A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7049389 in Healthy Volunteers and Chronic Hepatitis B Virus (HBV) Infected Participants

Inclusion criteria

Part 1- Healthy Volunteers only:

• 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 Electrocardiogram (ECG), hematology, blood chemistry, serology and urinalysis
• A Body Mass Index (BMI) between 18 to 30 kilograms per square meter (kg/m^2) inclusive
• Female participants must be either surgically sterile or post-menopausal for at least one year
• For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Part 2- Chronic HBV-infected participants only:

• A BMI between 18 to 30 kg/m^2 inclusive
• Chronic Hepatitis B infection, defined as positive test for Hepatitis B surface antigen (HBsAg) for more than 6 months prior to randomization
• HBV DNA at screening greater than or equal to (>/=) 2 × 10^4 international units per milliliter (IU/mL) for Hepatitis B e antigen (HBeAg) positive participants, or >/=2 × 10^3 IU/mL for HBeAg-negative participants
• 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
• For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm
• For women of childbearing potential: agreement to remain abstinent or use non-hormonal contraceptive methods that result in a failure rate of less than (<)1 percent (%) per year during the treatment period and for at least 3 months after the last dose of study drug

Part 3- Chronic HBV Participants Only:

• A BMI between 18 to 32 kg/m^2 inclusive
• Chronic hepatitis B infection, defined as positive test for HBsAg or HBV DNA, or positive HBeAg, for more than 6 months prior to screening
• For Cohorts only enrolling NUC-suppressed CHB participants (e.g. POM Cohort A), participants must have been treated with a single NUC (entecavir, tenofovir alafenamide, or tenofovir disoproxil fumarate) for at least 12 months. Participants must be on the same NUC therapy for at least 3 months prior to screening
• For Cohorts only enrolling anti-HBV treatment-naive and immune-active participants (e.g. POM Cohort B and Cohort C), previous anti-HBV treatments <30 days in total, and did not receive any anti-HBV treatments within 3 months prior to the first study dose
• 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
• For men: agreement to remain abstinent or use contraceptive measures, and agree to refrain from donating sperm
• For women of childbearing potential: agreement to remain abstinent or to use two approved contraceptive methods during the study and for at least 6 months after the last dose of study drug

Exclusion criteria

Part 1- Healthy Volunteers only:

• History or symptoms of any clinically significant gastrointestinal, renal, hepatic, broncho-pulmonary, neurological, psychiatric, cardio-vascular, endocrinological, hematological or allergic disease, metabolic disorder, cancer or cirrhosis
• History of Gilbert's syndrome
• Participants who have had significant acute infection, e.g., influenza, local infection, acute gastrointestinal symptoms or any other clinically significant illness within two weeks of dose administration
• Any confirmed significant allergic reactions (urticaria or anaphylaxis) against any drug, or multiple drug allergies
• Any clinically significant concomitant diseases 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
• Positive test at screening of any of the following: Hepatitis A (HAV IgM Ab), Hepatitis B (HBsAg), Hepatitis C (HCV RNA or HCV Ab) or human immunodeficiency virus (HIV Ab)
• Acute narrow-angle glaucoma (for MAD-midazolam cohorts)

Part 2- Chronic HBV-infected participants only:

• History or other evidence of bleeding from esophageal varices
• Evidence of liver cirrhosis or decompensated liver disease such as ascites, esophageal or gastric varices, splenomegaly, nodular liver, jaundice, hepatic encephalopathy
• 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.)
• Documented history or other evidence of metabolic liver disease within one year of randomization
• Positive test for hepatitis A (IgM anti-HAV), hepatitis C, hepatitis D, or human immunodeficiency virus
• History of or suspicion of hepatocellular carcinoma or alphafetoprotein >/= Upper limit of normal (ULN) at screening
• History of clinically significant gastrointestinal, cardiovascular, endocrine, renal, ocular, pulmonary, psychiatric or neurological disease
• History of organ transplantation
• Previous or concurrent HBV treatments in the past 6 months
• Significant acute infection (e.g., influenza, local infection) or any other clinically significant illness within 2 weeks of randomization

Part 3- Chronic Hepatitis B Participants Only:

• History or other evidence of bleeding from esophageal varices
• Evidence of liver cirrhosis or decompensated liver disease such as ascites, esophageal or gastric varices, splenomegaly, nodular liver, jaundice, or hepatic encephalopathy
• 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 statohepatitis, etc.)
• History of thyroid disease poorly controlled on prescribed medications or clinically relevant abnormal thyroid function tests
• Documented history or other evidence of metabolic liver disease within one year of screening
• Positive test for hepatitis A (IgM anti-HAV), hepatitis C, hepatitis D, HEV, or HIV
• Diagnosed or suspected hepatocellular carcinoma
• History of clinically significant gastrointestinal, cardiovascular, endocrine, renal, ocular, pulmonary, psychiatric, or neurological disease
• History of organ transplantation
• Significant acute infection (e.g. influenza, local infection) or any other clinically significant illness within 2 weeks of screening