Hepatitis B Virus Infection

This study is designed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending doses in healthy volunteers (HV) and participants diagnosed with chronic hepatitis B (CHB).

RO7239958

RO7239958

Solution for injection

100 mg/mL

Primary Outcome Measures :
1.Number of Participants With Adverse Events (AEs)
2.Number of Participants With Clinically Significant Changes in Vital Signs
3.Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings
4.Number of Participants With Clinically Significant Changes in Clinical Laboratory Results
5.Number of Participants With Injection Site Reactions (ISRs)

Secondary Outcome Measures :
1.Maximum Plasma Concentration (Cmax) of RO7239958
2.Time to Cmax (Tmax) of RO7239958
3.Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958
4.Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958
5.Half-life (t1/2) of RO7239958
6.Cumulative Amount of Drug Excreted in Urine (Ae)
7.Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels
8.Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels
9.Part 2a: Number of Participants With HBsAg Loss
10.Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants
11.Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants
12.Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification

All Parts:
-Female participants should be of non-childbearing potential and male participants who are with pregnant partners or partners of childbearing potential must agree to remain abstinent or use contraceptive measures

Part 1 (SAD HV only)
1.Healthy, as judged by the Investigator
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)
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 drug in the 3 months prior to randomisation
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
6.No past or current diagnosis of cirrhosis

All Parts:
1.History or presence of significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological 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 of lymphoma, leukemia, or malignancy within the past five years
3.Positive for human immunodeficiency virus (HIV) infection
4.Participant under judicial supervision, guardianship or curatorship

Part 1 (SAD HV only):
1.Screening ECG showing clinically relevant abnormalities
2.Abnormal blood pressure
3.History or presence of liver disease, or known hepatic or biliary abnormalities
4.Alanine aminotransferase (ALT) ≥1.5 × upper limit of normal (ULN)
5.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
6.Positive for hepatitis B surface antigen (HBsAg), or hepatitis B core total antibody [anti-HBc]), or hepatitis C virus (HCV) antibody test result

Part 2 (CHB only):
1.History or presence of bridging fibrosis or cirrhosis or decompensated liver disease
2.History or presence of a medical condition associated with liver disease other than HBV infection. Other known hepatic or biliary abnormalities
3.History of or suspicion of hepatocellular carcinoma or alpha fetoprotein (AFP) ≥13 ng/mL
4.History of having received (in the last six months) or currently receiving any systemic antineoplastic (including radiation) or immune-modulatory treatment (including systemic corticosteroids)
5.History of organ transplantation
6.Estimated glomerular filtration rate (eGFR) <70 mL/min/1.73m^2
7.Confirmed QT interval corrected using Fridericia's formula (QTcF) >450 ms
8.Expected to need any other systemic antiviral therapy at any time during participation in the study
9.Positive hepatitis C antibody test