CHRONIC HEPATITIS B VIRUS INFECTION

Taiwan only participated in the second part of this trial. The purpose of Part 2 is to understand whether RO7239958 is safe and well tolerated, how it is absorbed and eliminated from the body (so-called pharmacokinetics [pharmacokinetics, PK]), and how it affects hepatitis B virus (so-called drug Efficacy [pharmacodynamics, PD]). During the trial, you will be carefully monitored, and blood and urine samples will be collected regularly to help understand the safety, PK and PD effects of RO7239958. There is no independent subject consent form (ICF) for PK testing, and participation is mandatory.

RO7239958

RO7239958

100 mg/mL

Incidence, severity, and causal relationship of adverse events (AEs).
 Changes in vital signs, physical findings and electrocardiogram (ECG)
findings, and clinical laboratory results during and following RO7239958 administration.
 Incidence of injection site reactions (ISRs).
Plasma and urine PK parameters determined using non-compartmental analysis (NCA).
 The following plasma PK parameters will be calculated:
o Time to maximum concentration (Tmax).
o Maximum plasma concentration observed (Cmax).
o Area under the curve (AUC) for various time intervals post-dose.
 Additional PK parameters may be calculated in plasma (e.g., apparent clearance [CL/F], terminal half-life [t1/2],
K [elimination rate constant]).
 Additional urine parameters may be calculated, e.g., cumulative amount of drug excreted in urine over defined
time periods (Ae).
 Time course profile of HBsAg levels and maximum decline from baseline.
 Time course profile of hepatitis B surface antibody (anti-HBs) levels.

ALL STUDY PARTS
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. Participant must be 18 to 65 years of age inclusive, at the time of signing the informed consent.
Weight:
3. Body weight of at least 45 kg and maximally 150 kg, and BMI within the range of 18 to 32 kg/m2 (inclusive).
Sex:
4. Male and female participants:
The contraception and abstinence requirements are intended to prevent exposure of an
embryo to the study treatment. The reliability of sexual abstinence to meet enrolment
eligibility 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 of
contraception.
a) Female participants: Should be women of non-childbearing potential (WONCBP).
b) Male participants: During the treatment period and for at least 105 days after the last
dose of RO7239958 or placebo, agreement to:
i. With partners who are women of childbearing potential (WOCBP): Remain
abstinent (refrain from heterosexual intercourse) or use contraceptive
measures such as a condom plus an additional contraceptive method that
together result in a failure rate of < 1% per year.
ii. With pregnant female partners, remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures such as a condom to avoid
exposing the embryo.
iii. Refrain from donating sperm for at least 105 days after last dose of
RO7239958 or placebo.
PART 1 (SAD HV) ONLY
Type of participants:
1. Healthy, as judged by the Investigator. Healthy status will be defined as the absence of
evidence of any active or chronic disease following a detailed medical and surgical history,
concomitant drug use (including hormonal supplements), a complete physical examination
including vital signs, 12-lead ECG, hematology, blood chemistry, serology, and urinalysis.
Others Inclusions:
2. Non-smoker (nor tobacco containing products) for at least 90 days prior to dosing on Day 1,
and agrees to remain non-smoker during the study.
PART 2 (CHB) ONLY
Type of Participants and Disease Characteristics
1. Positive serum HBsAg status for > 6 months prior to screening.
2. Serum HBsAg level  250 IU/mL at screening.
3. On stable entecavir or tenofovir (alone or in combination) treatment, and having received the
same NUC in the 3 months prior to randomisation, and expected to remain on the same
NUC for the duration of study participation.
4. HBV DNA below the lower limit of quantification (LLQ) for ≥ 6 months prior to screening by
local testing, and confirmed at screening.
5. Screening laboratory values (including hematology, chemistry, urinalysis) within normal
ranges, or judged to be not clinically significant by the Investigator and Medical Monitor, and:
a) Screening alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
 2 × upper limit of normal (ULN), confirmed between Day -7 to Day -4.
b) Screening -glutamyltransferase (GGT) and alkaline phosphatase (ALP)  ULN, and
normal values of prothrombin time (PT), INR, and activated partial thromboplastin time
(aPTT).
c) Screening total bilirubin of  ULN (Note: isolated bilirubin  1.5  ULN is acceptable for
patients with Gilbert’s syndrome).
d) Screening neutrophil count  1500 cells/mm3
(Note:  1200 cells/mm3
is acceptable in
participants of black race).
e) Screening hemoglobin  11 g/dL in females and  12.5 g/dL in males.
f) Screening platelet count  150,000 cells/mcL.
6. No past or current diagnosis of cirrhosis. Transient elastography at screening showing a kPa
value consistent with a degree of liver fibrosis not higher than F3. By FibroScan, a cut-off of
< 8.5 kPa in the fasted status (last meal  3 hours prior) is recommended.

Medical Conditions
1. Participants who have donated over 500 mL of blood or blood products or had significant
blood loss within three months prior to screening.
PART 1 (SAD HV) ONLY:
Medical Conditions
1. History or presence of significant (as judged by the investigator) cardiovascular, respiratory,
hepatic, renal, gastrointestinal, endocrine, haematological disorders, or diagnosed central or
peripheral neurological disease, capable of significantly altering the absorption, metabolism,
or elimination of drugs, or constituting a risk when taking the study treatment, or of interfering
with the interpretation of the data.
2. Screening ECG showing clinically relevant abnormalities (including arrhythmias or marked
QT abnormalities [QTcF < 300 msec or > 450 msec], or other cardiac abnormalities that are
considered clinically significant by the Investigator. Known risk factors for Torsade de
Pointes (e.g., hypokalemia, heart failure), or a personal or family history of congenital long
QT syndrome.
3. Abnormal blood pressure: supine systolic blood pressure (SBP) <90 mmHg or >140mmHg
or diastolic blood pressure (DBP) <45mmHg or >90mmHg at the time of screening and at
Day -1, confirmed by two consecutive triplicate measurements, properly measured with wellmaintained equipment.
4. History of lymphoma, leukaemia, or malignancy within the past five years, except for
squamous epithelial carcinomas of the skin that have been resected with no evidence of
metastatic disease for three years.
5. History or presence of liver disease, or known hepatic or biliary abnormalities (with the
exception of Gilbert’s syndrome or asymptomatic gallstones).
6. ALT ≥1.5  ULN at screening and at Day 1.
7. Any clinically significant out of range findings in other laboratory test results or any other
clinically significant (as judged by the Investigator) abnormalities in the physical examination
at screening and on Day -1.
8. Sensitivity to any of the study treatments, or components thereof, or drug or other allergy
that, in the opinion of the Investigator, contraindicates the participation in the study.
9. Any clinically relevant history of hypersensitivity or allergic reactions, either spontaneous or
following drug administration, or exposure to foods or environmental agents.
10. Any major illness within one month preceding the screening visit, or any febrile illness within
the two weeks preceding the screening visit.
11. Concomitant disease or condition that could interfere with, or treatment of which might
interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose
an unacceptable risk to the participant in this study.
Prior/Concomitant Therapy
12. Used or intend to use of over-the-counter (OTC) or prescription medication (including herbal
and traditional remedies) before study start and during the study as described in list of
prohibited medications.
13. Live vaccine(s) within 28 days of screening, or plans to receive live vaccines during the
study or within 28 days of the last dose.
14. Likely to need concomitant medication during the study period.
15. Treatment with biologic agents (such as monoclonal antibodies, including marketed drugs)
within three months or five half-lives (whichever is longer) prior to dosing.
Prior/Concurrent Clinical Study Experience
16. Currently enrolled in or have participated within the last 90 days or five times the half-life of
the investigational drug (whichever is longer) from signing of consent in this or any other
clinical study involving an investigational product or in any other type of medical research.
17. Exposure to more than four new chemical entities within 12 months prior to the first dosing
day.
Diagnostic Assessments
18. Known positive for hepatitis B surface antigen (HBsAg), or hepatitis B core total antibody
[anti-HBc]), or hepatitis C virus (HCV) antibody test result at screening.
19. Known positive for human immunodeficiency virus (HIV) infection and/or positive for HIV
infection at screening.
20. Positive pre-study drugs and alcohol screen.
Other Exclusions
21. History or evidence of alcohol abuse (consumption of more than two standard drinks per day
on average; one standard drink equals 10 grams of alcohol), and/or drug abuse within one
year of screening.
22. Any suspicion or history of substance abuse or dependence.
23. Dietary restrictions that would prohibit the consumption of standardised meal.
24. Healthy participants under judicial supervision, guardianship or curatorship.
PART 2 (CHB) ONLY
Medical Conditions
1. History or presence of significant (as judged by the Investigator) cardiovascular (including
poorly controlled blood hypertension), respiratory, hepatic, renal, gastrointestinal, endocrine,
haematological disorders, or diagnosed central or peripheral neurological disease, capable
of altering the absorption, metabolism, or elimination of drugs, or constituting a risk when
taking the study treatment, or of interfering with the interpretation of the data.
2. History or presence of bridging fibrosis or cirrhosis or decompensated liver disease.
3. History or presence of a medical condition associated with liver disease other than HBV
infection (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin
exposure, thalassemia, non-alcoholic steatohepatitis). Other known hepatic or biliary
abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
4. History of or suspicion of hepatocellular carcinoma or alpha fetoprotein (AFP) 13 ng/mL at
screening.
5. History of lymphoma, leukaemia, or malignancy within the past five years, except for
squamous epithelial carcinomas of the skin that have been resected with no evidence of
metastatic disease for three years.
6. History of having received (in the last six months) or currently receiving any systemic antineoplastic (including radiation) or immune-modulatory treatment (including systemic
corticosteroids).
7. History of organ transplantation.
8. Any major illness within one month preceding the screening visit, or any febrile illness within
the two weeks preceding randomisation.
9. Clinically significant (multiple or severe) drug allergies, or intolerance to topical
corticosteroids, or history of severe post-treatment hypersensitivity reactions (including, but
not limited to, erythema multiforme major, linear IgA dermatosis, toxic epidermal necrolysis,
or exfoliative dermatitis).
10. Estimated glomerular filtration rate (eGFR) < 70 mL/min/1.73m2
(CKD-epi equation).
11. Confirmed QT interval corrected using Fridericia’s formula (QTcF) 450 ms. Patients with
correctable risk factors for prolonged QT (e.g., electrolyte abnormalities) can be re-assessed
after correction of the risk factor(s).
Prior/Concomitant Therapy
12. Live vaccine(s) within 28 days of screening, or plans to receive live vaccines during the
study or within 28 days of the last dose.
13. Expected to need any other systemic antiviral therapy at any time during participation in the
study, with the exception of current NUC treatment and / or oral/ topical therapy for Herpes
Simplex Virus (HSV).
Prior/Concurrent Clinical Study Experience
14. Currently enrolled in or have participated, within the last 90 days or five times the half-life of
the investigational drug (whichever is longer) from signing of consent in this or any other
clinical study involving an investigational product or in any other type of medical research.
Diagnostic Assessments
15. Positive hepatitis C antibody at screening.
16. Known positive for human immunodeficiency virus (HIV) infection and/or positive for HIV
infection at screening.
17. Positive pre-study treatment/alcohol screen.
Other Exclusions
18. History or evidence of alcohol abuse (consumption of more than two standard drinks per day
on average; one standard drink equals 10 grams of alcohol) and/or drug abuse within one
year of screening; positive test result for drugs of abuse at screening.
19. Patients under judicial supervision, guardianship or curatorship.
20. Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that,
in the opinion of the Investigator contraindicates the participation in the study.