with 3000 IU/mL < HBsAg 
≤ 10,000IU/mL have been dosed and confirmed safety by 28-day follow-up. All inclusion 
and exclusion criteria of these participants need to be re-evaluated before dosing. The 
applicable screening assessments need to be repeated if done more than 56 days 
before Day 1 (the blood chemistry and pregnancy tests need to be done within 14 days). 
For re-screening, there is no need to repeat liver biopsy or transient elastography/ 
acoustic radiation force impulse (ARFI)/magnetic resonance imaging (MRI) assessment 
if done within 6 months and reliably documented. 
In case of uncertain or questionable results, any of the tests performed during screening 
may be repeated once before study treatment administration to confirm eligibility or 
clinical significance. 
5.5 
RECRUITMENT PROCEDURES 
Participants will be identified for potential recruitment using pre-screening enrollment 
logs, clinical database and IEC/IRB-approved newspaper/radio/social-media 
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6. 
TREATMENTS 
Study treatment is defined as any investigational product (including placebo) or 
marketed product intended to be administered to a study participant according to the 
study protocol. 
The IMP for this study is RO7565020, an HBsAg mAb. NUCs (ETV, TDF, and TAF), as 
background treatment, are classified as authorized auxiliary medicinal products 
(AxMPs)/non-investigational medicinal products (NIMPs). Appendix 6 identifies all 
investigational and non-investigational medicinal products for this study. RO7565020 
administrations will be at the study center under supervision of site staff. NUCs will be 
self-administered by participants. 
Cases of accidental overdose or medication error, along with any associated AEs, 
should be reported as described in Appendix 2, Section 5.2. 
6.1 
TREATMENTS ADMINISTERED 
The treatments administered are summarized in Table 8. Guidelines for treatment 
interruption or discontinuation are provided in Section 6.6.1 or Section 7, respectively. 
Please see RO7565020 IB and the pharmacy manuals for more details. 
Table 8 
Summary of Treatments Administered 
Study treatment 
name: 
RO7565020 
Placebo 
NUC 
(ETV, TAF, or TDF) 
Use: 
Experimental 
Placebo comparator 
Background treatment 
Dose formulation: 
Vial 
Vial 
Refer to local 
prescribing 
information. 
Unit dose strength(s): 
360 mg/2 mL 
0 mg/20 mL 
Dose and regimen: 
See details in Table 6 
Not applicable 
Route of 
administration: 
SC injection/ 
IV infusion 
SC injection/ 
IV infusion 
Oral 
Source: 
Provided centrally by 
the Sponsor. 
Provided centrally by 
the Sponsor. 
Continued as 
prescribed by the 
treating physician, 
can be provided 
centrally or locally. 
Packaging and 
labeling: 
Study treatment will 
be provided in a 2 mL 
glass vial. Each vial 
will be labeled as 
required per country 
requirement. 
Placebo will be 
provided in a 
single-dose 20 mL 
glass vial. 
Study treatment will be 
packaged and labeled 
if required per local 
regulation. 
Abbreviations: ETV = entecavir; IV = intravenous; NUC = nucleos(t)ide analogue; 
SC = subcutaneous; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil fumarate. 
  

 
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6.2 
PREPARATION, HANDLING, STORAGE, AND 
ACCOUNTABILITY 
The packaging and labeling of the IMP will be done in accordance with the Sponsor’s 
standard and local regulations. IMP packaging will be overseen by the Sponsor’s clinical 
study supplies department and bear a label with the identification required by local law, 
the protocol number, drug identification, and dosage.  
The study site must follow all instructions included with each shipment of IMP. The 
Investigator or other authorized personnel (e.g., pharmacist) will acknowledge receipt of 
study treatment and confirm the shipment condition and content. Any damaged 
shipments will be replaced. The Investigator or designee must confirm that appropriate 
temperature conditions have been maintained during transit for all IMP received and that 
any findings, product complaints, or discrepancies have been reported and resolved 
before use of the IMP. All IMP must be stored in a secure, environmentally controlled, 
and monitored (manual or automated) area in accordance with the labeled storage 
conditions, with access limited to the Investigator and authorized staff. 
Only participants enrolled in the study may receive IMP, and only authorized staff may 
supply or administer IMP. 
The Investigator is responsible for IMP accountability (i.e., receipt, reconciliation, and 
final disposition records). The authorized study personnel [e.g., pharmacist]) will 
maintain records of IMP delivery to the site, IMP inventory at the site, study treatment 
use by each participant, disposition or return of unused IMP. This will enable 
reconciliation of all IMP received, and ensure that participants are provided with the 
doses which are specified in the protocol. 
IMP will either be disposed of at the study site according to the study site’s institutional 
standard operating procedure (SOP) or returned to the Sponsor with the appropriate 
documentation. Local or institutional regulations may require immediate destruction of 
used IMP for safety reasons. The site must obtain written authorization from the Sponsor 
before any IMP is destroyed, and IMP destruction must be documented on the 
appropriate form. Accurate records of all IMP received at, dispensed from, returned to, 
and disposed of by the study site will be recorded on the drug accountability log. 
Refer to the pharmacy manual for information on study treatment formulation, study 
treatment handling (including preparation and storage), and accountability. 
6.3 
MEASURES TO MINIMIZE BIAS: RANDOMIZATION AND 
BLINDING 
6.3.1 
Method of Treatment Assignment 
Participants in each cohort of Part 1a and Part 1b will be randomized to active treatment 
or placebo. The list of randomized treatment assignments will be generated by the 
Sponsor or its designee. The randomized treatment assignment will be allocated from 

 
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the list sequentially to subjects in the order in which they are randomized. For each dose 
cohort in Part 1a and Part 1b, the randomization will be designed such that of the first 
2 participants, 1 will receive active drug and the other will receive placebo. The 
remaining 6 participants in the cohort will be randomized such that 5 receive active drug 
and 1 receives placebo. The treatment allocation will be managed by the unblinded 
pharmacist and will be based on the randomization code list. 
Parts 2 and 3 are open label and participants will all receive active treatment. The 
specific treatment to be taken by a participant will be assigned using interactive 
(voice/web) response system (IxRS), according to specifications provided by the 
Sponsor to the external vendor. The site will contact the IxRS prior to the start of study 
treatment administration for each participant. The site will record the treatment 
assignment on the applicable electronic case report form (eCRF), if required. 
6.3.2 
Blinding 
In each cohort of Part 1a and Part 1b, participants will be randomized to RO7565020 or 
placebo. The randomization numbers will be generated by the Sponsor or its designee. 
The study is observer-blind. This means that in the randomized cohorts (i.e., cohorts in 
Part 1a and Part 1b), the participant, the Investigator(s), and all individuals in direct 
contact with the participant at the investigative site will be blinded, except the pharmacist 
handling the study treatment and the unblinded study treatment administrator (if deemed 
necessary). 
To allow informed recommendations or decisions regarding dose-selection in this study, 
an integrated assessment of the safety and tolerability data and available PK data will be 
made prior to each dose-escalation decision. The Clinical Pharmacologist, Clinical 
Scientist, Safety Science Lead, and the Clinical Biomarker Lead who perform this 
assessment, together with the Biostatistician, Data Acquisition Specialist, and 
Clinical/Statistical Programmer will be unblinded with regard to the treatment allocation 
of participants. PK/PD data can be received and cleaned on an ongoing basis. The data 
will be handled and cleaned in a secure area which is not accessible by any blinded 
study management team member. Likewise, the Bioanalyst and the Pharmacometrician 
will be unblinded. Other members of the Sponsor’s project and study teams who do not 
have any direct contact with the participants may be unblinded at the Clinical 
Pharmacologist’s discretion. The Clinical Pharmacologist or Clinical Pharmacology 
Scientist may share aggregated reports (e.g., tabular summaries or mean graphs by 
treatment group) with other individuals (e.g., Principal Investigator) who are involved in 
the dose decision process, but should not disclose individual treatment assignment. 
Investigators will remain blinded to each participant’s assigned study treatment 
throughout the course of the study. To maintain this blind, an otherwise uninvolved 
unblinded pharmacist will be responsible for the reconstitution and dispensation of all 
study treatment and an otherwise uninvolved unblinded study treatment administrator 
will be responsible for the study treatment administration, if deemed necessary. In the 

 
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event of a quality assurance audit, the auditor(s) will be allowed access to unblinded 
study treatment records at the site(s) to verify that randomization/dispensing has been 
done accurately. 
A sealed envelope that contains the treatment assignment for each participant will be 
provided to the Investigator. The sealed envelope will be retained by the Investigator (or 
representative) in a secured area. Once the study is complete, all envelopes (sealed and 
opened) must be inventoried and returned to the Sponsor. 
If the Investigator wishes to know the identity of the study treatment for any reason other 
than a medical emergency, he/she should contact the Medical Monitor directly. The 
Investigator should document and provide an explanation for any non-emergency 
unblinding. 
The Sponsor must be notified before the blind is broken unless identification of the study 
treatment is required for medical emergency in which the knowledge of the specific 
blinded treatment will affect the immediate management of the participant’s conditions 
(e.g., antidote is available). In this case, the Sponsor must be notified within 24 hours 
after breaking the blind. The date and reason that the blind was broken must be 
recorded in the source documentation and eCRF, as applicable. 
As per Health Authority reporting requirements, the Sponsor's drug safety representative 
will break the treatment code for all serious, unexpected suspected adverse reactions 
(see Appendix 2) that are considered by the Investigator or Sponsor to be related to 
study treatment. The participant may continue to receive treatment, and the Investigator, 
participant, and the blinded Sponsor personnel as specified in the treatment assignment 
information dissemination form, with the exception of the drug safety representative and 
personnel who must have access to participant treatment assignments to fulfill their roles 
(as defined above), will remain blinded to treatment assignment. 
Whenever disclosure of the identity of the test medication is necessary, adequate 
procedures will be in place to ensure integrity of the data. Any unblinding will be 
documented in the study report with date, reason for identifying the drug and the 
name(s) and role(s) in the study of the person(s) unblinded. 
Parts 2 and 3 are open label; blinding procedures are not applicable. 
6.4 
TREATMENT COMPLIANCE 
The qualified individual responsible for dispensing the study treatment will prepare the 
correct dose according to the randomization schedule. This individual will write the date 
dispensed and participant number on the study treatment vial label and on the Drug 
Accountability Record. This individual will also record the study treatment number 
received by each participant during the study. 

 
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6.5 
CONCOMITANT THERAPY 
Any medication or vaccine (including OTC or prescription medicines, approved dietary 
and herbal supplements, nutritional supplements) used by a participant from 30 days 
prior to screening until the follow-up visit must be recorded along with reason for use, 
dates of administration (including start and end dates) and dosage information (including 
dose and frequency). 
The Medical Monitor should be contacted for advice if there are any questions regarding 
concomitant or prior therapy. 
All concomitant medications should be reported to the Investigator and recorded on the 
Concomitant Medications eCRF. 
All medication administered to manage AEs should be recorded on the Adverse Event 
eCRF. 
6.5.1 
Concomitant Medications for Part 1 
6.5.1.1 
Permitted Therapy for Part 1 
Participants who use oral contraceptives, hormone-replacement therapy, or other 
maintenance therapy should continue their use. 
Paracetamol/Acetaminophen at doses of  2 g/day is permitted for use any time during 
the study. 
6.5.1.2 
Prohibited Therapy for Part 1 
As a general rule, no other concomitant medication will be permitted, with the exception 
of medications to treat AEs, unless the rationale for exception is discussed and clearly 
documented between the Investigator and the Sponsor. 
Participants should avoid taking prescription and non-prescription drugs (including 
vitamins and dietary or herbal supplements) within 2 weeks or 5 half-lives (whichever is 
longer) before the start of study treatment until completion of the follow-up visit, unless, 
in the opinion of the Investigator and Sponsor, the medication will not interfere with the 
study. 
Vaccination is prohibited between 2 weeks before and 1 week after a dose of 
RO7565020. 
6.5.2 
Concomitant Medications for Parts 2 and 3 
6.5.2.1 
Permitted Therapy for Parts 2 and 3 
Participants who use oral contraceptives, hormone-replacement therapy, or other 
maintenance therapy should continue their use. 

 
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Paracetamol/Acetaminophen at doses of  2 g/day is permitted for use any time during 
the study.  
Other concomitant medication may be considered on a case-by-case basis by the 
Investigator in consultation with the Sponsor’s Clinical Pharmacologist and Medical 
Monitor. 
6.5.2.2 
Prohibited Therapy for Parts 2 and 3 
Use of the following therapies is prohibited (with the exception of medications to treat 
AEs), unless otherwise specified below, or the rationale for exception is discussed and 
clearly documented between the Investigator and the Sponsor. 
 
Any systemic anti-neoplastic (including radiation) or immune-modulatory treatment 
(including systemic oral or inhaled corticosteroids, IFN or PEG-IFN) is prohibited at 
any time during the study and for at least 8 weeks prior to the first dose of study 
treatment. Eye drop-containing, topical, and infrequent inhaled corticosteroids are 
permissible up to 4 weeks. 
 
Any systemic antiviral therapy other than NUC (with the exception of oral therapy for 
HSV I or HSV II) is prohibited at any time during the study.  
 
Participants should avoid taking non-prescription drugs (including vitamins and dietary or 
herbal supplements) within 2 weeks or 5 half-lives (whichever is longer) before the start 
of study treatment until completion of the follow-up visit, unless, in the opinion of the 
Investigator and Sponsor, the medication will not interfere with the study. 
Vaccination is prohibited between 2 weeks before and 1 week after a dose of 
RO7565020. 
Participants should follow the NUC prescribing information with respect to concomitant 
medication use while taking the NUC. 
6.6 
DOSE MODIFICATION AND TEMPORARY INTERRUPTION 
In general, there will be no dose modifications for RO7565020 in this study. 
6.6.1 
Temporary Interruption 
Before permanently discontinuing study treatment (regardless of whether initiated by the 
participant, Investigator, or Sponsor), an interruption of study treatment should be 
considered. Participants who have temporarily interrupted study treatment should restart 
it as soon as medically justified in the opinion of the Investigator. 

 
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6.7 
TREATMENT AFTER THE END OF THE STUDY 
Currently, the Sponsor does not intend to provide RO7565020 or NUC to participants 
after conclusion of the study or any earlier participant withdrawal. 
The Sponsor will evaluate whether to continue to provide RO7565020 or NUC to 
participants after the main study is over, in accordance with the Roche Global Policy on 
Continued Access to Investigational Medicinal Product, available at the following 
website: 
http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf 

 
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7. 
DISCONTINUATION OF STUDY, STUDY TREATMENT, AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
An excessive rate of participant withdrawals (either participants discontinuing study 
treatment or withdrawing from the study) can render the study non-interpretable. 
Therefore, unnecessary withdrawal of participants should be avoided and efforts should 
be taken to motivate participants to comply with all the study-specific procedures as 
outlined in this protocol. 
Details on study and site closures are provided in Appendix 1, Section 4. 
7.1 
DISCONTINUATION OF STUDY TREATMENT 
Reasons for discontinuation of study treatment RO7565020 may include, but are not 
limited to, the following: 
 
Participant withdrawal of consent at any time. 
 
Any medical condition that the Investigator or Sponsor determines may jeopardize 
the participant’s safety if he or she continues in the study. 
 
Investigator or Sponsor determination that treatment discontinuation is in the best 
interest of the participant. 
 
Pregnancy. 
 
Any other event that meets individual stopping criteria defined in Section 4.1.1.3.2. 
 
Safety and tolerability issues, e.g., acute reactions, not tolerable and not 
manageable with symptomatic treatment. 
 
For Parts 2 and 3 only: 
 
Disease progression, e.g., any sign of development of liver cirrhosis (or liver 
imaging indicating cirrhosis), decompensation (e.g., ascites, variceal hemorrhage, 
Child-Pugh Class B or C clinical classification), or HCC 
 
Grade 4 ALT abnormal (i.e.,  10  ULN) as defined by the DAIDS Table for Grading 
the Severity of Adult and Pediatric Adverse Events (DAIDS AE grading table) 
confirmed within 48 to 72 hours 
 
Grade 3 ALT abnormal (i.e.,  5  to  10  ULN) combined with total 
bilirubin  2  ULN (of which  35% is direct bilirubin), or Grade 3 ALT abnormal and 
INR  1.5 
 
Every effort should be made to obtain information on a participant who withdraws from 
the study treatment but has not withdrawn consent. A participant who discontinues study 
treatment prematurely will be asked to return to the clinic for a study completion/early 
termination visit (see Section 8.11.3) and may undergo follow-up assessments (see 
Section 8.11.4), unless the participant has withdrawn consent. The primary reason for 
premature study treatment discontinuation should be documented on the appropriate 
eCRF. Participants who discontinue study treatment prematurely due to safety reasons 

 
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will not be replaced. Participants who discontinue study treatment prematurely due to 
other reasons may be replaced.  
7.2 
PARTICIPANT DISCONTINUATION OR WITHDRAWAL FROM 
THE STUDY 
Participants have the right to voluntarily withdraw from the study at any time for any 
reason and without justification. 
In addition, the Investigator can discontinue a participant from the study for medical 
conditions that the Investigator or Sponsor determines may jeopardize the participant’s 
safety if the participant continues in the study. 
If possible, information on the reason for withdrawal from the study should be obtained. 
The primary reason for withdrawal from the study should be documented on the 
appropriate eCRF. Participants will not be followed up with for any reason after consent 
has been withdrawn. This includes the follow-up assessments. 
When a participant voluntarily withdraws from the study, or is discontinued by the 
Investigator, samples collected until the date of withdrawal/discontinuation will be 
analyzed, unless the participant specifically requests for these to be discarded or local 
laws require their immediate destruction. However, if samples have been tested prior to 
withdrawal, results from those tests will be used as part of the overall research data. A 
participant's withdrawal from this study does not, by itself, constitute withdrawal of 
samples donated to the Research Biosample Repository (RBR). 
Participants who withdraw from the study for safety reasons will not be replaced. 
Participants who withdraw from the study for other reasons may be replaced. 
For data to be collected at the time of study discontinuation and any further evaluations 
that need to be completed, see the SoA (Section 1.3). 
7.3 
LOST TO FOLLOW-UP 
A participant will be considered lost to follow-up if the participant repeatedly fails to 
return for scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
 
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 
 
Before a participant is deemed lost to follow-up, the Investigator or designee must 
make every effort to regain contact with the participant. These contact attempts 
should be documented in the participant’s medical record. 

 
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 
Should the participant continue to be unreachable, the participant will be considered 
to have withdrawn from the study. 
Discontinuation of sites or of study as a whole are handled as part of Appendix 1. 

 
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8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timepoints are summarized in the SoA (Section 1.3). 
Prospective approval of protocol deviations, also known as protocol waivers or 
exemptions, is not permitted. 
Immediate safety concerns should be discussed with the Sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study treatment. 
Procedures conducted as part of the participant’s routine clinical management 
(e.g., blood count) and obtained before signing of the ICF may be utilized for screening 
or baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the timeframe defined in the SoA. 
Repeat or unscheduled samples may be taken for safety reasons or technical issues 
with the samples. 
8.1 
EFFICACY ASSESSMENTS 
Efficacy assessments are not applicable for this study. 
8.2 
SAFETY ASSESSMENTS 
Planned timepoints for all safety assessments are provided in the SoA (Section 1.3). 
Safety assessments will consist of monitoring and recording AEs, including SAEs and 
AEs of special interest (AESI); measurement of protocol-specified safety laboratory 
assessments; measurement of protocol-specified vital signs, ECGs; and other protocol-
specified tests that are deemed critical to the safety evaluation of the study. 
8.2.1 
Physical Examinations 
A complete physical examination should be performed at screening and will include, at a 
minimum, assessments of the cardiovascular, respiratory, gastrointestinal, 
dermatological, neurological, and musculoskeletal systems in addition to the head, eyes, 
ears, nose, throat, neck, and lymph nodes. Height and weight will also be measured and 
recorded. Further examination of other body systems may be performed in case of 
evocative symptoms at the Investigator’s discretion. 
At subsequent visits (or as clinically indicated), symptom-directed physical examinations 
should be performed. Weight will also be measured and recorded according to SoA 
(Section 1.3). 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 

 
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Any abnormality identified at baseline should be recorded on the General Medical 
History and Baseline Conditions eCRF. 
Changes from baseline abnormalities should be recorded in participant’s notes. New or 
worsened clinically significant abnormalities should be recorded as AEs on the Adverse 
Event eCRF. 
8.2.2 
Vital Signs 
Tympanic temperature, pulse rate, respiratory rate, and blood pressure will be assessed. 
Blood pressure and pulse measurements will be assessed with a completely automated 
device. Manual techniques will be used only if an automated device is not available. 
When possible, the same arm should be used for all blood pressure measurements. The 
non-infusion arm should be used during infusion in the IV cohorts. Blood pressure and 
pulse measurements should be preceded by at least 5 minutes of rest for the participant 
in a quiet setting without distractions (e.g., television, radio, cellular phones, 
conversation). 
Vital signs (to be taken before blood collection for laboratory tests) will be measured 
after 5 minutes of rest and include temperature, SBP and DBP, pulse rate, and 
respiratory rate. Three readings of blood pressure and pulse will be taken. The first 
reading should be rejected. The second and third readings should be averaged to give 
the measurement to be recorded in the eCRF. 
8.2.3 
Electrocardiograms 
Triplicate 12-lead ECG recordings will be obtained at specified timepoints (see 
Section 1.3). Three interpretable ECG recordings (e.g., without artifacts) must be 
obtained at each specified timepoint ( 5 minutes). Single 12-lead ECG recordings may 
be obtained at unscheduled timepoints as indicated.  
All ECG recordings must be performed on a device that is equipped with reliable, 
automated algorithms for measuring heart rate and ECG intervals and capable of local 
printing. Paper copies of ECG tracings will be kept as part of the patient's permanent 
study file at the site. 
Lead placement should be as consistent as possible. ECG recordings should be 
performed after the patient has been resting in a supine or semi-supine position for at 
least 10 minutes, and the patient should remain in a supine or semi-supine position 
during recording. The same positioning should be maintained for each patient 
throughout the study. ECG recordings should be performed prior to other procedures 
scheduled at that same time (e.g., vital sign measurements, blood draws) and should not 
be performed within 2.5 hours after any meal. Circumstances that may induce changes 
in heart rate, including environmental distractions (e.g., television, radio, conversation), 
should be avoided during the pre-ECG resting period and during ECG recording. 

 
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Paper copies of all ECG tracings must be reviewed, annotated to indicate any clinical 
findings, signed, and dated by a medically qualified member of the site staff. For each 
timepoint, average heart rate, RR interval, PR interval, QRS interval, uncorrected QT 
interval, and QTcF based on machine readings of triplicate ECG tracings should be 
recorded on the appropriate eCRF. Any morphologic waveform changes or other ECG 
abnormalities must be documented on the eCRF. 
If at a particular postdose timepoint the mean QTcF is  500 ms or  60 ms longer than 
the baseline value (i.e., last value prior to initiation of study treatment), another ECG 
must be recorded, ideally within the next 5 minutes, and ECGs should be repeated at 
least hourly until two successive ECGs show resolution of the findings. A PK sample 
should be obtained if not already scheduled for that timepoint. 
8.2.4 
Clinical Safety Laboratory Assessments 
Normal ranges for the study laboratory parameters must be supplied to the Sponsor 
before the study starts. A list of clinical laboratory tests to be performed is provided in 
Appendix 4, and these assessments must be conducted in accordance with the local 
laboratories process. If analysis is required to be done centrally, the samples and assays 
should be clearly identified, and instructions may be provided by the central laboratory 
manual according to the requirements from the SoA (Section 1.3). 
The Investigator must review the laboratory report, document this review, and record any 
clinically relevant changes occurring during the study in the AE section of the eCRF. The 
laboratory reports must be filed with the source documents. Clinically significant 
abnormal laboratory findings are those which are not associated with the underlying 
disease, unless judged by the Investigator to be more severe than expected for the 
participant's condition. 
 
In the event of unexplained abnormal clinically significant laboratory test values, the 
tests should be repeated immediately and followed up until they have returned to 
the normal range and/or an adequate explanation of the abnormality is found. 
 
If such values do not return to normal/baseline within a period judged reasonable by 
the Investigator, the etiology should be identified and the Sponsor notified. 
 
If laboratory values from non-protocol-specified laboratory assessments performed 
at the local laboratory require a change in participant management or are 
considered clinically significant by the Investigator (e.g., SAE, AE, or dose 
modification), then the results must be recorded in the eCRF. 
 
Results of clinical laboratory testing will be recorded on the eCRF or received as 
electronically produced laboratory reports submitted directly from the local or central 
laboratory.  

 
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Additional blood or urine samples may be taken at the discretion of the Investigator if the 
results of any test fall outside the reference ranges or clinical symptoms necessitate 
additional testing to monitor participant safety. 
Where the clinical significance of abnormal laboratory results at screening is considered 
uncertain, screening laboratory tests may be repeated before enrollment to confirm 
eligibility. 
If there is an alternative explanation for a positive urine or blood test for drugs of abuse 
(e.g., previous occasional intake of a medication or food containing, e.g., codeine, 
benzodiazepines, or opiates), the test could be repeated to confirm washout. 
On the basis of continuous analysis of the data in this study and other studies, any 
sample type not considered to be critical for safety may be stopped at any time if the 
data from the samples collected do not produce useful information. 
8.2.5 
Medical History and Demographic Data 
Medical history includes clinically significant diseases, surgeries, reproductive status, 
smoking history, and use of alcohol and drugs of abuse, and all medications 
(e.g., prescription drugs, OTC drugs, herbal or homeopathic remedies, nutritional 
supplements) used by the participant prior to the screening visit (see Section 6.5). 
Demographic data will include age, sex, and self‑reported race/ethnicity. The information 
about race/ethnicity of CHB participants is important because host genetics may 
modulate responses to study treatments. In addition, the information can be used to infer 
the likely HBV genotype where genotype information has not been obtained in routine 
clinical care, which is a common circumstance. There are different HBV variants with 
geographical distribution (Tanwar and Dusheiko 2012; Sunbul 2014) that show different 
transmission modalities (e.g., vertical, in childhood, in adulthood), disease course, and 
response to treatment. The relevance of HBV genotypes is that HBV genotypes have a 
distinct geographical distribution and are known to influence clinical and virological 
parameters to treatment responses to, for example, IFN (Rajoriya et al. 2017). 
For the participants with CHB, the detailed HBV history will be documented, which will 
include date of HBV diagnosis, mode of HBV infection (if known), HBV genotype (if 
documented), all previous HBV treatments and outcomes of treatments, occurrence of 
NUC resistance (if any), previous evaluations of cirrhosis, and dates/outcomes of liver 
biopsies (if any). 
8.3 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
The definitions of an AE or SAE can be found in Appendix 2. AESI and disease-related 
events and/or disease-related outcomes not qualifying as AEs or SAEs are discussed in 
Section 8.3.6. 

 
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The Investigator and any qualified designees are responsible for ensuring that all AEs 
(including assessment of seriousness, severity, and causality; see Appendix 2) are 
recorded on the Adverse Event eCRF and reported to the Sponsor in accordance with 
instructions provided in this section and in Appendix 2. 
Procedures used for recording AEs are provided in Appendix 3: 
 
Diagnosis versus signs and symptoms: 
– 
Infusion-/injection-related reactions 
– 
Other AEs 
 
AEs occurring secondary to other events 
 
Persistent or recurrent AEs 
 
Abnormal laboratory values 
 
Abnormal vital sign values 
 
Abnormal liver function tests 
 
Deaths 
 
Preexisting medical conditions 
 
Lack of efficacy or worsening of the condition being studied 
 
Hospitalization or prolonged hospitalization 
 
8.3.1 
Period and Frequency for Collecting Adverse Event and 
Serious Adverse Event Information 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Appendix 2. 
Investigators will seek information on AEs at each participant’s contact. All AEs, whether 
reported by the participant or noted by study personnel, will be recorded in the 
participant’s medical record and on the Adverse Event eCRF as follows: 
After informed consent has been obtained but prior to initiation of study treatment, 
only SAEs caused by a protocol-mandated intervention should be reported (e.g., SAEs 
related to invasive procedures such as biopsies). Any other AE should not be reported. 
After initiation of study treatment, all AEs, regardless of relationship to study 
treatment, will be reported until the last scheduled follow-up visit. 
Post-study AEs and SAEs: The Investigator is not required to actively monitor 
participants for AEs after the end of the AE reporting period, defined as their last 
scheduled follow-up visit. 
However, if the Investigator learns of any SAE (including a death) or other AEs of 
concern that are believed to be related to prior treatment with study treatment at any 

 
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time after a participant has been discharged from the study, and the Investigator 
considers the event to be reasonably related to the study treatment or study 
participation, the Investigator must promptly notify the Sponsor. For the procedure of 
reporting, see Appendix 2. 
8.3.2 
Method of Detecting Adverse Events and Serious Adverse 
Events 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrence. 
A consistent methodology of non-directive questioning should be adopted for eliciting AE 
information at all participant evaluation timepoints. 
8.3.3 
Follow-Up of Adverse Events and Serious Adverse Events 
8.3.3.1 
Investigator Follow-Up 
The Investigator should follow up on each AE until the event has resolved to baseline 
grade or better, the event is assessed as stable by the Investigator, the event is 
otherwise explained, the participant is lost to follow-up (Section 7.3), or the participant 
withdraws consent. Every effort should be made to follow up on all SAEs considered to 
be related to study treatment or study-related procedures until a final outcome can be 
reported. 
During the study period, resolution of AEs (with dates) should be documented on the 
Adverse Event eCRF and in the participant’s medical record to facilitate source data 
verification. If, after follow-up, return-to-baseline status or stabilization cannot be 
established, an explanation should be recorded on the Adverse Event eCRF. 
All pregnancies reported during the study should be followed up on until pregnancy 
outcome and reported according to the instructions provided in Section 8.3.5. 
8.3.3.2 
Sponsor Follow-Up 
For SAEs, AESIs, and pregnancies, the Sponsor or a designee may follow up by 
telephone, fax, electronic mail, and/or a monitoring visit to obtain additional event details 
and outcome information (e.g., from hospital discharge summaries, consultant reports, 
and/or autopsy reports) to perform an independent medical assessment of the reported 
event. 
8.3.4 
Regulatory Reporting Requirements for Serious Adverse 
Events 
Immediate notification by the Investigator to the Sponsor of an SAE (regardless of 
relationship to study treatment) is essential so that legal obligations and ethical 
responsibilities towards the safety of participants and the safety of a study treatment 
under clinical investigation are met. 

 
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The Sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study treatment under clinical 
investigation. The Sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRB/IEC, and Investigators.  
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and Sponsor policy and 
forwarded to Investigators as necessary.  
An Investigator who receives an Investigator safety report describing an SAE or other 
specific safety information (e.g., summary or listing of SAEs) from the Sponsor will 
review and then file it along with the Investigator’s Brochure and notify the IRB/IEC, if 
appropriate according to local requirements. 
For immediate (i.e., no more than 24 hours after learning of the event) and expedited 
reporting requirements from Investigator to Sponsor and from Sponsor to Health 
Authority, Investigators, IRB and EC, see Appendix 2, Section 5. 
8.3.4.1 
Emergency Medical Contacts 
To ensure the safety of study participants, access to the Medical Monitors is available 
24 hours per day, 7 days per week. Details will be available separately. 
8.3.5 
Pregnancy 
POCBP will be instructed to immediately inform the Investigator if they become pregnant 
during the study or within 24 weeks after the final dose of study treatment, whichever is 
longer. 
Male participants will be instructed through the ICF to immediately inform the 
Investigator if their partner becomes pregnant during the study or within 24 weeks after 
the final dose of study treatment. 
If a pregnancy is reported, the Investigator should inform the Sponsor within 24 hours of 
learning of the pregnancy and follow up via the pregnancy reporting process as detailed 
in Appendix 5. All pregnancies reported during the study should be followed up until 
there is a pregnancy outcome, with follow-up information on the infant collected 
according to procedures outlined in Appendix 5. 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, and ectopic pregnancy) are considered SAEs (Appendix 5). 
8.3.6 
Adverse Events of Special Interest 
AESI are required to be reported by the Investigator to the Sponsor immediately (i.e., no 
more than 24 hours after learning of the event; see Appendix 2 for reporting 
instructions). 

 
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AESI for this study include the following: 
 
Cases of an elevated ALT or AST value in combination with either an elevated 
bilirubin value or clinical jaundice, as defined in Appendix 3. 
 
Suspected transmission of an infectious agent by the study treatment, defined as: 
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, is 
considered an infectious agent. A transmission of an infectious agent may be 
suspected from clinical symptoms or laboratory findings that indicate an 
infection in a participant exposed to a medicinal product. This term applies only 
when a contamination of the study treatment is suspected. 
 
8.3.7 
Management of Specific Adverse Events 
Injection-site reactions or hypersensitivity reactions will be managed at the Principal 
Investigator’s discretion with appropriate documentation that the treatment course was in 
reaction to evident findings (i.e., acetaminophen administered in response to 
documented fever or pain, graded use of antihistamine, glucocorticoids, or epinephrine 
for appropriately severe allergic findings, meperidine administered for documented 
rigors). If the participant experiences any suspected HBsAg-HBsAb immune complex 
mediated AEs (e.g., serum sickness; please refer to the RO7565020 IB for more 
information), an unscheduled sample will be collected (see Table 9), and the participant 
will be managed according to institutional practice at the Principal Investigator’s 
discretion. No prophylactic treatments that could mask clinical findings that may emerge 
upon dosing with study drug will be administered without prior consultation with the 
Sponsor's Medical Monitor. If a study drug-related anaphylactic or serious 
hypersensitivity reaction occurs, administration of RO7565020 should be stopped 
immediately and permanently discontinued. 
In the case of a possible event of ALT elevation or virological breakthrough during study 
treatment in Parts 2 and 3 in participants with CHB, please consider the following 
recommended guidelines for management of specific AEs (Table 9). 

 
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Table 9 
Guidelines for Managing Specific Adverse Events 
Event 
Action to Be Taken 
Injection-site reaction 
Infusion-related reaction 
Hypersensitivity reactions 
 
Manage according to institutional practice. 
 
If the severity of the event is Grade  2, collect unscheduled 
safety samples including ADA, complement activation, CRP, 
hematology, blood chemistry, and coagulation. 
Study drug-related 
anaphylactic or serious 
hypersensitivity reaction 
 
Stop administration of RO7565020 immediately and 
permanently discontinue RO7565020.  
 
Manage according to institutional practice.  
 
Collect unscheduled safety samples including ADA, 
complement activation, CRP, hematology, blood chemistry, 
and coagulation. 
For Parts 2 and 3 only (participants with CHB) 
Suspected HBsAg-
HBsAb immune complex 
mediated AEs 
(e.g., serum sickness) 
 
Manage according to institutional practice.  
 
Collect unscheduled safety samples including ADA, 
complement activation, CRP, hematology, blood chemistry, 
and coagulation. 

 
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Table 9 
Guidelines for Managing Specific Adverse Events (cont.) 
Event 
Action to Be Taken 
For Parts 2 and 3 only (participants with CHB) (cont.) 
ALT elevations during 
treatment: 
 
If ALT elevation with preserved hepatic function (e.g., no 
significant changes in bilirubin, INR, PT, albumin, and/or 
ALP):  
o 
ALT 3–10  ULN: Repeat ALT, LFTs (total bilirubin, direct 
bilirubin, AST, ALP, albumin), coagulation (INR, PT), and 
PD parameters (HBV DNA, HBsAg) every week until 
ALT  3  ULN. 
o 
ALT  10  ULN: Interrupt RO7565020 (in Part 3), and 
continue NUC treatment. Repeat ALT, LFTs, 
coagulation, and PD parameters twice weekly until ALT 
level  10  ULN, then weekly until ALT  3  ULN. 
Consider re-introducing RO7565020 on a case-by-case 
basis based on subsequent laboratory results. 
 
If ALT elevation accompanied by declining liver synthetic 
and excretory functions (total bilirubin  2  ULN, or 
albumin  3.0 g/dL, or INR  1.5) or other signs of hepatic 
impairment (severe fatigue, vomiting): 
o 
Discontinue RO7565020 (in Part 3), and continue NUC 
treatment. 
o 
Repeat ALT, LFTs, coagulation, and PD parameters 
twice weekly until levels return towards baseline levels or 
normal range. 
o 
Investigate the participant for potential etiologies of the 
laboratory changes. 
o 
If alternative reasons/diagnoses cannot explain the 
laboratory changes, potential DILI will be considered. 
Notes: 
o 
Frequency of monitoring may need to be adjusted on the 
basis of clinical scenario and severity of injury.  
o 
As the central laboratory results generation and reporting 
will take time, additional local laboratory tests may be 
performed at the same time as the central laboratory 
test, and decision-making may be based on local 
laboratory results. 
o 
For marked and/or persistent ALT elevations, collect a 
spare serum sample (to allow retrospective evaluation of 
potential etiologies) and consider liver biopsy on a case-
by-case basis (if deemed clinically relevant).  
 
If ALT elevations are associated with increased HBV DNA 
levels, virological breakthrough will be suspected and 
managed as described below.  

 
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Table 9 
Guidelines for Managing Specific Adverse Events (cont.) 
Event 
Action to Be Taken 
For Parts 2 and 3 only (participants with CHB) (cont.) 
Virological breakthrough 
 
Participants with suspected virological breakthrough (HBV 
DNA  100 IU/mL or  1 log increase from nadir) during 
treatment will attend a study visit (scheduled or 
unscheduled) within 2 weeks for: 
o 
a confirmatory testing that HBV DNA  100 IU/mL 
o 
testing of plasma drug levels of the NUC, and serum 
levels of RO7565020 
o 
collection of an additional sample for potential resistance 
testing, and 
o 
thorough evaluation of compliance and factors that may 
be affecting treatment compliance 
 
If virological breakthrough is confirmed:  
o 
The additional sample will be further tested for HBV 
genome characterization through HBV DNA and/or HBV 
RNA sequencing and where feasible phenotyping 
o 
The Investigator will manage the CHB participant’s NUC 
treatment, according to current guidelines and local 
regulations (guided by participant's treatment history, 
assessment of compliance, HBV DNA levels, and any 
available result of drug resistance testing). Blood sample 
for NUC PK will be collected to confirm the NUC 
treatment compliance 
o 
Consider whether the study treatment RO7565020 can 
be continued (for Part 3 only) 
Abbreviations: ADA = anti-drug antibody; AE = adverse event; ALP = alkaline phosphatase; 
ALT = alanine transaminase; AST = aspartate transaminase; CHB = chronic hepatitis B; 
CRP = C-reactive protein; DILI = drug-induced liver injury; DNA = deoxyribonucleic acid; 
HBsAb = hepatitis B antibody; HBsAg = hepatitis B surface antigen; HBV = hepatitis B virus; 
INR = international normalized ratio; LFT = liver function test; NUC = nucleos(t)ide analogue; 
PD = pharmacodynamic; PT = prothrombin time; RNA = ribonucleic acid; ULN = upper limit of 
normal. 
 
8.4 
TREATMENT OF OVERDOSE 
For this study, the dose of RO7565020 greater than the dose being studied will be 
considered an overdose. An overdose or incorrect administration of study treatment is 
not an AE unless it results in untoward medical effects (see Sections 5 and 5.2 of 
Appendix 2 for further details). 
The Sponsor does not recommend specific treatment for an overdose. 
Decisions regarding dose interruptions will be made by the Investigator and the Sponsor 
on the basis of the clinical evaluation of the participant. 

 
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In the event of an overdose, the Investigator should: 
1. 
Contact the Sponsor’s Medical Monitor immediately. 
2. 
Closely monitor the participant for AE/SAE and laboratory abnormalities until 
resolved. 
3. 
Document the quantity of the excess dose, as well as the duration of the overdose, 
in the eCRF. 
4. 
Obtain a blood sample for PK analysis as soon as possible. 
 
8.5 
PHARMACOKINETICS 
Mandatory blood samples to evaluate serum concentrations of RO7565020 will be 
collected as outlined in the SoAs (Section 1.3). PK samples at 5 minutes after the start 
of infusion and at the end of infusion on the day of IV administration of RO7565020 
MUST NOT be taken from the same arm as that used for study treatment administration. 
In the case of a participant being unable to provide venous access on the opposite arm 
to that used for study treatment administration, the leg may be used for PK blood 
sampling. The date and time of each sample collection will be recorded in the eCRF. 
Serum concentrations of the total and active fraction of RO7565020 will be analyzed by 
fully validated assays (RDR 1119728 and RDR 1119729, respectively). During the 
course of the study, PK sampling timepoints may be modified after agreement between 
the Sponsor and Investigator on the basis of emerging data to ensure the 
pharmacokinetics of RO7565020 can be adequately characterized. Additional 
unscheduled PK samples will be taken at the time of treatment discontinuation if an 
infusion-related AE is reported (such as an infusion- or injection-related reaction [IRR]), 
SAE or an severe AE or a suspected virological breakthrough is reported (Section 8.3.7) 
or if an AE leading to dose interruption or delay of RO7565020 administration 
(Section 6.6.1) or an accidental overdose is reported (Section 8.4). 
 
Blood samples from participants treated with placebo may not be analyzed in the 
first instance but retained for subsequent analysis if appropriate. 
 
Any volume of blood samples remaining after the specified analyses may also be 
used for additional compound-related assay development and/or validation 
experiments or analyses. 
 
The PK blood samples will be destroyed no later than 2 years after the date of the 
publication of the final clinical study report (CSR). For participants who consent to RBR, 
leftover samples will be transferred to RBR (see Section 8.9). 
Drug concentration information that may unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded. 
Any changes in the timing or addition of timepoints for any planned study assessments 
must be documented and approved by the relevant study team member and archived in 
the Sponsor’s and site study files. This will not constitute a protocol amendment. The 

 
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IRB/IEC will be informed of any safety issues that require alteration of the safety 
monitoring scheme or amendment of the ICF. 
8.6 
IMMUNOGENICITY ASSESSMENTS 
As RO7565020 is a human IgG1 antibody (anti-HBs neutralizing antibody Bc1.187), 
there is a risk that ADAs against RO7565020 could develop, potentially impacting on the 
pharmacokinetics of RO7565020, reducing its efficacy, and/or potentially resulting in 
safety events, such as symptomatic hypersensitivity reaction, including immune-complex 
reactions. 
Antibodies to RO7565020 will be evaluated in serum samples collected from all 
participants according to the SoA (Section 1.3). After completing the scheduled visits, an 
additional ADA and PK sample collection may be needed, depending on the emerging 
ADA data. 
Validated screening, confirmatory, and titer assays will be employed to detect ADAs 
against RO7565020 (RDR 1119730). The date and time of each sample will be recorded 
in the eCRF. All samples collected for detection of ADA to RO7565020 will also be 
evaluated for RO7565020 serum concentration to enable interpretation of the 
immunogenicity data. 
If required, remaining volumes of ADA samples may also be used for assay 
development/validation experiments, for ADA characterization, for compound-related 
exploratory analyses, or to help develop further blood tests, after they are used for the 
mentioned intended uses. 
The serum samples will be destroyed no later than 2 years after the date of final CSR or 
after approval by the study management team or earlier depending on local regulations. 
For participants who consent to RBR, leftover samples will be transferred to RBR (see 
Section 8.9). 
Details on sampling procedures, sample storage, and shipment are documented in the 
sample documentation. 
8.7 
PHARMACODYNAMICS AND BIOMARKERS ANALYSES 
8.7.1 
HBV Biomarker Assessments 
The following well-established HBV laboratory tests will be measured using plasma or 
serum samples, as appropriate: quantitative and qualitative HBsAg, quantitative anti-
HBs, qualitative HBeAg, qualitative anti-HBe, and quantitative HBV DNA. 
Additional HBV dynamic biomarkers may be measured in all or some participants, as 
appropriate. This may include but not be limited to semi-quantitative HBeAg (calculated 
from the qualitative assay), quantitative HBV RNA, quantitative HBcrAg, quantitative 

 
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total anti-HBc, total HBsAg (post-dissociation of HBsAg:HBsAb complexes), and the 
HBsAg isoforms using plasma or serum samples. 
8.7.2 
HBV Genotype 
In addition to gathering the HBV genotype through the collection of the medical history 
from the participants with CHB, the HBV genotype will be determined through HBV RNA 
sequencing. HBV RNA will be extracted and amplified using the plasma sample 
collected on Day 1. If this sample is not collected at that visit, it can be collected at any 
other scheduled visit. If the amplification yields enough HBV RNA material, RNA-based 
sequencing will be attempted to determine the HBV genotype. The HBV genotype may 
also be inferred using alternative approaches, such as serovariant determination. 
8.7.3 
Viral Resistance Monitoring 
In some participants, HBV genome (DNA and/or RNA) sequencing may be done as 
appropriate to identify emerging mutations that may be leading to drug resistance. In the 
event of a confirmed HBV DNA breakthrough, as defined in Section 8.3.7, HBV DNA will 
be extracted and amplified using the plasma sample collected for the confirmatory HBV 
DNA quantification. If the amplification yields enough HBV DNA material, DNA 
sequencing of either the whole HBV genome or selected regions of interest will be 
attempted to determine genotype and mutations with potential to be associated with drug 
resistance and, where feasible, phenotyping. If this process fails, extraction, 
amplification, and sequencing may be attempted at a later timepoint. 
Moreover, changes in the distribution of free and total HBsAg in relation with 
RO7565020 PK and changes in the affinity of RO7565020 to potential escape mutants in 
the S gene that might have been selected for by therapy with RO7565020 may be 
measured using baseline, end of follow-up, and/or intermediary timepoint samples. 
Further characterization of such emerging mutations may be attempted through HBV 
RNA sequencing, if feasible. 
8.7.4 
Exploratory Immunology Biomarkers 
Biomarkers of systemic inflammation and immune activation will comprise assays to 
quantify cytokine/chemokine panels in blood (such as IFN-, TNF-, IL-6, and IL-8), as 
well as complement activation markers (such as C3a and SC5b-9). 
Immune phenotype, B and T cells activation status (by flow cytometry), transcriptional 
profile and inflammatory signature (scRNAseq) may be assessed in blood from 
participants with CHB. 
Ex vivo HBV-specific cellular immune responses in CHB participants may be measured 
in samples collected at sites with appropriate capability to perform the PBMC isolation 
procedure. These cells may be used to evaluate ex vivo HBV-specific cellular immune 
response by standard immune assays. These analyses will be considered as an 

 
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exploratory optional objective due to the logistic and technical challenges that might be 
experienced with obtaining viable PBMC during the conduct of a multi-center trial. 
8.7.5 
Genetic and Genomic Analyses 
8.7.5.1 
Clinical Genotyping 
A whole blood sample for germline DNA analysis will be taken once, at baseline or 
before study treatment administration. If this sample is missed, it can be collected at any 
other scheduled visit. DNA may be used to determine alleles at genes coding for human 
leukocyte antigens (i.e., HLA gene family). This information would be used for adapting 
the methodology of subsequent HBV-specific immune cell evaluations. 
To identify these variants and polymorphisms, genome-wide methods may be used. 
Given the complexity and exploratory nature of genome-wide analyses, neither 
genomics data nor analyses will be shared with Investigators or study participants unless 
required by law. Participants will not be identified by name or any other personally 
identifying information. Data arising from all biosamples, including samples for analyses 
of inherited human DNA, will be subject to the confidentiality standards described in the 
sample documentation and in Appendix 1, Section 1.4. 
8.7.5.2 
Transcriptome Analysis 
RNA extraction and subsequent gene expression profiling may be performed from 
leftover samples to identify biomarker signatures predictive or associated with treatment 
response/safety. These assessments may be performed in some of the participants if 
safety or activity rationales develop, pending approval from country health authorities 
and local ethic committees as appropriate. 
Given the complexity and nature of these analyses, genetic and genomic data and 
analyses will not be shared with Investigators or study participants unless required by 
law. Participants will not be identified by name or any other personally identifying 
information. Data arising from all biosamples including samples for analyses of inherited 
DNA will be subject to the confidentiality standards described in Appendix 1, Section 1.4. 
8.8 
PHARMACODYNAMICS AND BIOMARKER SAMPLES 
The samples may also be used for research purposes to identify biomarkers useful for 
predicting and monitoring response to RO7565020, identifying biomarkers useful for 
predicting and monitoring RO7565020 safety, assessing PD effects of RO7565020, and 
investigating mechanism of therapy resistance. Additional markers may be measured if a 
strong scientific rationale develops. 
Samples should be collected as specified in the SoA (Section 1.3). 
On the basis of continuous analysis of the data in this study and other studies, any 
sample type and/or analysis not considered to be critical for safety may be stopped at 

 
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any time if the data from the samples collected does not produce useful information or 
may be tested only in some of the participants and/or some of the scheduled visits.  
Unless otherwise specified below, all samples will be destroyed no later than 5 years 
after the date of final CSR. For participants who consent to RBR in countries where this 
applies, leftover samples will be transferred to RBR (Section 8.9). 
Any remaining samples after the specified analyses may also be used for additional 
exploratory biomarker profiling or/and (assay) validation experiments. Samples may be 
used for research to develop methods, assays, prognostics, and/or companion 
diagnostics related to HBV. 
Details on processes for collection and shipment of these samples can be found in 
separate sample documentation. 
8.8.1 
Mandatory Samples 
The following samples for PD and biomarker research are required and will be collected 
from all participants: 
8.8.1.1 
Blood Sampling 
Samples will be collected for the measurement of the HBV dynamic markers, the HBV 
genotype, the viral resistance monitoring, and the exploratory immunology biomarkers 
(see Sections 8.7.1, 8.7.2, 8.7.3,and 8.7.4) according to the SoA (Section 1.3). 
A mandatory whole blood sample will also be taken for germline DNA extraction and 
clinical genotyping of the human leukocyte antigen gene family from every participant. If 
the sample is missed on Day 1, it can be collected at any other scheduled visit. The 
whole blood sample for clinical genotyping and derived analytical material will be 
destroyed immediately after the publication of the associated report. 
8.8.1.2 
Urine Sampling 
Urine samples will be collected according to the SoA (Section 1.3) for safety 
assessment. 
8.9 
SAMPLES FOR RESEARCH BIOSAMPLE REPOSITORY 
8.9.1 
Overview of the Research Biosample Repository 
The Roche RBR is a centrally administered group of facilities for the long-term storage of 
human biologic samples, including body fluids, solid tissues, and derivatives thereof 
(e.g., DNA, RNA, proteins, peptides). The collection, storage, and analysis of the RBR 
samples will facilitate the rationale design of new pharmaceutical agents and the 
development of diagnostic tests, which may allow for individualized drug therapy for 
patients in the future. 

 
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Samples for the RBR will be collected from participants who give specific consent to 
participate in this optional RBR in countries where this applies. Samples collected for 
RBR can be used (but are not thus limited) to achieve the following objectives: 
 
To study the association of biomarkers with efficacy or progressive disease. 
 
To identify safety biomarkers that are associated with susceptibility to developing 
AEs or can lead to improved AE monitoring or investigation. 
 
To increase knowledge and understanding of disease biology and drug safety. 
 
To study treatment response, including drug effects and the processes of drug 
absorption and disposition.  
 
To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays. 
 
8.9.2 
Sample Collection 
For Parts 2 and 3, leftover plasma, serum, blood, and urine samples (including 
derivatives of these, such as DNA or RNA extracts or PBMCs prepared from blood) will 
be stored in the RBR and used for research purposes, including, but not limited to, 
research on biomarkers related to RO7565020, diseases, or drug safety. Additional 
whole blood samples for RBR will be collected from RBR-consenting participants 
according to SoA table (Section 1.3). 
Participants will not be identified by name or any other personally identifying information. 
Data generated from RBR samples will be analyzed in the context of this study but may 
also be explored in aggregate with data from other studies. The availability of a larger 
dataset will assist in identification and characterization of important biomarkers and 
pathways to support future drug development. 
For all samples, dates of consent and sample collection should be recorded on the 
associated RBR page of the eCRF. Details on processes for collection and shipment of 
these samples can be found in separate sample documentation. 
RBR samples will be stored and used until they are exhausted or no longer needed. The 
RBR storage period will be in accordance with the IRB/EC‑approved ICF and applicable 
laws (e.g., Health Authority requirements). 
The repository samples will be subject to the confidentiality standards (as described 
under “Confidentiality” in Appendix 1). 
8.10 
HEALTH ECONOMICS OR MEDICAL RESOURCE UTILIZATION 
AND HEALTH ECONOMICS 
Health economic/medical resource utilization and health economic parameters are not 
evaluated in this study. 

 
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8.11 
TIMING OF STUDY ASSESSMENTS 
8.11.1 
Screening and Pre-treatment Assessments 
Written informed consent for participation in the study must be obtained before 
performing any study-specific screening tests or evaluations. ICFs for enrolled 
participants and for participants who are not subsequently enrolled will be maintained at 
the study site. 
All screening and all pre-treatment assessments (related to entry criteria) must be 
completed and reviewed by the Investigator to confirm that participants meet all eligibility 
criteria. The Investigator will maintain a screening log to record details of all participants 
screened and to confirm eligibility or record reasons for screening failure. 
An Eligibility Screening Form documenting the Investigator’s assessment of each 
screened participant with regard to the protocol’s inclusion and exclusion criteria is to be 
completed by the Investigator and kept at the investigational site. 
In Part 1a and Part 1b, screening and pre-treatment assessments will be performed 
within 28 days prior to Day 1, unless otherwise specified. In Parts 2 and 3, screening 
and pre-treatment assessments will be performed within 56 days prior to Day 1, unless 
otherwise specified.  
8.11.2 
Assessments during Treatment 
Under no circumstances will participants who enroll in this study and have completed 
treatment as specified be permitted to be allocated a new randomization number and 
re-enroll in the study. 
All assessments must be performed as per the SoA (Section 1.3). Assessments 
scheduled on the day of study treatment administration should be performed prior to 
administration of study treatment, unless otherwise noted in the SoAs. 
Exceptional measures during the COVID-19 pandemic, such as adjustments in study 
visits, may be considered (see Section 8.11.6) 
8.11.3 
Assessments at Study Completion/Early Termination Visit 
Participants who prematurely discontinue study treatment but remain in the study should 
continue to attend the follow-up visits. All follow-up assessments must be performed as 
per SoA (Section 1.3). 
8.11.4 
Follow-Up Assessments 
Follow-up assessments must be performed as per SoA (Section 1.3). After the study 
completion/early termination visit, AEs should be followed as outlined in Sections 8.3.1 
and 8.3.3. 

 
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8.11.5 
Assessments at Unscheduled Visits 
If clinically indicated, any assessment or sample specified in the SoAs (Section 1.3) can 
be performed any time as unscheduled assessment or sample at the discretion of the 
Investigator. Unscheduled eCRFs will be used to record any assessments performed 
during an unscheduled visit. 
For unscheduled sample collection related to specific safety events, please see 
Section 8.3.7. For unscheduled PK sample collection, please see Section 8.2.3 and 
Section 8.5. 
8.11.6 
Exceptional Measures during COVID-19 Pandemic 
If COVID-19 pandemic related special restriction happens, exceptional measures, such 
as adjustments in study visits, may be considered if in the overall best interest of the 
participant. Adjustments may include: 
 
Use of alternative facility for assessments (e.g., local laboratory or imaging centers). 
 
Replacement of a study visit with alternative methods for assessments (such as 
phone contacts or virtual visits to assess safety). 
 
Postponement of a study visit or of individual assessments. 
 
Temporary suspension of sample collection. 
 
A robust benefit–risk assessment should be performed by the Investigator and 
discussed with the Medical Monitor. This assessment will be fully documented, and any 
deviations to the protocol will be recorded in accordance with the Sponsor standard 
procedure. 

 
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9. 
STATISTICAL CONSIDERATIONS 
9.1 
STATISTICAL HYPOTHESES 
No statistical hypothesis testing is planned for this study. 
9.2 
SAMPLE SIZE DETERMINATION 
The sample size was determined by practical considerations and not based on statistical 
power calculations. 
Approximately 48 to 56 healthy participants and 30 to 54 participants with CHB 
(depending on whether the optional cohorts are conducted) are planned to be enrolled in 
this study.  
In Part 1a, 8 participants with 6:2 ratio (active treatment versus placebo) are planned to 
be enrolled into each cohort. Six cohorts are planned. Additional cohort(s) with 
intermediate dose level(s) is/are allowed. 
In Part 1b, 8 participants with 6:2 ratio (active treatment versus placebo) are planned to 
be enrolled if considered to be necessary based on the data of Part 1a.  
In Part 2a and 2b, 6 CHB participants (all active treatment) per dose cohort are planned 
to be enrolled. Seven cohorts are planned including 2 optional cohorts.  
In the optional Part 3, 6 CHB participants (active treatment) in each cohort ( 2 cohorts) 
are planned to be enrolled if considered necessary based on the data of Parts 1 and 2. 
Dose escalation decisions will be made based on data from 5 or 6 participants from each 
cohort. With 5 participants per dose cohort, there is an at least 80% chance to observe 
at least one AE that has an incidence rate of 28% in the population; with 6 participants 
per dose cohort, there is an at least 80% chance to observe at least one AE that has an 
incidence rate of 24% in the population. 
Participants who discontinue study prematurely or withdraw consent from the study for 
non-safety reason may be replaced in order to obtain the required participant numbers 
for a dose decision. Additional participants may be enrolled in additional dose cohorts 
that assess lower or repeat doses. In Parts 2 and 3, except for the replacements, 
additional participants may be enrolled in some cohorts in case the variability in PK and 
PD is too high in participants with CHB. 

 
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9.3 
ANALYSIS SETS 
For purposes of analysis, the following populations are defined in Table 10. 
Table 10 Analysis Sets 
Participant Analysis Set 
Description 
PD 
The analyses of the viral dynamic response will include all 
participants with CHB who received at least one dose of study 
treatment (RO7565020 or placebo). Participants will be analyzed 
according to the treatment group to which they were 
randomized/assigned. 
Safety 
All participants randomized/assigned to study treatment and who 
received at least one dose of the study treatment, whether 
prematurely withdrawn from the study or not, will be included in 
the safety analysis.  
PK 
All participants who have received at least one dose of study 
treatment and who have data from at least one postdose sample 
will be included in the PK analysis set. Participants will be 
excluded from the PK analysis set if they significantly violate the 
inclusion or exclusion criteria, deviate significantly from the 
protocol, or if data are unavailable or incomplete which may 
influence the PK analysis. Excluded cases will be documented 
with the reason for exclusion. All decisions on exclusions from the 
analysis will be made prior to database closure. 
Immunogenicity 
Participants who had at least one ADA assessment will be 
included and analyzed according to the treatment they actually 
received. The relationship between ADA status and safety, 
efficacy, PK, and biomarker endpoints will be analyzed and 
reported descriptively via subgroup analyses. 
Abbreviations: ADA = anti-drug antibody; PK = pharmacokinetics; PD = pharmacodynamics. 
 
9.4 
STATISTICAL ANALYSES 
Statistical summaries will be descriptive in nature and will be reported separately for 
each part of the study within the CSR. All study participants who are randomized to 
receive placebo within one part will be pooled as respective placebo control groups for 
each part. 
9.4.1 
Demographics and Baseline Characteristics 
Descriptive statistics will be used for demographic and baseline disease characteristics 
as applicable for each part of the study. These will include age, gender, race, ethnicity, 
country of origin, weight, height, BMI, HBV baseline characteristics (e.g., HBsAg levels), 
HBV history (e.g., duration of HBV diagnosis, HBV treatment history, and liver fibrosis 
status), and, where measurable (participants with detectable HBV RNA), the viral 
genotype. For Part 1a and Part 1b, all participants who are randomized to receive SC or 
IV placebo will be pooled as respective SC or IV placebo control groups, according to 
each part of the study. 

 
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For continuous variables, mean, standard deviation, median, and minimum and 
maximum values will be presented. For categorical data, the proportion of study subjects 
in each category will be summarized. 
9.4.2 
Safety Analyses 
All safety analyses will be based on the safety analysis set (see Table 11). Participants 
will be summarized by cohort. In addition, all study participants who are randomized to 
receive SC or IV placebo will be pooled as respective SC or IV placebo control groups, 
according to each part of the study.  
The safety data, including AEs, injection-site reactions, reasons for withdrawal from 
study, laboratory data, ECG, concomitant medications, vital signs, and physical 
examination results will be listed and summarized descriptively. Marked abnormalities of 
laboratory data will be flagged. As appropriate, listings, summary tables and graphs 
(participant plot and/or mean plots) will be provided to describe safety and tolerability 
assessments. 
Table 11 Safety Statistical Analysis Methods 
Endpoint 
Statistical Analysis Methods 
Adverse events 
The original terms recorded on the eCRF by the Investigator for AEs will be 
coded by the Sponsor. 
AEs will be summarized by mapped term and appropriate thesaurus level. 
Frequency and severity of adverse events will be summarized. 
Clinical laboratory 
tests 
All clinical laboratory data will be stored on the database in the units in 
which they were reported. Laboratory test values will be presented in 
International System of Units (SI units) by individual outputs with flagging of 
abnormal results. 
Summary tables of absolute value and change from baseline over time will 
be displayed. Shifts in DAIDS grades v2.1 from baseline to the worst grade 
observed during treatment will be presented for selected laboratory 
parameters. For details on standard reference ranges and data 
transformation and the definition of laboratory abnormalities, see 
Appendix 4. 
Vital signs 
Vital sign data will be presented with flagging of values outside the normal 
ranges and flagging of abnormalities. 
Mean changes from baseline and absolute value over time will be provided. 
ECG data analysis ECG data will be presented using appropriate outputs, as detailed in 
Section 9.4.2.1. 
Concomitant 
medications 
The original terms recorded on the participants’ eCRF by the Investigator 
for concomitant medications will be standardized by the Sponsor by utilizing 
a mapped term and appropriate drug dictionary level. 
Concomitant medications will be presented using appropriate outputs. 
Abbreviations: AE = adverse events; DAIDS = Division of AIDS; ECG = electrocardiogram; 
eCRF = electronic case report form; SI = Système International d’Unités. 
 

 
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9.4.2.1 
ECG Data Analysis 
ECG data will be presented by individual listings with flagging of values outside the 
normal ranges and flagging of marked abnormalities. Summary descriptive statistics for 
the actual values and changes from baseline will be tabulated by nominal time for HR, 
QRS duration, PR and QTcF. For multiple measurements taken at a nominal timepoint, 
the average of these measurements will be used as the value at that nominal timepoint 
in all summaries. In addition, QTcF will be categorized at each timepoint as 450 ms, 
450 to 480 ms, 480 to 500 ms and 500 ms and summarized. Similarly, a summary 
will be provided of the QTcF changes from baseline at each timepoint categorized as 
30 ms, 30 to 60 ms, and 60 ms. Changes of the overall ECG interpretation and 
T-wave and U-wave morphology will be summarized. 
9.4.3 
Pharmacokinetic Analyses 
Analyses will be carried out on the PK analysis set. All PK parameters will be presented 
by listings and descriptive summary statistics (arithmetic means, geometric means, 
medians, ranges, standard deviations, and coefficients of variation) separately by group 
or cohorts. 
Individual and mean serum total and active RO7565020 concentration versus time data 
will be tabulated and plotted on linear or semi-logarithmic scales by dose level, and/or by 
route of administration in different parts.  
PK parameters will be read directly from the serum total and active concentration-time 
profiles, or calculated using standard non-compartmental methods. The following PK 
parameters will be computed for RO7565020 as appropriate. 
 
Time to maximum concentration (tmax) 
 
Maximum serum concentration observed (Cmax) 
 
AUC from 0 to last sampling point or last quantifiable sample, whichever comes first 
(AUClast) 
 
AUC from 0 to infinity (AUCinf) 
 
Terminal half-life (t1/2) 
 
Volume of distribution (Vss) and clearance (CL) (IV only) 
 
Apparent clearance (CL/F) and apparent volume of distribution (Vz/F) (SC only) 
 
Further data analysis to estimate the dose-exposure relationships and the potential 
impact of TMDD and of ADAs on PK of RO7565020 will be also conducted as 
appropriate. 
Calculations of additional PK parameters and population pharmacokinetic (popPK) 
analysis at the end of the dose escalation will be performed as data allow it. Population 
and individual PK parameters will be estimated, and the influence of various covariates 

 
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(such as age, sex, body weight and baseline HBsAg levels [only in Parts 2 and 3]) on 
these parameters will be investigated in an exploratory way. 
The details of the popPK and any other exploratory data analyses will be reported in 
documents separate from the CSR. 
9.4.4 
Immunogenicity Analyses 
The immunogenicity analyses will include all participants with at least one ADA 
assessment, irrespective of whether or not the participant receives any 
treatment (Shankar et al. 2014). 
The numbers and proportions of ADA-positive participants and ADA-negative 
participants at baseline (baseline prevalence) and after study treatment administration 
(post-baseline incidence during both the treatment and follow-up periods) will be 
summarized. 
 
Participants are considered to be ADA positive if they are ADA negative or have 
missing data at baseline but develop an ADA response following study treatment 
administration (treatment-induced ADA response), or if they are ADA positive at 
baseline and the titer of one or more post-baseline samples is at least 4-fold 
(e.g., 0.60-titer units) greater than the titer of the baseline sample (treatment-
enhanced ADA response).  
 
Treatment-induced ADA responses will be further categorized as either: 
– 
Transient ADA response: defined as a) ADA negative or no ADA available at 
baseline, and b) at least one post-treatment ADA-positive sample, and c) only 
one ADA-positive sample or the time between the first and last ADA-positive 
sample is less than 16 weeks and d) the last ADA sample is negative 
– 
Persistent ADA response: defined as a) ADA negative or missing data at 
baseline, and b) post-treatment ADA-positive samples over 16 weeks or more 
or the last ADA timepoint is positive (Shankar et al. 2014) 
 
Participants are considered to be ADA negative if they are ADA negative; if they 
have missing data at baseline and all post-baseline samples are negative; or if they 
are ADA positive at baseline but do not have any post-baseline samples with a titer 
that is at least 4 fold greater than the titer of the baseline sample (treatment 
unaffected). 
 
The relationship between ADA status and safety, efficacy, PK, and biomarker endpoints 
will be analyzed and reported descriptively via subgroup analyses. 
9.4.5 
Pharmacodynamic Analyses 
Viral dynamic response analysis will be done for the participants with CHB enrolled in 
Part 2a, Part 2b, and Part 3, and will be based on the PD analysis set (see Table 10). 
Descriptive statistics will be utilized to summarize the viral dynamic response outcome 

 
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measure of serum HBsAg and HBeAg (Table 12), and the exploratory viral dynamic 
endpoints of HBV RNA, HBcrAg, total HBsAg, HBsAg isoform (Table 13). 
Table 12 Viral Dynamic Response Statistical Analysis Methods 
Endpoint 
Statistical Analysis Methods 
HBsAg change from baseline 
Time course profile: summary descriptive statistics by cohort 
(including mean, standard deviation, median, minimum, and 
maximum) (in log10 IU/mL and % change from baseline) at 
each timepoint. 
Maximum reduction of HBsAg 
Summary descriptive statistics by cohort (including mean, 
standard deviation, median, minimum, and maximum) 
(in log10 IU/mL and % reduction). 
HBsAg loss and HBsAg 
seroconversion 
Proportion of HBsAg loss and HBsAg seroconversion at each 
timepoint. Percentages are based on PD analysis set.  
HBeAg loss and HBeAg 
seroconversion 
Proportion of HBeAg loss and HBeAg seroconversion at each 
timepoint. Percentages are based on PD analysis set. 
Abbreviations: HBeAg = hepatitis B e antigen; HBsAg = hepatitis B surface antigen; 
PD = pharmacodynamic. 
 
Table 13 Exploratory Viral Dynamic Response Statistical Analysis 
Methods 
Endpoint 
Statistical Analysis Methods 
Baseline and change from 
baseline of HBV RNA, 
HBcrAg, and total HBsAg 
Time course profile: summary descriptive statistics by cohort 
(including mean, standard deviation, median, minimum, and 
maximum) (in log10 IU/mL) at each timepoint. 
Abbreviations: HBcrAg = hepatitis B core-related antigen; HBsAg = hepatitis B surface antigen; 
HBV = hepatitis B virus. 
 
9.4.6 
Pharmacokinetic/ Pharmacodynamic Relationships 
In order to inform the design and selection of dose regimens in further clinical trials, 
exploratory analysis between PK and/or PD, antiviral response and/or safety by 
modeling and simulation (e.g., using nonlinear mixed effects modeling and/or 
physiologically-based pharmacokinetic [PBPK] analysis) based on study data may be 
applied if considered appropriate.  
The details of PK/PD modeling results will be reported in documents separate from the 
CSR. 
9.4.7 
Other Analyses 
Data from exploratory biomarkers will be listed, and descriptive statistics, by cohorts and 
between participants with CHB and healthy participants (when available), at each 

 
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timepoint, will be applied in relation to viral and immune markers and potentially PK 
parameters. Graphic displays may be used as appropriate. 
This exploratory study will have ongoing safety assessment and safety data reviews for 
the purpose of dose escalation/decisions that do not qualify as formal interim analyses 
(IAs). Given the hypothesis-generating nature of this study, the Sponsor may choose to 
conduct interim analyses. The decision to conduct an optional IA and the timing of the 
analysis will be documented in the Sponsor’s electronic trial master file (eTMF) prior to 
the conduct of the IA. The IA will be performed and interpreted by Sponsor’s study team 
personnel, who will have full access to trial data. Access to treatment assignment 
information will follow the Sponsor’s standard procedure. 
9.5 
SUMMARIES OF CONDUCT OF STUDY 
All protocol deviations will be listed. Data for study drug administration and concomitant 
medication will be listed. The number of participants who were randomized or who 
discontinued and completed the study will be summarized and listed. 

 
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10. 
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11. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
The following section includes standard appendices such as Appendix 1 (For regulatory, 
ethical and study oversight considerations), Appendix 2 (For AE definitions, reporting) 
and Appendix 3 (Procedures of recording AEs), Appendix 4 (Clinical laboratory tests), 
Appendix 5 (Contraceptive guidance and collection of pregnancy information), 
Appendix 6 (Investigational medicinal product and auxiliary medicinal product 
designations), and Appendix 7 (List of abbreviations). 
 

 
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Appendix 1  
Regulatory, Ethical, and Study Oversight Considerations 
1. 
REGULATORY AND ETHICAL CONSIDERATIONS 
1.1. 
COMPLIANCE WITH LAWS AND REGULATIONS 
This study will be conducted in full conformance with the ICH E6 guideline for Good 
Clinical Practice (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 individual. The study will comply with the requirements of the 
International Council for Harmonisation (ICH) E2A guideline (Clinical Safety Data 
Management: Definitions and Standards for Expedited Reporting). Studies conducted in 
the United States or under a U.S. Investigational New Drug (IND) application will comply 
with U.S. Food and Drug Administration (FDA) regulations and applicable local, state, 
and federal laws. Studies conducted in the E.U./EEA will comply with the E.U. Clinical 
Trial Directive (2001/20/EC) or Clinical Trials Regulation (536/2014) (EEA sites only), 
and all other applicable local regulations. 
1.2. 
INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE 
This protocol, the Master Informed Consent Forms (ICFs), any information to be given to 
the participant (e.g. advertisements, diaries etc.), and relevant supporting information 
must be submitted to the Institutional Review Board (IRB)/ethics committee (EC) by the 
Principal Investigator or the Sponsor, as required by local laws and regulations and 
reviewed and approved by the IRB/EC before the study is initiated. In addition, any 
participant recruitment materials must be approved by the IRB/EC. 
The Principal Investigator or the Sponsor, as required by local laws and regulations, is 
responsible for providing written summaries of the status of the study to the IRB/EC 
annually or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/EC. Investigators are also responsible for promptly 
informing the IRB/EC of any protocol amendments (Section 2.3.1 of this appendix). 
The Investigator should follow the requirements for reporting all adverse events (AEs) to 
the Sponsor. Investigators may receive written IND 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/EC, and archived in the site’s 
study file. 
1.3. 
INFORMED CONSENT 
The Sponsor’s Master ICF (and ancillary sample ICFs such as a Child’s Assent or 
Caregiver's ICF, if applicable) will be provided to each site. If applicable, it will be 
provided in a certified translation of the local language. Participants must be informed 
that their participation is voluntary. Participants will be required to sign a statement of 

 
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informed consent that meets the requirements of 21 Code of Federal Regulations (CFR) 
Part 50, local regulations, ICH guidelines, Health Insurance Portability and Accountability 
Act of 1996 (HIPAA) requirements, where applicable, and the IRB/IEC or study center. 
The Sponsor or its designee must review and approve any proposed deviations from the 
Sponsor's sample ICFs or any alternate consent forms proposed by the site (collectively, 
the “Consent Forms”) before IRB/EC submission. The final IRB/EC‑approved consent 
forms must be provided to the Sponsor for Health Authority submission purposes 
according to local requirements. Participants must be re-consented to the most current 
version of the ICF(s) during their participation in the study. A copy of the ICF(s) signed 
by all parties must be provided to the participant. 
The ICFs must be signed and dated by the participant before his or her participation in 
the study. The case history or clinical records for each participant shall document the 
informed consent process and that written informed consent was obtained prior to 
participation in the study. 
The ICFs should be revised whenever there are changes to study procedures or when 
new information becomes available that may affect the willingness of the participant to 
take part. The final revised IRB/EC-approved ICFs must be provided to the Sponsor for 
Health Authority submission purposes if required as per local regulations. 
If the ICFs are revised (through an amendment or an addendum) while a participant is 
participating in the study, the participant may be re-consented by signing the most 
current version of the ICFs or the addendum, in accordance with applicable laws and 
IRB/EC policy. For any updated or revised ICFs, the case history or clinical records for 
each participant shall document the informed consent process and that written informed 
consent was obtained using the updated/revised ICFs for continued participation in the 
study. The study team will provide guidance for which participants need to re-consent in 
the event of an update to the ICF. 
A copy of each signed ICF must be provided to the participant. All signed and dated 
ICFs must remain in each participant’s study file or in the site file and must be available 
for verification by study monitors at any time. 
Participants who are re-screened are required to sign a new ICF. 
Consent to Participate in the Research Biosample Repository 
The ICF will contain a separate section that addresses participation in the Research 
Biosample Repository (RBR). The Investigator or authorized designee will explain to 
each participant the objectives, methods, and potential hazards of participation in the 
RBR. Participants will be told that they are free to refuse to participate and may withdraw 
their samples at any time and for any reason during the storage period. A separate, 
specific signature will be required to document a participant’s agreement to provide 

 
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optional RBR samples. Participants who decline to participate will not provide a separate 
signature. 
The Investigator should document whether or not the participant has given consent to 
participate by completing the RBR Sample Informed Consent electronic case report form 
(eCRF). 
In the event of death or loss of competence of a participant who is participating in the 
research, the participant's samples and data will continue to be used as part of the RBR. 
For sites in the United States, each ICF may also include participant authorization to 
allow use and disclosure of personal health information in compliance with the U.S. 
HIPAA. If the site utilizes a separate Authorization Form for participant authorization for 
use and disclosure of personal health information under the HIPAA regulations, the 
review, approval, and other processes outlined above apply, except that IRB review and 
approval may not be required per study site policies. 
Approval by the Institutional Review Board or Ethics Committee 
Collection, storage, and analysis of RBR samples is contingent upon the review and 
approval of the exploratory research and the RBR portion of the ICF by each site's 
IRB/EC and, if applicable, an appropriate regulatory body. If a site has not been granted 
approval for RBR sampling, this section of the protocol will not be applicable at that site. 
Withdrawal from the Research Biosample Repository 
Participants who give consent to provide samples for the RBR have the right to withdraw 
their samples at any time for any reason. If a participant wishes to withdraw consent to 
the testing of his or her samples, the Investigator must inform the Medical Monitor and 
Site Monitor in writing of the participant’s wishes using the RBR Withdrawal Form and, if 
the study is ongoing, must enter the date of withdrawal on the RBR Withdrawal of 
Informed Consent eCRF. The participant will be provided with instructions on how to 
withdraw consent after the study is closed. A participant's withdrawal from Study 
BP44118 does not, by itself, constitute withdrawal of samples from the RBR. Likewise, a 
participant’s withdrawal from the RBR does not constitute withdrawal from Study 
BP44118. Data already generated before time of withdrawal of consent to RBR will still 
be used. 
1.4. 
CONFIDENTIALITY 
Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect such 
data against accidental or unlawful loss, alteration, or unauthorized disclosure or access.  
In the event of a data security breach, appropriate mitigation measures will be 
implemented. 

 
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Participants will be assigned a unique identifier by the Sponsor. Any participant records 
or datasets that are transferred to the Sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred.  
The participant must be informed that his/her personal study-related data will be used by 
the Sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the participant. 
Medical information may be given to a participant’s personal physician or other 
appropriate medical personnel responsible for the participant’s welfare, for treatment 
purposes. 
The participant must be informed that his/her medical records may be examined by 
Clinical Quality Assurance auditors or other authorized personnel appointed by the 
Sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory 
authorities. 
Study data may be submitted to government or other health research databases or 
shared with researchers, government agencies, companies, or other groups that are not 
participating in this study. These data may be combined with or linked to other data and 
used for research purposes, to advance science and public health, or for analysis, 
development, and commercialization of products to treat and diagnose disease. In 
addition, redacted clinical study reports and other summary reports will be provided upon 
request. 
Confidentiality for Research Biosample Repository 
Data generated from RBR samples must be available for inspection upon request by 
representatives of national and local Health Authorities, and Roche monitors, 
representatives, and collaborators, as appropriate. 
Participant medical information associated with RBR samples is confidential and may 
only be disclosed to third parties as permitted by the ICF (or separate authorization for 
use and disclosure of personal health information) signed by the participant, unless 
permitted or required by law. 
Data derived from RBR sample analysis on individual participants will generally not be 
provided to study Investigators unless a request for research use is granted. The 
aggregate results of any conducted research will be available in accordance with the 
effective Roche policy on study data publication. 
Genetic research data and associated clinical data may be shared with researchers who 
are not participating in the study or submitted to government or other health research 
databases for broad sharing with other researchers. Participants will not be identified by 

 
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name or any other personally identifying information. Given the complexity and 
exploratory nature of these analyses, genetic data and analyses will not be shared with 
Investigators or participants unless required by law. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RBR sample data will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise. 
Monitoring and Oversight Research Biosample Repository 
Samples collected for the RBR will be tracked in a manner consistent with GCP by a 
quality-controlled, auditable, and appropriately validated laboratory information 
management system, to ensure compliance with data confidentiality as well as 
compliance to authorized use of samples as specified in this protocol and in the ICF. The 
Sponsor’s monitors and auditors will have direct access to appropriate parts of records 
relating to participant participation in RBR for the purposes of verifying the data provided 
to the Sponsor. The site will permit monitoring, audits, IRB/EC review, and Health 
Authority inspections by providing direct access to source data and documents related to 
the samples. 
1.5. 
FINANCIAL DISCLOSURE 
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate Health Authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study (i.e., LPLV). 
2. 
DATA HANDLING AND RECORD 
2.1. 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES 
2.1.1. 
Data Quality Assurance 
All participant data relating to the study will be recorded on printed or eCRF unless 
transmitted to the Sponsor or designee electronically (e.g., laboratory data). The 
Investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the case report form (CRF). 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 

 
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Study monitors will perform ongoing source data verification to confirm that data entered 
into the CRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements. 
2.1.3. 
Source Data Records 
Source documents (paper or electronic) are those in which participant data are recorded 
and documented for the first time. They include, but are not limited to, hospital records, 
clinical and office charts, laboratory notes, memoranda, COAs (paper or eCOA), 
evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies of transcriptions that are certified after verification as being accurate 
and complete, microfiche, photographic negatives, microfilm or magnetic media, x-rays, 
participant files, and records kept at pharmacies, laboratories, and medico‑technical 
departments involved in a clinical study. 
Before study initiation, data to be entered directly into the eCRFs (i.e., no prior written or 
electronic record of the data) and considered source data must be defined in the Trial 
Monitoring Plan. 
Source documents that are required to verify the validity and completeness of data 
entered into the eCRFs must not be obliterated or destroyed and must be retained per 
the policy for retention of records described below. 
To facilitate source data verification, the Investigators and institutions must provide the 
Sponsor direct access to applicable source documents and reports for trial‑related 
monitoring, Sponsor audits, and IRB/EC review. The investigational site must also allow 
inspection by applicable Health Authorities. 
2.1.4. 
Use of Computerized Systems 
When clinical observations are entered directly into an investigational site’s 
computerized medical record system (i.e., in lieu of original hardcopy records), the 
electronic record can serve as the source document if the system has been validated in 
accordance with Health Authority requirements pertaining to computerized systems used 
in clinical research. An acceptable computerized data collection system allows 
preservation of the original entry of data. If original data are modified, the system should 
maintain a viewable audit trail that shows the original data as well as the reason for the 
change, name of the person making the change, and date of the change. 

 
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2.1.5. 
 
Safety Biomarker Data 
Adverse Event reports will not be derived from safety biomarker data by the Sponsor, 
and safety biomarker data will not be included in the formal safety analyses for this 
study. In addition, safety biomarker data will not inform decisions on participant 
management. 
2.2. 
RETENTION OF RECORDS 
Records and documents, including signed ICFs, pertaining to the conduct of this study 
must be retained by the Investigator for at least 15 years after study completion or 
discontinuation of the study, or for the length of time required by relevant national or 
local Health Authorities, whichever is longer. After that period, the documents may be 
destroyed, subject to local regulations. No records may be destroyed during the 
retention period without the written approval of the Sponsor. No records may be 
transferred to another location or party without written notification to the Sponsor. 
The Sponsor will retain study data for 25 years after the final study results have been 
reported or for the length of time required by relevant national or local Health Authorities. 
2.3. 
STUDY RECORDS 
The Investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully reconstructed, including but not limited to the protocol, protocol 
amendments, ICFs, and documentation of IRB/EC and governmental approval.  
Roche shall also submit an Annual Safety Report once a year to the IEC and competent 
authorities according to local regulatory requirements and timelines of each country 
participating in the study. 
2.3.1. 
Protocol Amendments 
Any protocol amendments will be prepared by the Sponsor. Protocol amendments will 
be submitted to the IRB/EC and to regulatory authorities in accordance with local 
regulatory requirements. 
Approval must be obtained from the IRB/EC and regulatory authorities (as locally 
required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to participants or any non-substantial changes, as 
defined by regulatory requirements. 
2.3.2. 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the Investigator agrees to submit all manuscripts or abstracts to the Sponsor 
for approval prior to submission. This allows the Sponsor to protect proprietary 
information and to provide comments on the basis of information from other studies that 
may not yet be available to the Investigator. 

 
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The Sponsor will comply with the requirements for publication of study results. In 
accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multi-center studies only in their entirety and not as individual 
center data. In this case, a coordinating Investigator will be designated by mutual 
agreement. 
Any formal publication of the study in which contribution of Sponsor personnel exceeded 
that of conventional monitoring will be considered as a joint publication by the 
Investigator and the appropriate Sponsor personnel. 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors (ICMJE) authorship requirements. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of data from this study will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise. 
2.3.3. 
Dissemination of Clinical Study Data 
Study data may be submitted to government or other health research databases or 
shared with researchers, government agencies, companies, or other groups that are not 
participating in this study. These data may be combined with or linked to other data and 
used for research purposes, to advance science and public health, or for analysis, 
development, and commercialization of products to treat and diagnose disease. In 
addition, redacted clinical study reports and/or other summaries of clinical study results 
may be available in health authority databases for public access, as required by local 
regulation, and will be provided upon request. For more information, refer to the Roche 
Global Policy on Sharing of Clinical Study Information at the following website: 
https://www.roche.com/innovation/process/clinical-trials/data-sharing/ 
Given the complexity and exploratory nature of exploratory biomarker analyses, data 
derived from these analyses will generally not be provided to study Investigators or 
participants unless required by law. The aggregate results of any conducted research 
will be available in accordance with the effective Roche policy on study data publication. 
2.3.4. 
Management of Study Quality 
The Sponsor will implement a system to manage the quality of the study, focusing on 
processes and data that are essential to ensuring participant safety and data integrity. 
Prior to first participant entry into the study, the Sponsor will identify and evaluate 
potential risks associated with critical study processes and data, as well as implement 
controls for the communication, review, and reporting of these risks. Details regarding 
the applied approach for the study will be provided in the integrated Risk Based Quality 
Management Plan. 

 
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Risk control includes the selection of risk-based parameters and establishing associated 
quality tolerance limits. Detection of deviations from defined quality tolerance limits will 
trigger an evaluation to determine if action is needed. Details on the management and 
review of quality tolerance limits will be provided in a separate Quality Tolerance Limit 
plan. 
2.3.5. 
Site Inspections 
Site visits will be conducted by the Sponsor or an authorized representative for 
inspection of study data, participants’ medical records, and eCRFs. The Investigator will 
permit national and local Health Authorities, Sponsor monitors, representatives, and 
collaborators, and the IRBs/ECs to inspect facilities and records relevant to this study. 
3. 
ADMINISTRATIVE STRUCTURE 
Not applicable. 
4. 
STUDY AND SITE CLOSURE 
The Sponsor (or designee) has the right to close the study site or terminate this study at 
any time. Reasons for terminating the study may include, but are not limited to, the 
following: 
 
The incidence or severity of AEs in this or other studies indicates a potential health 
hazard to participants. 
 
Participant enrollment is unsatisfactory. 
 
Emerging data and/or prioritization of assets. 
 
If general study stopping criteria are met, the study will be paused and the Sponsor will 
conduct a full review of all available safety data. The study will resume if the Sponsor 
and Investigator agree and after informing and receiving agreement from relevant Health 
Authorities and Ethics Committees. 
If the study is placed on hold, or if the Sponsor decides to discontinue the study or the 
development program, the Sponsor shall promptly inform the Investigators, the 
IRBs/ECs, the health authorities, and any contract research organizations used for the 
study of the reason for termination or suspension, as specified by the applicable 
regulatory requirements. The Investigators shall promptly inform the participants and 
should ensure appropriate participant therapy and/or follow-up. 
Study sites will be closed upon study completion. A study site is considered closed when 
all required documents and study supplies have been collected and a study site closure 
visit has been performed. 
The Investigator may initiate study site closure at any time, provided there is reasonable 
cause and sufficient notice is given in advance of the intended termination. 

 
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Reasons for the early closure of a study site by the Sponsor or Investigator may include 
but are not limited to: 
 
Failure of the Investigator to comply with the protocol, the requirements of the 
IRB/IEC or local Health Authorities, the Sponsor's procedures, or GCP guidelines. 
 
Inadequate recruitment of participants by the Investigator. 
 
Discontinuation of further study treatment development. 
 

 
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Appendix 2  
Adverse Events: Definitions and Procedures for Evaluating, 
Follow-up and Reporting 
1. 
DEFINITION OF ADVERSE EVENTS 
According to the E2A International Council for Harmonisation (ICH) guideline for Good 
Clinical Practice (GCP), an adverse event (AE) is any untoward medical occurrence in a 
participant or clinical investigation participant administered a pharmaceutical product and 
that does not necessarily have to have a causal relationship with this treatment. 
An AE can therefore be: 
 
Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product. 
 
Events Meeting the AE Definition: 
 
Deterioration in a laboratory value (hematology, clinical chemistry, or urinalysis) or 
other clinical test (e.g., ECG, x-ray) that is associated with symptoms or leads to a 
change in study treatment or concomitant treatment or discontinuation from study 
treatment (see Appendix 3, Section 4). 
 
Exacerbation of a chronic or intermittent preexisting condition, including either an 
increase in frequency and/or intensity of the condition. 
 
New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study. 
 
AEs that are related to a protocol-mandated intervention, including those that occur 
prior to assignment of study treatment (e.g., screening invasive procedures such as 
biopsies). 
 
Events NOT Meeting the AE Definition: 
 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that are associated with the underlying disease, unless judged by the 
Investigator to be more severe than expected for the participant’s condition. 
 
The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
participant’s condition. 
 
Medical or surgical procedure (e.g., endoscopy, appendectomy): The condition that 
leads to the procedure is an AE. 
 
Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 

 
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2. 
DEFINITION OF SERIOUS ADVERSE EVENTS 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
An SAE is defined as any untoward medical occurrence that at any dose: 
 
Results in death. 
 
Is life-threatening. 
The term "life-threatening" in the definition of "serious" refers to an event during 
which the participant was at risk of death at the time of the event; it does not refer to 
an event which hypothetically might have caused death if it was more severe. 
 
Requires inpatient hospitalization or prolongation of existing hospitalization 
(see Appendix 3). 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other 
serious criteria, the event is serious. When in doubt as to whether “hospitalization” 
occurred or was necessary, the AE should be considered serious. 
 
Results in persistent or significant disability/incapacity 
Disability means substantial disruption of the participant’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 (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
 
Is a congenital anomaly/birth defect. 
 
Other significant events: 
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but may 
jeopardize the participant or may require medical or surgical intervention to prevent 
one of the other outcomes listed in the above definition. These events should 
usually be considered serious. 
Examples of such events include  
– 
elevated ALT or AST ( 3  ULN and  3  baseline) in combination with either 
an elevated total bilirubin ( 2  ULN) or clinical jaundice in the absence of 
cholestasis or other causes of hyperbilirubinemia (potential Hy’s law). 

 
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3. 
RECORDING OF ADVERSE EVENT AND/OR SERIOUS 
ADVERSE EVENT 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
The Investigator will then record all relevant AE/SAE information in the electronic case 
report form (eCRF). 
It is not acceptable for the Investigator to send photocopies of the participant’s medical 
records to Medical Monitor in lieu of completion of the eCRF. 
There may be instances when copies of medical records for certain cases are requested 
by the Medical Monitor. In this case, all participant identifiers, with the exception of the 
participant number, will be redacted on the copies of the medical records before 
submission to the Medical Monitor. 
The Investigator will attempt to establish a diagnosis of the event on the basis of signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
3.1. 
ASSESSMENT OF SEVERITY 
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of 
an AE (rated as mild, moderate, severe, or according to a predefined grading criteria) 
(Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events 
[DAIDS]); the event itself may be of relatively minor medical significance (such as severe 
headache without any further findings). 
Severity and seriousness need to be independently assessed for each AE recorded on 
the eCRF. 
SAEs are required to be reported by the Investigator to the Sponsor immediately (i.e., no 
more than 24 hours after learning of the event). 
The adverse event severity grading scale for the DAIDS (v2.1) will be used for assessing 
severity for adverse events. Table 1 will be used for assessing severity for AEs that are 
not specifically listed in the DAIDS. 

 
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Table 1 
DAIDS Adverse Event Severity Grading Scale for Events Not 
Specifically Listed in DAIDS Toxicity Grading Scale 
Grade 
Description 
1 
Mild symptoms causing no or minimal interference with usual social & functional 
activities with intervention not indicated 
2 
Moderate symptoms causing greater than minimal interference with usual social & 
functional activities with intervention indicated 
3 
Severe symptoms causing inability to perform usual social & functional activities with 
intervention or hospitalization indicated  
4 
Potentially life-threatening symptoms causing inability to perform basic self-care 
functions with intervention indicated to prevent permanent impairment, persistent 
disability, or death 
5 
Death 
Abbreviation: DAIDS = Division of AIDS 
Note: Regardless of severity, some events may also meet seriousness criteria. Refer to definition 
of a serious adverse event (see above). DAIDS v2.1 grading scale is available at: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf.  Developed by the 
DAIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health, U.S. 
Department of Health and Human Services. 
 
3.2. 
ASSESSMENT OF CAUSALITY 
Investigators should use their knowledge of the participant, the circumstances 
surrounding the event, and an evaluation of any potential alternative causes to 
determine whether or not an AE is considered to be related to the study treatment, 
indicating "yes" or "no" accordingly. The following guidance should be taken into 
consideration: 
 
Temporal relationship of event onset to the initiation of study treatment. 
 
Course of the event, considering especially the effects of dose reduction, 
discontinuation of study treatment, or reintroduction of study treatment. 
 
Known association of the event with the study treatment or with similar treatments. 
 
Known association of the event with the disease under study. 
 
Presence of risk factors in the participant or use of concomitant medications known 
to increase the occurrence of the event. 
 
Presence of non-treatment-related factors that are known to be associated with the 
occurrence of the event. 
 
For participant receiving combination therapy, causality will be assessed individually for 
each protocol-mandated therapy. 

 
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4. 
FOLLOW-UP OF AES AND SAES 
The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the Medical 
Monitor to elucidate the nature and/or causality of the AE or SAE as fully as possible. 
This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other health care professionals. 
If a participant dies during participation in the study or during a recognized follow-up 
period, when possible the Investigator will provide the Sponsor with a copy of any post-
mortem findings, including histopathology. 
New or updated information will be recorded in the originally completed eCRF. 
The Investigator will submit any updated SAE data to the Sponsor within 24 hours of 
receipt of the information. 
5. 
IMMEDIATE REPORTING REQUIREMENTS FROM 
INVESTIGATOR TO SPONSOR 
Certain events require immediate reporting to allow the Sponsor to take appropriate 
measures to address potential new risks in a clinical study. The Investigator must report 
such events to the Sponsor immediately; under no circumstances should reporting take 
place more than 24 hours after the Investigator learns of the event. The following is a list 
of events that the Investigator must report to the Sponsor within 24 hours after learning 
of the event, regardless of relationship to study treatment: 
 
SAEs 
 
AEs of special interest (AESI; see Section 8.3.6) 
 
Pregnancies (see Section 8.3.5) 
 
The Investigator must report new significant follow-up information for these events to the 
Sponsor immediately (i.e., no more than 24 hours after becoming aware of the 
information). New significant information includes the following: 
 
New signs or symptoms or a change in the diagnosis. 
 
Significant new diagnostic test results. 
 
Change in causality on the basis of new information. 
 
Change in the event’s outcome, including recovery. 
 
Additional narrative information on the clinical course of the event. 
 
Investigators must also comply with local requirements for reporting SAEs to the local 
Health Authority and Institutional Review Board (IRB)/ethics committee (EC). 

 
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5.1 
REPORTING REQUIREMENTS OF SERIOUS ADVERSE 
EVENTS AND ADVERSE EVENTS OF SPECIAL INTEREST 
Events that Occur prior to Study Treatment Initiation 
After informed consent has been obtained but prior to initiation of study treatment, only 
SAEs caused by a protocol-mandated intervention should be reported. The Clinical Trial 
Adverse Event/Special Situations Form provided to Investigators should be completed 
and submitted to the Serious Adverse Event Responsible immediately (i.e., no more 
than 24 hours after learning of the event). 
Events that Occur after Study Treatment Initiation 
For reports of SAEs and AESI (Section 8.3.6) that occur after initiation of study treatment 
(Section 8.3.1), Investigators should record all case details that can be gathered 
immediately (i.e., within 24 hours after learning of the event) on the appropriate Adverse 
Event of Special Interest/Serious Adverse Event eCRF form and submit the report via 
the electronic data capture (EDC) system. A report will be generated and sent to the 
Sponsor’s Safety Risk Management department. 
In the event that the EDC system is unavailable, the Clinical Trial Adverse Event/Special 
Situations Form provided to Investigators should be completed and submitted to the 
Serious Adverse Event Responsible immediately (i.e., no more than 24 hours after 
learning of the event).  
Once the EDC system is available, all information will need to be entered and submitted 
via the EDC system.  
Reporting of Post-Study Adverse Events and Serious Adverse Events 
If the Investigator becomes aware of any other SAE occurring after the end of the AE 
reporting period, and if the event is believed to be related to prior study treatment, the 
event should be reported directly to the Sponsor or its designee, either by faxing or by 
scanning and emailing the Clinical Trial Adverse Event/Special Situations Form using 
the fax number or email address provided to Investigators. 
6. 
SPECIAL SITUATIONS (ACCIDENTAL OVERDOSE OR 
MEDICATION ERROR) 
Accidental overdose and medication error (hereafter collectively referred to as "special 
situations"), are defined as follows: 
 
Accidental overdose: Accidental administration of a drug in a quantity that is higher 
than the assigned dose. 

 
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 
Medication error: Accidental deviation in the administration of a drug (e.g., wrong 
drug, expired drug, accidental overdose, underdose, wrong dosing schedule, 
incorrect route of administration). 
 
After initiation of study drug, special situations associated with RO7565020/matching 
placebo and any associated AEs will be reported until 6 months after the final dose of 
study drug. 
Special situations, regardless of whether they result in an AE, should be recorded on the 
Special Situations eCRF. If there are any associated AEs, each event should be 
recorded separately on the Adverse Event eCRF.  
Special situations and any associated AEs should be reported within 30 days after the 
Investigator becomes aware of the situation. However, if an associated AE fulfills 
seriousness criteria or qualifies as an AE of special interest, both the event and the 
special situation should be reported to the Sponsor immediately (i.e., no more than 
24 hours after the Investigator becomes aware of the event), as described in Section 5.1 
of this appendix.  
7. 
EXPEDITED REPORTING TO HEALTH AUTHORITIES, 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, AND 
ETHICS COMMITTEES 
The Sponsor will promptly evaluate all SAEs and AESIs against cumulative product 
experience to identify and expeditiously communicate possible new safety findings to 
Investigators, IRBs/ ECs, and applicable Health Authorities on the basis of applicable 
legislation. 
To determine reporting requirements for single AE cases, the Sponsor will assess the 
expectedness of these events through use of the reference safety information (RSI) in 
the documents listed below: 
Drug 
Document 
RO7565020 
Investigator's Brochure RO7565020 
RO7565020 placebo 
Investigator's Brochure RO7565020 
  
The Sponsor will compare the severity of each event and the cumulative event 
frequency reported for the study with the severity and frequency reported in the 
applicable reference document. 
Reporting requirements will also be based on the Investigator's assessment of causality 
and seriousness, with allowance for upgrading by the Sponsor as needed. 

 
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Appendix 3  
Procedures for Recording Adverse Events 
Investigators should use correct medical terminology/concepts when recording adverse 
events (AEs) on the Adverse Event electronic case report form (eCRF). Avoid 
colloquialisms and abbreviations. 
Only one AE term should be recorded in the event field on the Adverse Event eCRF. 
1. 
DIAGNOSIS VERSUS SIGNS AND SYMPTOMS 
1.1. 
INFUSION REACTIONS/ INJECTION REACTIONS 
AEs associated with the intravenous infusion or injection that occur during or within 
24 hours after study treatment administration should be captured as individual signs and 
symptoms on the Adverse Event eCRF rather than as an overall diagnosis (e.g., record 
dyspnea and hypotension as separate events rather than a diagnosis of infusion-/ 
injection-related reaction or anaphylactic reaction). 
1.2. 
OTHER ADVERSE EVENTS 
For AEs other than infusion-related or injection reactions, a diagnosis (if known) should 
be recorded on the Adverse Event eCRF rather than individual signs and symptoms 
(e.g., record only liver failure or hepatitis rather than jaundice, asterixis, and elevated 
transaminases). However, if a constellation of signs and/or symptoms cannot be 
medically characterized as a single diagnosis or syndrome at the time of reporting, each 
individual event should be recorded on the Adverse Event eCRF. If a diagnosis is 
subsequently established, all previously reported AEs based on signs and symptoms 
should be nullified and replaced by one AE report that is based on the single diagnosis, 
with a starting date that corresponds to the starting date of the first symptom of the 
eventual diagnosis. 
2. 
ADVERSE EVENTS OCCURRING SECONDARY TO OTHER 
EVENTS 
In general, AEs occurring secondary to other events (e.g., cascade events or clinical 
sequelae) should be identified by their primary cause, with the exception of severe or 
serious secondary events. However, medically significant AEs occurring secondary to an 
initiating event that are separated in time should be recorded as independent events on 
the Adverse Event eCRF. For example: 
 
If vomiting results in mild dehydration with no additional treatment in a healthy adult, 
only vomiting should be reported on the eCRF. 
 
If vomiting results in severe dehydration, both events should be reported separately 
on the eCRF. 
 
If a severe gastrointestinal hemorrhage leads to renal failure, both events should be 
reported separately on the eCRF. 

 
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 
If dizziness leads to a fall and subsequent fracture, all three events should be 
reported separately on the eCRF. 
 
All AEs should be recorded separately on the Adverse Event eCRF if it is unclear as to 
whether the events are associated. 
3. 
PERSISTENT OR RECURRENT ADVERSE EVENTS 
A persistent AE is one that extends continuously, without resolution, between participant 
evaluation timepoints. Such events should only be recorded once on the Adverse Event 
eCRF. The initial severity of the event should be recorded, and the severity should be 
updated to reflect the most extreme severity any time the event worsens. If the event 
becomes serious, the Adverse Event eCRF should be updated to reflect this. 
A recurrent AE is one that resolves between participant evaluation timepoints and 
subsequently recurs. Each recurrence of an AE should be recorded separately on the 
Adverse Event eCRF. 
4. 
ABNORMAL LABORATORY VALUES 
Not every laboratory abnormality qualifies as an AE. A laboratory test result should be 
reported as an AE if it meets any of the following criteria: 
 
Accompanied by clinical symptoms. 
 
Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation). 
 
Results in a medical intervention (e.g., potassium supplementation for hypokalemia) 
or a change in concomitant therapy. 
 
Clinically significant in the Investigator’s judgment. 
 
It is the Investigator’s responsibility to review all laboratory findings. Medical and 
scientific judgment should be exercised in deciding whether an isolated laboratory 
abnormality should be classified as an AE. 
If a clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., alkaline phosphatase and bilirubin 5 times the upper limit of normal [ULN] 
associated with cholecystitis), only the diagnosis (i.e., cholecystitis) should be recorded 
on the Adverse Event eCRF. 
If a clinically significant laboratory abnormality is not a sign of a disease or syndrome, 
the abnormality itself should be recorded on the Adverse Event eCRF, along with a 
descriptor indicating if the test result is above or below the normal range (e.g., "elevated 
potassium," as opposed to "abnormal potassium"). If the laboratory abnormality can be 
characterized by a precise clinical term per standard definitions, the clinical term should 
be recorded as the AE. For example, an elevated serum potassium level of 7.0 mEq/L 
should be recorded as “hyperkalemia.” 

 
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Observations of the same clinically significant laboratory abnormality from visit to visit 
should not be repeatedly recorded on the Adverse Event eCRF, unless the etiology 
changes. The initial severity of the event should be recorded, and the severity or 
seriousness should be updated any time the event worsens. 
5. 
ABNORMAL VITAL SIGN VALUES 
Not every vital sign abnormality qualifies as an AE. A vital sign result should be reported 
as an AE if it meets any of the following criteria: 
 
Accompanied by clinical symptoms. 
 
Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation). 
 
Results in a medical intervention or a change in concomitant therapy. 
 
Clinically significant in the Investigator’s judgment. 
 
It is the Investigator’s responsibility to review all vital sign findings. Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality 
should be classified as an AE. 
If a clinically significant vital sign abnormality is a sign of a disease or syndrome 
(e.g., high blood pressure), only the diagnosis (i.e., hypertension) should be recorded on 
the Adverse Event eCRF. 
Observations of the same clinically significant vital sign abnormality from visit to visit 
should not be repeatedly recorded on the Adverse Event eCRF, unless the etiology 
changes. The initial severity of the event should be recorded, and the severity or 
seriousness should be updated any time the event worsens. 
6. 
ABNORMAL LIVER FUNCTION TESTS 
Parts 1a and 1b: 
The finding of an elevated ALT or AST ( 3  ULN) in combination with either an elevated 
total bilirubin ( 2  ULN) or clinical jaundice in the absence of cholestasis or other 
causes of hyperbilirubinemia is considered to be an indicator of severe liver injury (as 
defined by Hy’s Law). Therefore, Investigators must report as an AE the occurrence of 
either of the following: 
 
Treatment-emergent ALT or AST  3  ULN in combination with total 
bilirubin  2  ULN. 
 
Treatment-emergent ALT or AST  3  ULN in combination with clinical jaundice. 
 
Parts 2 and 3: 
The finding of an elevated ALT or AST in combination with either an elevated total 
bilirubin or clinical jaundice in the absence of cholestasis or other causes of 

 
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hyperbilirubinemia is considered to be an indicator of potential severe liver injury. 
Therefore, Investigators must report as an AE the occurrence of either of the following: 
 
Treatment-emergent ALT or AST  5  ULN value in combination with total 
bilirubin  2  ULN (of which  35% is direct bilirubin). 
 
Treatment-emergent ALT or AST  5  ULN value in combination with clinical 
jaundice. 
 
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal 
laboratory values should be recorded on the Adverse Event eCRF (see Appendix 2) and 
reported to the Sponsor immediately (i.e., no more than 24 hours after learning of the 
event), either as a serious AE (SAE) or a non-serious AE of special interest (see 
Section 8.3.6). 
7. 
DEATHS 
All deaths that occur during the protocol-specified AE reporting period (see Section 5 of 
Appendix 2), regardless of relationship to study treatment, must be recorded on the 
Adverse Event eCRF and immediately reported to the Sponsor. This includes death 
attributed to progression of chronic hepatitis B. 
8. 
PREEXISTING MEDICAL CONDITIONS 
A preexisting medical condition is one that is present at the screening visit for this study. 
Such conditions should be recorded on the General Medical History and Baseline 
Conditions eCRF. 
A preexisting medical condition should be recorded as an AE only if the frequency, 
severity, or character of the condition worsens during the study. When recording such 
events on the Adverse Event eCRF, it is important to convey the concept that the 
preexisting condition has changed by including applicable descriptors (e.g., “more 
frequent headaches”). 
9. 
LACK OF EFFICACY OR WORSENING OF CHRONIC 
HEPATITIS B 
Lack of efficacy in terms of changes in HBsAg does not qualify as an adverse event in 
this study. 
Medical occurrences or symptoms of deterioration in the course of chronic hepatitis B 
should be recorded as an AE if judged by the Investigator to have unexpectedly 
worsened in severity or frequency or changed in nature at any time during the study. 
When recording an unanticipated worsening of chronic hepatitis B on the Adverse Event 
eCRF, it is important to convey the concept that the condition has changed by including 
applicable descriptors (e.g., progression of chronic hepatitis B). 

 
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Hepatitis B virological breakthrough and abnormal liver function tests (see Section 8.3.7) 
should be reported as adverse events. 
10. 
HOSPITALIZATION OR PROLONGED HOSPITALIZATION 
Any AE that results in hospitalization or prolonged hospitalization should be documented 
and reported as an SAE (per the definition of SAEs in Appendix 2), except as outlined 
below. 
An event that leads to hospitalization under the following circumstances should not be 
reported as an AE or an SAE: 
 
Hospitalization for respite care. 
 
Planned hospitalization required by the protocol (e.g., for study treatment 
administration). 
 
Hospitalization for a preexisting condition, provided that all of the following criteria 
are met: 
The hospitalization was planned prior to the study or was scheduled during the 
study (e.g., when elective surgery became necessary because of the expected 
normal progression of the disease). 
The participant has not suffered an AE. 
 
An event that leads to hospitalization under the following circumstances is not 
considered to be an SAE, but should be reported as an AE instead: 
 
Hospitalization for an AE that would ordinarily have been treated in an outpatient 
setting had an outpatient clinic been available. 
 

 
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Appendix 4  
Clinical Laboratory Tests 
Urinalysis, urine pregnancy test, alcohol, cotinine, and drugs of abuse screens will be 
performed locally. The other tests detailed in Table 1 will be performed by the local or 
central laboratory, depending on study parts/cohorts (e.g., for Parts 2 and 3, these tests 
will be performed by central laboratory). If the local laboratory results are used, the 
results must be captured in source documentation and entered into the electronic case 
report form (eCRF) or electronic transfer to the Sponsor. 
For the study parts/cohorts using a central laboratory, local laboratory results may be 
required in the event that the central laboratory results are not available in time for 
determination of study eligibility, study treatment administration and/or response 
evaluation. If a local sample is required, it is important that the sample for central 
analysis be obtained at the same time. Additionally, if the local laboratory results are 
used to make these determinations, the results must be captured in source 
documentation and entered as a comment into the eCRF. 
Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Sections 5.1 and Section 5.2 of the protocol. 
Additional tests may be performed at any time during the study as determined necessary 
by the Investigator or required by local regulations. 
Table 1 
Protocol-Required Safety Laboratory Assessments 
Laboratory Assessments 
Parameters 
Hematology 
 
Leucocytes, erythrocytes, hemoglobin, hematocrit, 
platelets, differential count (neutrophils, eosinophils, 
basophils, monocytes, lymphocytes, mean 
corpuscular hemoglobin [MCH], and mean 
corpuscular hemoglobin concentration [MCHC]). 
Clinical chemistry 
 
Sodium, potassium, chloride, bicarbonate, phosphate, 
magnesium, calcium 
 
Glucose, lipase 
 
Total protein, albumin, total and direct bilirubin, 
alkaline phosphatase, ALT, AST, urate, LDH, gamma-
glutamyl transferase (GGT), creatine kinase/creatine 
phosphokinase (CK/CPK), and amylase 
 
Uric acid, urea, blood urea nitrogen (BUN), creatinine 
and cystatin C, estimated glomerular filtration rate 
(eGFR), calculated creatinine clearance (using the 
Cockcroft Gault formula) 
Coagulation 
 
INR, aPTT, PT. 

 
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Laboratory Assessments 
Parameters 
Viral serology and virology 
 
HIV (specific tests HIV-1 antibody, HIV-2 antibody or 
HIV-1/2 antibody, or any confirmatory test approved 
by Health Authorities), hepatitis A virus (HAV IgM 
antibody), hepatitis B surface antigen (HBsAg) 
quantitative, hepatitis B surface antibody (HBsAb) 
quantitative, hepatitis C virus (HCV) antibody, HCV 
RNA (if HCV antibody positive), hepatitis D virus 
(HDV) antibody (Parts 2 and 3 only), hepatitis E virus 
(HEV) antibody or HEV RNA (Parts 2 and 3 only).  
 
HBV DNA quantitative 
Lipids 
 
Cholesterol, LDL cholesterol, HDL cholesterol, 
triglycerides. 
Thyroid hormones 
 
Free T4, TSH, free T3. 
Pregnancy test 
 
All biological female participants will have a blood 
pregnancy test at screening (in Parts 2 and 3, if two 
tests at screening, the one within 14 days before 
dosing should be a blood test). Urine pregnancy tests 
will be performed at specified subsequent visits. If a 
urine pregnancy test is positive, it must be confirmed 
by a blood pregnancy test. 
Urinalysis 
 
Specific gravity. 
 
Dipstick: pH, glucose, protein, blood, ketones, 
bilirubin, urobilinogen, nitrite, leukocyte esterase. 
 
If there is a clinically significant positive result, urine 
will be sent to the laboratory for microscopy and 
culture. If there is an explanation for the positive 
dipstick results (e.g., menses), it should be recorded, 
and there is no need to perform microscopy and 
culture. 
 
Microscopic examination (RBCs, WBCs, casts, 
crystals, epithelial cells, bacteria), if blood or protein is 
abnormal 
Other screening tests 
 
Urine drug abuse screen, including cannabinoids, 
amphetamines and/or methamphetamines, opiates, 
methadone, cocaine, benzodiazepines, and 
barbiturates 
 
Urine cotinine test 
 
Alcohol test (breath or urine) 
Others 
 
Auto-antibodies (ANA, AMA, ASMA, a-TPO) 
 
C3, C4, and total hemolytic complements (CH50) 
 
C-reaction protein (CRP) 
 
Glutamate dehydrogenase (GLDH) for Parts 2 and 3 
(exploratory) 
 
-fetoprotein 
Abbreviations: ALT = alanine aminotransferase; AMA = antimitochondrial antibody; 
ANA = antinuclear antibody; aPTT = activated partial thromboplastin time; ASMA = anti-
smooth muscle antibody; AST = aspartate aminotransferase; a-TPO = anti-thyroid peroxidase; 
HDL = high-density lipoprotein; INR = international normalized ratio; LDH = lactate 
dehydrogenase; LDL = low-density lipoprotein; PT = prothrombin time; RBC = red blood cell; 
TSH = thyroid-stimulating hormone; WBC = white blood cell. 
  

 
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Results of clinical laboratory testing will be recorded on the eCRF or be received as 
electronically produced laboratory reports submitted directly from the local or central 
laboratory. 
Investigators must document their review of each laboratory safety report. 
Laboratory/analyte results that could unblind the study will not be reported to 
investigative sites or other blinded personnel until the study has been unblinded. 
Additional Statistical Considerations for Clinical Laboratory Data 
Standard Reference Ranges and Transformation of Data 
Potential analysis considerations for analyzing laboratory data includes the use of 
standard reference ranges and potential transformation of data for specific laboratory 
tests.  
In this scenario, Roche standard reference ranges, rather than the reference ranges of 
the Investigator, can be used for specific parameters. For these parameters, the 
measured laboratory test result will be assessed directly using the Roche standard 
reference range. Certain laboratory parameters will be transformed to Roche’s standard 
reference ranges. 
A transformation will be performed on certain laboratory tests that lack sufficiently 
common procedures and have a wide range of Investigator ranges, e.g., enzyme tests 
that include AST, ALT, alkaline phosphatase, and total bilirubin. The standard reference 
ranges for these parameters have a lower limit of zero; therefore, only the upper limits of 
the ranges will be used in transforming the data. 
Definition of Laboratory Abnormalities 
For all laboratory parameters included in the analysis described above, there exists a 
Roche predefined standard reference range. Laboratory values falling outside this 
standard reference range will be labeled “H” for high or “L” for low in participant 
statistical outputs of laboratory data. 
In addition to the standard reference range, a marked reference range has been 
predefined by Roche for these laboratory parameters. The marked reference range is 
broader than the standard reference range. Values falling outside the marked reference 
range that also represent a defined change from baseline will be considered marked 
laboratory abnormalities (i.e., potentially clinically relevant). If a baseline value is not 
available for a participant, the midpoint of the standard reference range will be used as 
the participant’s baseline value for the purposes of determining marked laboratory 
abnormalities. Marked laboratory abnormalities will be labeled in the participant listings 
as “HH” for very high or “LL” for very low. 

 
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Appendix 5  
Contraceptive and Barrier Methods Guidance 
1. 
DEFINITIONS 
 
Participant of Childbearing Potential (POCBP) 
A participant is considered fertile following menarche and until becoming 
postmenopausal unless permanently sterile. The definition of childbearing potential may 
be adapted for alignment with local guidelines or requirements. 
 
Participants in the following categories are considered to be of 
Non-Childbearing Potential (PONCBP) 
o 
Pre-menarchal 
o 
Premenopausal biological females with one of the following: 
 
Documented hysterectomy. 
 
Documented bilateral salpingectomy. 
 
Documented bilateral oophorectomy. 
Note: Documentation can come from the site personnel’s: review of participant’s 
medical records, medical examination, or medical history interview. 
o 
Postmenopausal participants: 
 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause other than menopause. A high follicle-stimulating 
hormone (FSH) level in the postmenopausal range may be used to confirm a 
postmenopausal state in participants not using hormonal contraception or 
hormonal replacement therapy (HRT). However, in the absence of 12 months of 
amenorrhea, a single FSH measurement is insufficient. 
 
Participants on HRT and whose menopausal status is in doubt will be required 
to use one of the non-hormonal, highly effective contraception methods if they 
wish to continue their HRT during the study. Only discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
 
2. 
CONTRACEPTION GUIDANCE 
 
Biological Female Participants 
POCBP are eligible to participate if they agree to use highly effective method of 
contraception that results in a failure rate of  1% per year until 24 weeks after the final 
dose of study treatment, consistently and correctly as described in Table 1 below. 
Per International Council for Harmonisation (ICH) M3(R2), highly effective methods of 
birth control are defined as those, alone or in combination, that result in a low failure rate 

 
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(i.e., less than 1% per year) when used consistently and correctly as described in 
Table 1 below.  
Table 1 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User-Dependenta 
(Failure rate of  1% per year when used consistently and correctly) 
 
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation: 
o 
Oral 
o 
Intravaginal 
o 
Transdermal 
 
Progestogen-only hormonal contraception associated with inhibition of ovulation: 
o 
Oral 
o 
Injectable  
Highly Effective Methods That Are User-Independent 
(Failure rate of  1% per year) 
 
Implantable progestogen-only hormonal contraception associated with inhibition of 
ovulationa 
 
Intrauterine device 
 
Intrauterine hormone-releasing system 
 
Bilateral tubal occlusion/ligation 
Azoospermic partner (vasectomized or due to medical cause) 
A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the POCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used. 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the study 
and the preferred and usual lifestyle of the participant. 
Effective Birth Control Methods Which May Not Be Considered As Highly Effective 
(Failure rate of  1% per year when used consistently and correctly) 
 
Progestogen-only oral hormonal contraception, where inhibition of ovulation is not the 
primary mode of action 
 
Male or female condom with or without spermicideb 
 
Cap, diaphragm, or sponge with spermicideb 

 
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Abbreviation: POCBP = Participant of childbearing potential. 
a) Hormonal contraception may be susceptible to interaction with the study treatment, which 
may reduce the efficacy of the contraception method. 
Typical use failure rates may differ from those when used consistently and correctly. Use 
should be consistent with local regulations regarding the use of contraceptive methods for 
participants participating in clinical studies. 
b) A combination of male condom with either cap, diaphragm, or sponge with spermicide 
(double-barrier methods) are also considered acceptable, but not highly effective, birth 
control methods (i.e., when the risk of teratogenicity and genotoxicity is unlikely). 
 
3. 
PREGNANCY TESTING 
For POCBP enrolled in the study, blood sample and urine pregnancy tests will be 
performed according to the SoA (see Section 1.3). If a highly sensitive urine pregnancy 
test is positive, it must be confirmed by a blood pregnancy test. 
Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected and according to local practice. 
4. 
COLLECTION OF PREGNANCY INFORMATION 
 
Male participants with partners who become pregnant 
The Investigator will attempt to collect pregnancy information on any male participant’s 
partner who becomes pregnant while the male participant is in this study or within 
6 months after the final dose of study treatment (see Section 8.3.5 Pregnancy). This 
applies only to male participants who receive RO7565020. 
Attempts should be made to collect and report details of the course and outcome of any 
pregnancy in the partner of a male participant exposed to study treatment. The 
Investigator will record pregnancy information on the Clinical Trial Pregnancy Reporting 
Form and submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy. 
When permitted by the site, the pregnant partner would need to sign an Authorization for 
Use and Disclosure of Pregnancy Health Information and an Authorization for Use and 
Disclosure of Infant Health Information to allow for follow-up on her pregnancy and the 
infant health information respectively. If the authorization has been signed, the 
Investigator should update the Clinical Trial Pregnancy Reporting Form with additional 
information on the course and outcome of the pregnancy when available.  
An Investigator who is contacted by the male participant or his pregnant partner may 
provide information on the risks of the pregnancy and the possible effects on the fetus, 
to support an informed decision in cooperation with the treating physician and/or 
obstetrician. The partner will be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the Sponsor. 
Monitoring of the participant’s partner should continue until conclusion of the pregnancy. 

 
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Any termination of the pregnancy will be reported, regardless of fetal status (presence or 
absence of anomalies) or indication for procedure. 
Information on the status of the infant health at the 6th and 12th month after the date of 
birth will be forwarded to the Sponsor by using Infant Clinical Trial Follow-up Reporting 
Form when the authorization for infant health follow-up has been obtained. 
 
Participants who become pregnant 
The Investigator will collect pregnancy information on any participant who becomes 
pregnant while participating in this study (see Section 8.3.5 Pregnancy). Information will 
be recorded on the Clinical Trial Pregnancy Reporting Form and submitted to the 
Sponsor within 24 hours of learning of a participant's pregnancy. The participant will be 
followed to determine the outcome of the pregnancy. Monitoring of the participant should 
continue until conclusion of the pregnancy. Any termination of pregnancy will be 
reported, regardless of fetal status (presence or absence of anomalies) or indication for 
procedure. The Investigator will collect follow-up information on the participant and the 
neonate which will be forwarded to the Sponsor. When permitted by the site, the 
pregnant participant would need to sign an Authorization for the Use and Disclosure of 
Infant Health Information to allow for follow-up on the infant. Information on the status of 
the infant health at the 6th and 12th month after the date of birth will be forwarded to the 
Sponsor by using Infant Clinical Trial Follow-up Reporting Form when the authorization 
for infant health follow-up has been obtained.  
While pregnancy itself is not considered to be an adverse event (AE) or serious AE 
(SAE) and should not be recorded on the AE eCRF, any pregnancy complication will be 
reported as an AE or SAE. A spontaneous abortion is always considered to be an SAE 
and will be reported as such. Any post-study, pregnancy-related SAE considered 
reasonably related to the study treatment by the Investigator will be reported to the 
Sponsor as described in Appendix 2. While the Investigator is not obligated to actively 
seek this information in former study participants, he/she may learn of an SAE through 
spontaneous reporting. 
Any participant who becomes pregnant while participating in the study will discontinue 
study treatment. 
Additionally, attempts should be made to collect and report infant health information. 
When permitted by the site, an Authorization for the Use and Disclosure of Infant Health 
Information would need to be signed by one or both parents (as per local regulations) to 
allow for follow-up on the infant. If the authorization has been signed, the infant's health 
status at birth should be recorded on the Clinical Trial Pregnancy Reporting Form. In 
addition, the Sponsor may collect follow-up information on the infant's health status at 
6 and 12 months after birth. 

 
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5 
ABORTIONS 
Any spontaneous abortion in a participant exposed to study treatment or the partner of a 
male participant exposed to study treatment should be classified as an SAE (as the 
Sponsor considers spontaneous abortions to be medically significant events), recorded 
on the Adverse Event eCRF, and reported to the Sponsor immediately (i.e., no more 
than 24 hours after learning of the event; see Section 5 of Appendix 2). 
Any induced abortion due to maternal toxicity and/or embryofetal toxicity should also be 
classified as an SAE, recorded on the Adverse Event eCRF, and reported to the 
Sponsor immediately (i.e., no more than 24 hours after learning of the event; see 
Section 5 of Appendix 2). 
Elective or therapeutic abortion not associated with an underlying maternal or 
embryofetal toxicity (e.g., induced abortion for personal reasons) does not require 
expedited reporting and is not considered an AE but should be reported as outcome of 
pregnancy on the Clinical Trial Pregnancy Reporting Form. 
All abortions should be reported as pregnancy outcomes on the paper Clinical Trial 
Pregnancy Reporting Form.  
6 
CONGENITAL ANOMALIES/BIRTH DEFECTS 
Any congenital anomaly/birth defect in a child born to a participant or partner of a male 
participant exposed to study treatment should be classified as an SAE, recorded on the 
Adverse Event eCRF, and reported to the Sponsor immediately (i.e., no more than 24 
hours after learning of the event). 

 
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Appendix 6  
Investigational Medicinal Product and Non-Investigational 
Medicinal Product Designations 
Table 1 
Investigational, Authorized Auxiliary, and Unauthorized 
Auxiliary Medicinal Product Designations for European 
Economic Area 
Product Name 
IMP/AxMP Designation 
Marketing 
Authorization Status in 
EEA 
Used within 
Marketing 
Authorization 
RO7565020 
IMP (test product) 
Unauthorized 
Not applicable 
RO7565020 
placebo 
IMP (placebo) 
Unauthorized 
Not applicable 
ETV 
Authorized AxMP 
(background treatment) 
Authorized 
Yes 
TDF 
Authorized AxMP 
(background treatment) 
Authorized 
Yes 
TAF 
Authorized AxMP 
(background treatment) 
Authorized 
Yes 
Abbreviations: AxMP = auxiliary medicinal product; EEA = European Economic Area; 
ETV = entecavir; IMP = investigational medicinal product; TAF = tenofovir alafenamide; 
TDF = tenofovir disoproxil fumarate. 
 
Table 2 
Investigational and Non-Investigational Medicinal Product 
Designations for the United Kingdom 
Product Name 
IMP/NIMP 
Designation 
Marketing 
Authorization Status 
in the UK 
Used within Marketing 
Authorization 
RO7565020 
IMP (test product) 
Unauthorized 
Not applicable 
RO7565020 
placebo 
IMP (placebo) 
Unauthorized 
Not applicable 
ETV 
NIMP (background 
treatment) 
Authorized 
Yes 
TDF 
NIMP (background 
treatment) 
Authorized 
Yes 
TAF 
NIMP (background 
treatment) 
Authorized 
Yes 
Abbreviations: ETV = entecavir; IMP = investigational medicinal product; NIMP = non-
investigational medicinal product; TAF = tenofovir alafenamide; TDF = tenofovir disoproxil 
fumarate, UK = United Kingdom. 
 

 
RO7565020—F. Hoffmann-La Roche Ltd 
130/Protocol BP44118, Version 3 
Appendix 7  
Abbreviations 
Abbreviation 
Definition 
AAV 
adeno-associated virus 
Ab 
antibody 
ADA 
anti-drug antibody 
ADCP 
antibody-dependent cellular phagocytosis 
AE 
adverse event 
AESI 
adverse event of special interest 
AFP 
-fetoprotein 
ALT 
alanine aminotransferase 
AMA 
antimitochondrial antibody 
ANA 
antinuclear antibody 
ARFI 
acoustic radiation force impulse 
ASMA 
anti-smooth muscle antibody 
AST 
aspartate aminotransferase 
a-TPO 
anti-thyroperoxidase 
AUC0-21d 
area under the time-concentration curve from 0 to 
21 days 
AUCinf 
area under the time-concentration curve from 0 to 
infinity 
AUClast 
area under the time-concentration curve from 0 to last 
sampling point or last quantifiable sample, whichever 
comes first 
AUCtau 
area under the time-concentration curve within a 
dosing interval 
AxMP 
auxiliary medicinal product 
BMI 
body mass index 
cccDNA 
covalently closed circular DNA 
CHB 
chronic hepatitis B 
CL 
clearance 
CL/F 
apparent clearance 
Cmax 
maximum concentration 
COVID-19 
coronavirus disease 2019 
CSR 
clinical study report 
DAIDS 
Division of AIDS 
DBP 
diastolic blood pressure 
DDT 
Dose Decision Team 
DEP 
Dose Escalation Plan 

 
RO7565020—F. Hoffmann-La Roche Ltd 
131/Protocol BP44118, Version 3 
DNA 
deoxyribonucleic acid 
EASL 
European Association for the Study of the Liver 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
eTMF 
electronic trial master file 
ETV 
entecavir 
E.U. 
European Union 
FcRn 
neonatal Fc receptor 
FIH 
First-in-human 
HAV 
hepatitis A virus 
HBcAg 
hepatitis B core antigen 
HBcrAg 
hepatitis B core-related antigen 
HBeAg 
hepatitis B e antigen 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCC 
hepatocellular carcinoma 
HCV 
hepatitis C virus 
HDV 
hepatitis D virus 
HEV 
hepatitis E virus 
HIV 
human immunodeficiency virus 
HLA 
human leukocyte antigen 
HSV 
herpes simplex virus 
IA 
interim analysis 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IFN 
interferon 
IgG 
immunoglobulin G 
IgM 
immunoglobulin M 
IL 
interleukin 
IMP 
investigational medicinal product 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IRR 
infusion-/injection-related reaction 
IV 
intravenous 
IxRS 
interactive (voice/web) response system 
LLN 
lower limit of normal 

 
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132/Protocol BP44118, Version 3 
LLOQ 
lower limit of quantification 
LPLO 
last participant, last observation 
mAb 
monoclonal antibody 
MRI 
magnetic resonance imaging 
NIMP 
non-investigational medicinal products 
NK 
natural killer 
NOAEL 
no-observed-adverse-effect level 
NUC 
nucleos(t)ide analogue 
OTC 
over-the-counter 
PBMC 
peripheral blood mononuclear cell 
PBPK 
physiologically-based pharmacokinetic 
PD 
pharmacodynamic 
PEG 
pegylated 
PK 
pharmacokinetic 
POCBP 
participant of childbearing potential 
PONCBP 
participant of non-childbearing potential 
popPK 
population pharmacokinetic 
QTcF 
QT corrected for heart rate using the Fridericia’s 
correction factor 
RBR 
Research Biosample Repository 
RNA 
ribonucleic acid 
RUO 
research-use-only 
SAD 
single-ascending dose 
SAE 
serious adverse event 
SBP 
systolic blood pressure 
SC 
subcutaneous 
scRNAseq 
single-cell RNA sequencing 
siRNA 
short interfering RNA 
SoA 
schedule of activities 
SOP 
standard operating procedure 
SUSAR 
suspected unexpected serious adverse reactions 
SVP 
subviral particle 
t1/2 
terminal half-life 
TAF 
tenofovir alafenamide 
TDF 
tenofovir disoproxil fumarate 
tmax 
time of maximum concentration observed 
TMDD 
target-mediated drug disposition 
TNF 
tumor necrosis factor 

 
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TSH 
thyroid-stimulating hormone 
ULN 
upper limit of normal 
U.S. 
United States 
Vss 
volume of distribution 
Vz/F 
apparent volume of distribution 
WHO 
World Health Organization 
YTE 
M252Y/S254T/T256E (mutation) 
 

Signature Page for Protocol - BP44118 - HBSAG MAB - v3 - Global/Core - Published
System identifier: RIM-CLIN-487278
Approval Task
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15-May-2023 18:04:28 GMT+0000