A Study in Healthy Volunteers and in Participants With Chronic Hepatitis B to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7020531
Condition: Hepatitis B, Chronic
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Intervention: Placebo; RO7020531
Intervention description: Placebo matching to RO7020531 will be administered as per schedule specified in the respective arm.; RO7020531 will be administered as per schedule specified in the respective arm.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 160.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This sponsor-open, investigator- and participant-blinded, multi-center study will assess the
      safety, tolerability, pharmacokinetics and pharmacodynamics of RO7020531 in healthy
      participants and in participants with chronic hepatitis B. Part I will be conducted in two
      portions: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) which will include
      only healthy volunteers. Part II will commence after completion of the MAD portion of Part I
      and will include only Chronic Hepatitis B (CHB) participants.
    

Eligibility criteria:

        Inclusion Criteria:

        Part 1: SAD and MAD in Healthy Volunteers

          -  Non-smokers, or use of less than (<) 10 cigarettes (or equivalent nicotine-containing
             product) per day

          -  Negative Anti-Nuclear Antibody (ANA) test; or positive with dilutions not greater than
             1:40 and with no associated history or symptoms of potential connective tissue disease
             or other immune-mediated diseases

        Part 2: CHB Participants

          -  CHB infection (positive test for Hepatitis B surface antigen [HBsAg] for more than 6
             months prior to randomization)

          -  For Cohort 1, 2, 3 and 4: HBsAg detectable at screening

          -  For Cohort 1, 2 and 3: Hepatitis B virus deoxyribose nuclic acid (HBV DNA) < 90
             international unit per milliliter (IU/mL) for at least 6 months prior to
             randomization; HBV DNA < 90 IU/mL at screening by Roche Cobas assay

          -  For Cohort 4: HBV DNA at screening >= 2 × 10*4 IU/mL for HBeAg positive and >= 2 x
             10*3 IU/mL for hepatitis B e antigen (HBeAg) negative participants

          -  For Cohort 1, 2 and 3: Alanine amino transferase (ALT) =<1.5 × upper limit of normal
             (ULN) during the 6 months prior to randomization confirmed by two measurements
             separated by at least 14 days; ALT at screening =< 1.5 × ULN.

          -  For Cohort 4: ALT and aspartate aminotransferase (AST) at screening and Day -1 visit:
             =< 5 × ULN.

          -  Negative ANA test; or positive with dilutions not greater than 1:40 and with no
             associated history or symptoms of potential connective tissue disease or other
             immune-mediated diseases

          -  Liver biopsy, Fibroscan® or equivalent elastography test obtained within 6 months
             prior to randomization demonstrating liver disease consistent with chronic HBV
             infection with absence of cirrhosis and absence of extensive bridging fibrosis
             (cirrhosis or extensive bridging fibrosis are defined as greater than or equal to
             (>/=) Metavir 3, recommended cut-off for Fibroscan 8.5 kilopascals [kPa])

          -  For Cohort 1, 2 and 3: On treatment with tenofovir, entecavir, adefovir, or
             telbivudine, either as single agents or in combination, for at least 6 months

          -  For Cohort 4: Hepatitis B virus (HBV) treatment naïve or not on any anti-HBV treatment
             for the past 6 months

        Exclusion Criteria:

        Part 1: SAD and MAD in Healthy Volunteers

          -  History of immunologically mediated disease (e.g., inflammatory bowel disease,
             idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic
             anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or
             any other autoimmune disease); clinically significant psychiatric disease, acute
             infection (e.g., influenza), gastrointestinal (GI) disease (including inflammatory
             bowel disease, peptic ulcer disease, GI hemorrhage)

          -  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 pegylated interferon [PEG-IFN]) within the 8 weeks
             prior to the first dose of study drug or the expectation that such treatment will be
             needed at any time during the study

          -  Any clinically significant concomitant disease or condition that could interfere with,
             or for which the treatment of 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 Hepatitis A virus antibody (HAV Ab IgM), HBsAg, Hepatitis C antibody (HCV
             Ab), or positive for human immunodeficiency virus (HIV) at screening

          -  History of clinically significant thyroid disease; also, participants with clinically
             significant elevated thyroid-stimulating hormone (TSH) concentrations at screening

          -  Positive results for anti-mitochondrial antibody (AMA), anti-smooth muscle antibody
             (ASMA) or thyroid peroxidase antibody

        Part 2: CHB Participants

          -  History of liver cirrhosis

          -  History or other evidence of bleeding from esophageal varices

          -  Decompensated liver disease (e.g., Child-Pugh Class B or C clinical classification or
             clinical evidence such as ascites or varices)

          -  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 steato-hepatitis, etc.). A clinical
             diagnosis of fatty liver is allowed provided that non alcoholic steatohepatitis (NASH)
             has been excluded by liver biopsy.

          -  Documented history or other evidence of metabolic liver disease within one year of
             randomization

          -  Positive test for Hepatitis A virus (IgM anti-HAV), Hepatitis C virus (HCV), Hepatitis
             D virus, Hepatitis E virus (HEV), or human immunodeficiency virus (HIV).

          -  History of or suspicion of hepatocellular carcinoma or alpha fetoprotein >/=13
             nanograms per milliliter (ng/mL) at screening

          -  History of immunologically mediated disease (e.g., inflammatory bowel disease,
             idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic
             anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or
             any other autoimmune disease); clinically significant psychiatric disease; acute
             infection (e.g., influenza); GI disease (including inflammatory bowel disease, peptic
             ulcer disease, GI hemorrhage, or history of pancreatitis); clinically significant
             cardiovascular (including postural hypotension), endocrine, renal, ocular, pulmonary
             or neurological disease.

          -  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 drug or the expectation that such treatment will be needed at any time during
             the study

          -  Cohort 4: Concurrent HBV treatments

          -  History of organ transplantation

          -  Clinically significant thyroid disease; also, participants with clinically significant
             elevated TSH concentrations at screening

          -  Positive results for AMA, ASMA or thyroid peroxidase antibody