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RO7049389, a hepatitis B virus (HBV) core protein allosteric modulator being developed for the treatment of chronic HBV infection, was found to be safe and well tolerated in healthy participants (part 1 of this study). The objective of this proof-of-mechanism study (part 2) was to evaluate the safety, pharmacokinetics, and antiviral activity of RO7049389 in patients with chronic HBV infection.

Background In China, the clinical management of chronic hepatitis B (CHB) is complicated by the use of various-nucleoside/nucleotide analogue (NUC) regimens in treatment-naive patients, including NUCs with low genetic barriers to resistance, with/without add-on therapy and de novoNUC combinations. This longitudinal observational study therefore investigated the real-world clinical management and efficacy of NUC therapy in treatment-naive CHB patients in China.Methods Treatment-naive CHB patients initiated on NUC therapy were enrolled from 63 hospitals in tier-2 Chinese cities. Demographic and treatment-specific data were collected, with the objective of reporting real-world treatment patterns and comparing the effectiveness of entecavir (ETV) treatment and lamivudine (LAM)-based treatment. We herein report the first-year data.Results 3,408 NUC-naive patients were enrolled and treated with NUCs (53% ETV, 18% LAM-based, 29% other). Overall, 6.6% of patients modified their initial treatment, with ETV having lower rates of treatment modification than other major NUCs (P<0.05). At week 52, the virological response rate was higher with ETV than with LAM-based treatment (77.0% versus 61.4%; P<0.0001). LAM-based treatment was associated with a higher probability of virological breakthrough and genotypic resistance (21.4% and 19.6%, respectively) than ETV (1.6% and 0.1%, respectively; P<0.0001). Treatment-related adverse events or serious adverse events were uncommon.Conclusions In this nationwide observational study, more than 50% of patients with CHB in tier-2 city hospitals in China initially received ETV therapy. Consistent with clinical trial results, ETV was more effective than LAM-based treatments in a real-world setting, with the rate of treatment modification being relatively low in ETV-treated patients. ClinicalTrials.gov Identifer: NCT01726439.

RO7049389, an inhibitor of hepatitis B virus (HBV) capsid assembly, is being developed for the treatment of patients with chronic HBV infection. The objectives of this first-in-human study are to assess the safety, tolerability, pharmacokinetics (PK), food effect, inhibitory effect on CYP3A, and effect on QT of RO7049389 in healthy participants. Five components, single-ascending-dose (SAD) cohorts, multiple-ascending-dose (MAD) cohorts, food effect assessment, drug-drug interaction assessment, and concentration-QT analysis were integrated in one study (five-in-one).