CHRONIC HEPATITIS B VIRUS INFECTION

The purpose of this test is to test the safety of different doses of RO7062931, and to explore the effects of RO7062931 on humans and diseases.

RO7062931 sterile liquid for inection

RO7062931

sterile liquid for injection

120 mgl1-mlvial

Primary Objective:
The primary objectives of this study are:
• To assess the safety and tolerability of RO7062931 compared to placebo after
single-ascending subcutaneous (SC) doses in healthy volunteers (HVs).
• To assess the safety and tolerability of RO7062931 compared to placebo after multiple SC doses in chronic Hepatitis B (CHB) patients.
Secondary Objectives
The secondary objectives for this study are as follows:
For Part 2:(Taiwan only participated in the second part of the trial)
• To assess the plasma and urine PK of RO7062931 and if applicable metabolite(s), after multiple SC doses.
• To study HBsAg dynamics after SC administration of RO7062931.
Exploratory Objectives
The exploratory objectives of this study are as follows:
Pharmacodynamics (PD) exploratory objectives:
For Part 2: to explore the effect of multiple doses of RO7062931 on viral and anti-viral
parameters other than quantitative HBsAg during and after the end of treatment in CHB patients.
o explore the effects of RO7062931 doses on further exploratory biomarkers.

Inclusion criteria:
Study subjects must meet the below criteria for study entry.
Part 1 - Healthy volunteers only:
1. Able to participate and willing to give written informed consent and to comply with the study restrictions.
2. Healthy male and female (of non-childbearing potential) subjects. Health status is defined by
absence 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.
3. 18 to 65 years of age, inclusive.
4. A Body Mass Index (BMI) between 18 to 30 kg/m2 inclusive and a body weight of at least 50 kg.
5. Women should be of non-childbearing potential. A woman is considered to be of childbearing
potential if she is post-menarcheal but has not reached a post-menopausal state
(≥ 12 continuous months of amenorrhea with no identified cause other than menopause,
confirmed by follicle-stimulating hormone [FSH], or amenorrhea for at least 24 months if on
hormone replacement therapy), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
All males must agree to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agree to refrain from donating sperm, as defined below:
With female partners of childbearing potential or pregnant female partners, men must
remain abstinent or use a condom during the treatment period and up to 105 days after
the last dose to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
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 healthy volunteer. Periodic
abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and
withdrawal are not acceptable methods of contraception.
6. Non-smoker (nor tobacco containing products) for at least 90 days prior to dosing on Day 1
and agree to remain as non-smoker during the study.
Parts 2 - CHB patients only:
1. Ability and willingness of patient to provide written informed consent.
2. Adult male and female (of non-childbearing potential) patients, aged 18-65 years (inclusive).
3. A BMI between 18 to 32 kg/m2 inclusive.
4. Chronic hepatitis B infection.
5. Positive test for HBsAg for more than 6 months prior to randomization.
6. HBsAg titer ≥ 103 IU/mL at screening.
7. On entecavir, tenofovir, adefovir or telbivudine treatment for at least 6 months prior to
randomization and will remain on stable treatment during the study.
8. HBV DNA ≤ 90 IU/mL for at least the preceding 6 months.
9. Screening laboratory values (hematology, chemistry, urinalysis) obtained up to 56 days prior
to first study treatment within normal ranges, with the exception of otherwise specified criteria
or judged to be not clinically significant by Principal Investigator (PI) and Medical Monitor.
10. Alanine transaminase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase
(GGT), and alkaline phosphatase (ALP) at screening ≤ 1.5 × upper limit of normal (ULN);
normal values for total bilirubin and prothrombin time (PT)/International Normalized Ratio
(INR)/activated partial thromboplastin time (aPTT) tests at screening (except for patients with
Gilbert’s syndrome TB ≤ 47 µmol/L [2.75 mg/dL]).
11. 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 3, recommended cut-off for Fibroscan 8.5 kPa).
12. Women should be of non-childbearing potential. A woman is considered to be of childbearing
potential if she is post-menarcheal but has not reached a post-menopausal state
( ≥ 12 continuous months of amenorrhea with no identified cause other than menopause,
confirmed by FSH, or amenorrhea for at least 24 months if on hormone replacement
therapy), and has not undergone surgical sterilization (removal of ovaries and/or uterus).
All males must agree to remain abstinent (refrain from heterosexual intercourse) or use
contraceptive measures, and agreement to refrain from donating sperm, as defined below:
With female partners of childbearing potential or pregnant female partners, men must
remain abstinent or use a condom during the treatment period and up to 105 days after
the last dose to avoid exposing the embryo. Men must refrain from donating sperm during this same period.
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.

1. Women who are lactating.
2. Any suspicion or history of alcohol and/or other substance abuse or dependence in the past 6 months.
3. Positive urine drug and alcohol screen (barbiturates, benzodiazepines, methadone,
amphetamines, methamphetamines, opiates, cocaine, cannabinoids and alcohol), or positive
cotinine test at screening or Day − 1.
4. Positive result on hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV) 1 and 2.
5. Confirmed (e.g., two consecutive triplicate measurements) average systolic blood pressure
(SBP) > 140 or < 90 mmHg, and diastolic blood pressure (DBP) > 90 or < 45 mmHg at Screening.
6. Confirmed (e.g., two consecutive triplicate measurements) average resting pulse rate
(PR) > 90 or < 45 beats per minute (bpm) at Screening.
7. A personal history of unexplained blackouts or faints, or known risk factors for Torsade de
Pointes (e.g., hypokalemia, heart failure). Clinically significant abnormal ECG, including
arrhythmias or marked QT abnormalities (QTcF < 300 msec or > 450 msec at Screening).
8. ECG morphology at screening that renders measurement of QT interval imprecise (e.g.,
neuromuscular artifact that cannot be readily eliminated, indistinct QRS onset, low amplitude
T-wave, merged T- and U-waves, prominent U-waves, arrhythmias, etc.).
9. Screening or baseline ECG evidence of atrial fibrillation, atrial flutter, complete right or left
bundle branch block, Wolff-Parkinson-White syndrome, or cardiac pacemaker.
10. Personal or family history of congenital long QT syndrome or sudden death.
11. Any out of range findings in liver function tests, INR and renal function tests or any
clinically significant abnormalities (as judged by the Investigator) in the physical examination
and in the remaining laboratory test results (including hepatic and renal panels, complete
blood count, chemistry panel and urinalysis) at screening and on Day-1.
12. Participation in an investigational drug or device study within 90 days prior to screening or
5 times the half-life of the investigational drug (whichever is longer).
13. Donation of blood over 500 mL within three months prior to screening.
14. Concomitant disease or condition (including allergic reactions against any drug, or multiple
allergies) 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
healthy volunteers in this study.
15. Any major illness within the one month preceding the Screening visit, or any febrile illness
within the two weeks preceding the screening visit.
16. Alcohol consumption of more than 2 standard drinks per day on average; 1 standard drink
equals 10 grams of alcohol (for further guidance please see Appendix 9).
17. Hypersensitivity to the excipients of the study drug.
CHB patients only:
1. Women who are lactating.
2. History or other evidence of bleeding from esophageal varices.
3. Decompensated liver disease (e.g., Child-Pugh Class B or C clinical classification [see
Appendix 10] or clinical evidence such as ascites or varices).
4. 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, non-alcoholic steatohepatitis, etc.).
5. Documented history or other evidence of metabolic liver disease within one year of randomization.
6. Positive test for hepatitis A (IgM anti-HAV), hepatitis C, or HIV.
7. Documented history of infection with hepatitis D 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 of oral/topical therapy for Herpes simplex virus (HSV) I or HSV II.
9. History of or suspicion of hepatocellular carcinoma or alpha fetoprotein (AFP) ≥ 13 ng/mL at Screening.
10. 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).
11. History of clinically significant and not adequately controlled cardiovascular, endocrine,
gastrointestinal, renal, ocular, pulmonary, 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 having received (in the last 6 months) or currently receiving any systemic antineoplastic (including radiation) or immune-modulatory treatment (including systemic corticosteroids).
14. History of organ transplantation.
15. Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or
multiple drug allergies (non-active hay fever is acceptable).
16. Significant acute infection (e.g., influenza, local infection) or any other clinically significant
illness within 2 weeks of randomization.
17. Clinically relevant ECG abnormalities on screening ECG including arrhythmias or marked QT
abnormalities (QTcF < 300 msec or > 450 msec) at Screening.
18. Any of the following laboratory parameters at screening:
a) White blood cells (WBC) < 3,000 cells/ mm3
b) Neutrophil count < 1500 cells/mm3
c) Platelet count < 140,000 cells/mm3
d) aPTT > 40 seconds, INR > 1.2
e) Hemoglobin (Hgb) < 12 g/dL in females or < 13 g/dL in males.
19. Abnormal renal function including serum creatinine > ULN or calculated creatinine
clearance < 70 mL/min (using the Cockcroft Gault formula).
20. Participation in an investigational drug or device study within 30 days prior to randomization.
21. Donation or loss of blood over 500 mL within 3 months prior to starting study medication.
22. Administration of any blood product within 3 months of randomization.
23. History or evidence of alcohol abuse (consumption of more than 2 standard drinks per day
on average; 1 standard drink equals 10 grams of alcohol, for further guidance please see
Appendix 9) and/or drug abuse within one year of randomization; positive test result for
drugs of abuse at Screening.
24. Patients under judicial supervision, guardianship or curatorship.
25. Medical or social conditions that would potentially interfere with the patient’s ability to comply
with the study visit schedule or the study assessments.