This study is a multicenter, three-part study. Parts 1 and 2 are randomized, investigator- and participant-blinded, placebo-control, single-ascending dose (SAD) and multiple-ascending dose (MAD) study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RO7049389 following oral administration in healthy volunteers and chronic HBV infected participants. Part 3 is a non-randomized, non-controlled, open-label part to assess the efficacy and safety of RO7049389 when administered in combination with standard-of-care therapies for up to 48 weeks in nucleos(t)ide (NUC)-suppressed and treatment-naive chronic hepatitis B (CHB) participants.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
192
Single dose of 100 mcg midazolam solution will be administered orally, before (Day -1) and after (Day 14) the treatment with RO7049389 or matching placebo
Placebo matching to RO7049389 will be administered as per schedule described in individual arm.
RO7049389 will be administered as per schedule described in individual arm.
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Royal Melbourne Hospital
Parkville, Victoria, Australia
Acibadem City Clinic Tokuda Hospital Ead
Sofia, Bulgaria
Nanfang Hospital, Southern Medical University
Guangzhou, China
Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)
Shanghai, China
Huashan Hospital Affiliated to Fudan University
Shanghai, China
The University of Hong Kong; Queen Mary Hospital
Hong Kong, Hong Kong
Prince of Wales Hospital
Shatin, New Territories, Hong Kong
Middlemore Hospital
Auckland, New Zealand
Auckland Clinical Studies Limited
Grafton, New Zealand
...and 11 more locations
Part 1: Percentage of Participants With Adverse Events
Time frame: Up to Day 29 (Part 1a), Day 44 (Part 1b), Day 42 (Part 1c)
Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389
Time frame: Up to 28 days
Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389
Time frame: Up to 28 days
Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389
Time frame: Up to 28 days
Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389
Time frame: Up to 28 days
Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389
Time frame: Up to Day 28
Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389
Time frame: Up to Day 28
Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389
Time frame: Up to Day 28
Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389
Time frame: Up to Day 28
Part 2: Percentage of Participants With Adverse Events
Time frame: Up to Day 112
Part 2: Quantitative Plasma HBV DNA Level
Time frame: Baseline - Day 112
Part 3: Proportion of Patients Achieving Functional Cure
Functional cure is defined as HBV DNA \< lower limit of quantification (LLOQ, 20 IU/mL) with HBsAg loss (\< 0.05 IU/mL) at 24 weeks post-treatment.
Time frame: Every 2-4 weeks from Baseline through Week 72
Part 1b: Food Effect on Cmax of RO7049389
This outcome measure evaluated the effect of food on the pharmacokinetics (PK) of RO7049389 after the administration of a single dose. Participants were fed a high-fat, high-calorie breakfast (per FDA food effect bioavailability and bioequivalence study recommendations) 30 minutes prior to dosing after fasting overnight for at least 8 hours. ANOVA (factors fasted/fed state and subject) was performed for measurements available in subjects in both fasted and fed states.
Time frame: Day 16
Part 1b: Food Effect on AUCinf of RO7049389
This outcome measure evaluated the effect of food on the pharmacokinetics (PK) of RO7049389 after the administration of a single dose. Participants were fed a high-fat, high-calorie breakfast (per FDA food effect bioavailability and bioequivalence study recommendations) 30 minutes prior to dosing after fasting overnight for at least 8 hours. ANOVA (factors fasted/fed state and subject) was performed for measurements available in subjects in both fasted and fed states.
Time frame: Day 16
Part 1c: Cmax of Midazolam
This endpoint presents the geometric mean ratio (after RO7049389/before RO7049389).
Time frame: Up to Day 14
Part 1c: AUCinf of Midazolam
This endpoint presents the geometric mean ratio (after RO7049389/before RO7049389).
Time frame: Up to Day 14
Part 1c: Tmax of RO7049389
Time frame: Up to Day 14
Part 1c: Cmax of RO7049389
Time frame: Up to Day 14
Part 1c: AUC0-12hr of RO7049389
Time frame: Up to Day 14
Part 1c: CLr of RO7049389
Time frame: Up to Day 14
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Part 1c: Accumulation Ratio of RO7049389
This endpoint presents the geometric mean ratio of AUC after a single dose (Day 1) and AUC after having received multiple doses (Day 14) within each arm.
Time frame: Day 1, Day 14
Part 1c: T1/2 of RO7049389
Time frame: Up to Day 14
Part 1c: Ae of RO7049389
Time frame: Up to Day 14
Part 1c: Ctrough of RO7049389
Time frame: Up to Day 14
Part 2: HBV DNA < Lower Limit of Quantification (LLOQ)
Time frame: Baseline - Day 112/Follow-up Day 84
Part 2: Tmax of RO7049389
Time frame: Up to Day 28
Part 2: Cmax of RO7049389
Time frame: Up to Day 28
Part 2: AUCtau of RO7049389
Time frame: Up to Day 28
Part 2: Accumulation Ratio of RO7049389
This endpoint presents the geometric mean ratio of AUC after a single dose (Day 1) and AUC after having received multiple doses (Day 28) within each arm.
Time frame: Day 1, Day 28
Part 2: T1/2 of RO7049389
Time frame: Up to Day 28
Part 2: Ctrough of RO7049389
Time frame: Up to Day 28
Part 3: Percentage of Participants With AEs
Time frame: 72 weeks
Part 3: Hepatitis B Surface Antigen (HBsAg) Level
Time frame: Baseline - Week 72
Part 3: Hepatitis B e-Antigen (HBeAg) Levels
Time frame: Baseline - Week 72
Part 3: HBV RNA Level
Time frame: Baseline - Week 72
Part 3: HBV Core-Related Antigen (HBcrAg) Levels
Time frame: Baseline - Week 72
Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation
Time frame: Week 12 - Week 72
Part 3: Percentage of Participants With Anti-Hepatitis B Core Antigen (HBc) Antibodies
Time frame: Up to Week 72
Part 3: HBV DNA Level
Time frame: Baseline - Week 72
Part 3: HBV DNA < Lower Limit of Quantification (LLOQ)
Time frame: Baseline - Week 72
Part 3: Tmax of RO7049389
Time frame: Day 1 - Week 48
Part 3: Cmax of RO7049389
Time frame: Day 1 - Week 48
Part 3: AUCtau of RO7049389
Time frame: Day 1 - Week 48
Part 3: T1/2 of RO7049389
Time frame: Day 1 - Week 48