HEPATITIS B VIRUS

The YP39364 test is the first test conducted in humans and consists of three parts.The first and second parts are random assignment, sponsor openness, trial host blindness, and subject blindness.The third part of the trial is a non-randomized, non-controlled, open trial. In Taiwan, only Part 2 and Part 3 will be included in the subjects. The second part of the trial will evaluate the safety, tolerability, PK and PD of oral administration of RO7049389 to patients with chronic HBV infection. The third part of the trial is an open, adaptable, multi-group trial, which aims to evaluate the safety, tolerability, and safety of patients with chronic hepatitis B (CHB) who are inhibited by NUC or who have not received treatment after oral administration of RO7049389 outside of SoC. PK, PD and efficacy (NUC with/without Peg-IFN).

RO7049389

RO7049389

50, 200 & 500

The primary objectives of Part 2 (patients chronically infected with HBV) of this studyare as follows:
• To assess the safety and tolerability of 4 weeks of treatment with RO7049389.
• To investigate the antiviral effect (quantitative HBV DNA level) of 4 weeks of treatment with RO7049389.
The secondary objective of Part 2 of this study is:
• To investigate the plasma PK of RO7049389.
The exploratory objectives of Part 2 of this study are as follows:
• To investigate the response relationship between RO7049389 exposure and HBV DNA
• To explore other viral response outcomes (e.g. quantitative HBeAg, loss of HBeAg,
HBeAg seroconversion, quantitative HBsAg, HBsAg loss, HBsAg seroconversion)
after of 4 weeks of treatment with RO7049389
• Exploratory liver biomarkers will be examined.

1. Adult male and female patients, 18 to 60 years of age, inclusive. (Patients
aged 20 years and above will be recruited in Taiwan)
2. A BMI between 18 to 30 kg/m2 inclusive.
3. Chronic hepatitis B infection, defined as positive test for HBsAg for more than
6 months prior to randomization.
4. HBV DNA at screening ≥ 2 × 104 IU/mL for HBeAg positive patients, or ≥ 2 ×
103 IU/mL for HBeAg-negative patients.
5. ALT at screening ≤ 5 × upper limit of normal (ULN; both immune tolerant
and immune active patients).
6. Screening laboratory values (hematology, chemistry [other than liver function
test], urinalysis) obtained up to 28 days prior to first study treatment within
acceptable range or judged to be not clinically significant by the Investigator
and the Sponsor.
7. Liver biopsy, fibroscan or equivalent test obtained within the past 6 months demonstrating liver disease consistent with chronic HBV infection with
absence of extensive bridging fibrosis and absence of cirrhosis (cutoff for
fibroscan 8.5 kPa or Metavir fibrotic Stage ≥ 3 or other equivalent staging systems).
8. For men: agreement to remain abstinent (refrain from heterosexual
intercourse) or use contraceptive measures, and agreement to refrain from
donating sperm, as defined below:
a. With female partners of childbearing potential or pregnant female
partners, men must remain abstinent or use a condom during the
treatment period and for at least 28 days after the last dose of study
drug to avoid exposing the embryo. Men must refrain from donating
sperm during this same period.
b. The reliability of sexual abstinence should be evaluated in relation to
the duration of the clinical trial and the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, or post-ovulation methods) and withdrawal are not
acceptable methods of contraception.
9. For women of childbearing potential: agreement to remain abstinent (refrain
from heterosexual intercourse) or use non-hormonal contraceptive methods
that result in a failure rate of < 1% per year during the treatment period and
for at least 28 days after the last dose of study drug.
a. A woman is considered to be of childbearing potential if she is
post-menarcheal, has not reached a post-menopausal state (≥ 12
continuous months of amenorrhea with no identified cause other than
menopause), and has not undergone surgical sterilization (removal of
ovaries and/or uterus).
b. Examples of non-hormonal contraceptive methods with a failure rate of
< 1% per year include bilateral tubal ligation, male sterilization, and
copper intrauterine devices.
c. The reliability of sexual abstinence should be evaluated in relation to
the duration of the clinical trial and the preferred and usual lifestyle of
the patient. Periodic abstinence (e.g., calendar, ovulation,
symptothermal, or post-ovulation methods) and withdrawal are not
acceptable methods of contraception
10.Informed of, willing and able to comply with all of the protocol requirements
and the investigational nature of the study, and have signed an informed
consent form (ICF) in accordance with institutional and regulatory requirements.

1. Pregnant (positive pregnancy test) or lactating women, and male subjects
with partners who are pregnant or lactating
2. History or other evidence of bleeding from esophageal varices.
3. Evidence of liver cirrhosis or decompensated liver disease such as ascites,
esophageal or gastric varices, splenomegaly, nodular liver, jaundice, hepatic encephalopathy.
4. One or more of the following laboratory abnormalities at screening:
a. Total serum bilirubin > 2.5 mg/dL ( > 42.75 μmol/L). For patients with
documented Gilbert’s syndrome total bilirubin > 2.75 mg/dL ( > 47 μmol/L).
b. International normalized ratio (INR) > 1.5.
c. Serum albumin < 3.0 g/dL ( < 30 g/L).
d. Platelet count < 140,000 cells/mm3.
5. 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, etc.).
6. Documented history or other evidence of metabolic liver disease within one
year of randomization.
7. Positive test for hepatitis A (IgM anti-HAV), hepatitis C, hepatitis D, or human
immunodeficiency virus.
8. 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 or
oral therapy for HSV I or HSV II.
9. History of or suspicion of hepatocellular carcinoma or alphafetoprotein ≥ ULN at screening.
10.History of significant gastrointestinal disease (including but not limited to gastric ulcers).
11.History of clinically significant cardiovascular, endocrine, renal, ocular,
pulmonary, psychiatric or neurological disease.
12.Evidence of an active or suspected cancer or a history of malignancy other
than adequately treated basal cell carcinoma.
13.History of organ transplantation.
14.Previous or concurrent HBV treatments in the past 6 months.
15.History of capsid modulators treatment, including treatment in investigative trials
16.Participation in an investigational drug or device study within 30 days prior to randomization.
17.Taking any drugs or nutrients that are prohibited medications and prohibited
food defined in this study.
18.Significant acute infection (e.g., influenza, local infection) or any other
clinically significant illness within 2 weeks of randomization.
19.Clinically relevant ECG abnormalities on screening ECG.
20.Abnormal renal function including serum or plasma creatinine > ULN or
calculated creatinine clearance < 70 mL/min using the Cockcroft Gault formula.
21.Donation or loss of blood over 500 mL within 3 months prior to randomization.
22.Administration of any blood product within 3 months prior to randomization.
23.History of alcohol abuse (consumption of more than 2 standard drinks per
day on average; 1 standard drink = 10 grams of alcohol) and/or drug abuse
within one year of randomization; positive test result for drugs of abuse or
alcohol breath test at screening.
24.Subjects under judicial supervision, guardianship or curatorship.
25.Medical or social conditions that would potentially interfere with the
subject’s ability to comply with the study visit schedule or the study assessments.