Hepatitis B, Chronic
Conditions
Brief summary
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.
Interventions
DRUGMidazolam
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
OTHERPlacebo
Placebo matching to RO7049389 will be administered as per schedule described in individual arm.
DRUGRO7049389
RO7049389 will be administered as per schedule described in individual arm.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Percentage of Participants With Adverse Events | 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 | Up to 28 days | — |
| Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389 | Up to 28 days | — |
| Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389 | 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 | Up to 28 days | — |
| Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389 | Up to Day 28 | — |
| Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389 | Up to Day 28 | — |
| Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389 | Up to Day 28 | — |
| Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389 | Up to Day 28 | — |
| Part 2: Percentage of Participants With Adverse Events | Up to Day 112 | — |
| Part 2: Quantitative Plasma HBV DNA Level | Baseline - Day 112 | — |
| Part 3: Proportion of Patients Achieving Functional Cure | Every 2-4 weeks from Baseline through Week 72 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Baseline - Day 112/Follow-up Day 84 | — |
| Part 2: Tmax of RO7049389 | Up to Day 28 | — |
| Part 2: Cmax of RO7049389 | Up to Day 28 | — |
| Part 2: AUCtau of RO7049389 | Up to Day 28 | — |
| Part 2: Accumulation Ratio of RO7049389 | Day 1, Day 28 | 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. |
| Part 2: T1/2 of RO7049389 | Up to Day 28 | — |
| Part 2: Ctrough of RO7049389 | Up to Day 28 | — |
| Part 3: Percentage of Participants With AEs | 72 weeks | — |
| Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Baseline - Week 72 | — |
| Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Baseline - Week 72 | — |
| Part 3: HBV RNA Level | Baseline - Week 72 | — |
| Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Baseline - Week 72 | — |
| Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 12 - Week 72 | — |
| Part 3: Percentage of Participants With Anti-Hepatitis B Core Antigen (HBc) Antibodies | Up to Week 72 | — |
| Part 3: HBV DNA Level | Baseline - Week 72 | — |
| Part 1b: Food Effect on Cmax of RO7049389 | Day 16 | 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. |
| Part 3: Tmax of RO7049389 | Day 1 - Week 48 | — |
| Part 3: Cmax of RO7049389 | Day 1 - Week 48 | — |
| Part 3: AUCtau of RO7049389 | Day 1 - Week 48 | — |
| Part 3: T1/2 of RO7049389 | Day 1 - Week 48 | — |
| Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Baseline - Week 72 | — |
| Part 1b: Food Effect on AUCinf of RO7049389 | Day 16 | 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. |
| Part 1c: Cmax of Midazolam | Up to Day 14 | This endpoint presents the geometric mean ratio (after RO7049389/before RO7049389). |
| Part 1c: AUCinf of Midazolam | Up to Day 14 | This endpoint presents the geometric mean ratio (after RO7049389/before RO7049389). |
| Part 1c: Tmax of RO7049389 | Up to Day 14 | — |
| Part 1c: Cmax of RO7049389 | Up to Day 14 | — |
| Part 1c: AUC0-12hr of RO7049389 | Up to Day 14 | — |
| Part 1c: CLr of RO7049389 | Up to Day 14 | — |
| Part 1c: Accumulation Ratio of RO7049389 | Day 1, Day 14 | 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. |
| Part 1c: T1/2 of RO7049389 | Up to Day 14 | — |
| Part 1c: Ae of RO7049389 | Up to Day 14 | — |
| Part 1c: Ctrough of RO7049389 | Up to Day 14 | — |
Countries
Australia, Bulgaria, China, Hong Kong, New Zealand, Singapore, Taiwan, Thailand
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo Healthy volunteers (HVs) received a single dose of placebo under fasted (Part 1a) or fed (Part 1b) conditions. | 11 |
| Part 1c: Multiple Ascending Dose (MAD) Placebo HVs received placebo either once-daily (QD) or twice-daily (BID) for 13 days, followed by a single dose on Day 14. | 10 |
| Part 2: Proof-of-Mechanism (POM) Placebo Participants with chronic hepatitis B virus (CHB) infection received placebo once daily (QD) or twice daily (BID) for 27 days, followed by a single dose on Day 28. | 6 |
| Part 1a: SAD Cohort 1 HVs received a single dose of 150 mg of RO7049389 under fasted conditions. | 3 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) Part 1a: Single oral dose of 450 mg of RO7049389 under fasted conditions. Part 1b: Single oral dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal. | 6 |
| Part 1a: SAD Cohort 3 HVs received a single dose of 1000 mg of RO7049389 under fasted conditions. | 3 |
| Part 1a: SAD Cohort 4 HVs received a single dose of 2000 mg of RO7049389 under fasted conditions. | 6 |
| Part 1a: SAD Cohort 5 HVs received a single dose of 1000 mg of RO7049389 under fasted conditions. | 6 |
| Part 1a: SAD Cohort 6 HVs received a single dose of 2500 mg of RO7049389 under fasted conditions. | 6 |
| Part 1c: MAD Cohort 1 HVs received 200 mg of RO7049389 BID under fasted conditions for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14. | 6 |
| Part 1c: MAD Cohort 2 HVs received 200 mg of RO7049389 BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14. | 7 |
| Part 1c: MAD Cohort 3 HVs received 400 mg of RO7049389 BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14. | 7 |
| Part 1c: MAD Cohort 4 HVs received 800 mg of RO7049389 BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14. | 6 |
| Part 1c: MAD Cohort 5 HVs received 600 mg of RO7049389 BID after a standard US FDA-recommended high-fat high-calorie meal for 13 days, followed by a single dose on Day 14. Participants also received a single oral dose of midazolam on Day -1 and Day 14. | 6 |
| Part 2: POM Cohort 1 Participants with CHB received 200 mg of RO7049389 BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28. | 6 |
| Part 2: POM Cohort 2 Participants with CHB received 400 mg of RO7049389 BID for 27 days after a standard US FDA recommended high-fat high-calorie meal, followed by a single dose on Day 28. | 6 |
| Part 2: POM Cohort 3 Participants with CHB received 600 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28. | 6 |
| Part 2: POM Cohort 4 Participants with CHB received 1000 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28. | 7 |
| Part 2: POM Cohort 5 Participants with CHB received 200 mg of RO7049389 QD for 27 days under fasted conditions, followed by a single dose on Day 28. | 6 |
| Part 3: Cohort A Nucleos(t)ide (NUC)-suppressed CHB participants received 600 mg of RO7049389 QD under fasted conditions in addition to an NUC (administered per local SoC) for 48 weeks. After the study treatment period, participants either continued NUC for another 24 weeks, or discontinued all treatment. | 32 |
| Part 3: Cohort B Treatment-naïve immune-active CHB participants 600 mg of RO7049389 QD under fasted conditions for 4 weeks, followed by RO7049389 + NUC (administered per local SoC) for an additional 44 weeks. After the study treatment period, participants either continued NUC for another 24 weeks, or discontinued all treatment. | 10 |
| Part 3: Cohort C Treatment-naïve immune-active CHB participants received 600 mg of RO7049389 QD under fasted conditions + NUC + pegylated interferon (Peg-IFN) for 48 weeks. After the study treatment period, participants either continued NUC for another 24 weeks, or discontinued all treatment. | 30 |
| Total | 192 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 | FG014 | FG015 | FG016 | FG017 | FG018 | FG019 | FG020 | FG021 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Noncompliance with study drug | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Participant refused to adhere to study protocol | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Participant unable to adhere to study visit schedule | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: Multiple Ascending Dose (MAD) Placebo | Part 2: Proof-of-Mechanism (POM) Placebo | Part 1a: SAD Cohort 1 | Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1a: SAD Cohort 3 | Part 1a: SAD Cohort 4 | Part 1a: SAD Cohort 5 | Part 1a: SAD Cohort 6 | Part 1c: MAD Cohort 1 | Part 1c: MAD Cohort 2 | Part 1c: MAD Cohort 3 | Part 1c: MAD Cohort 4 | Part 1c: MAD Cohort 5 | Part 2: POM Cohort 1 | Part 2: POM Cohort 2 | Part 2: POM Cohort 3 | Part 2: POM Cohort 4 | Part 2: POM Cohort 5 | Part 3: Cohort A | Part 3: Cohort B | Part 3: Cohort C | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 26.1 years STANDARD_DEVIATION 8.4 | 25.2 years STANDARD_DEVIATION 4.9 | 43.5 years STANDARD_DEVIATION 6.4 | 32.7 years STANDARD_DEVIATION 10.1 | 27.3 years STANDARD_DEVIATION 7.6 | 28.7 years STANDARD_DEVIATION 13.6 | 26.7 years STANDARD_DEVIATION 4.7 | 26.7 years STANDARD_DEVIATION 13.5 | 30.5 years STANDARD_DEVIATION 7 | 25.5 years STANDARD_DEVIATION 4.5 | 23.9 years STANDARD_DEVIATION 2.8 | 26.7 years STANDARD_DEVIATION 3.8 | 28.8 years STANDARD_DEVIATION 11.1 | 28.3 years STANDARD_DEVIATION 5.8 | 40.2 years STANDARD_DEVIATION 8.3 | 34.7 years STANDARD_DEVIATION 12.1 | 41.5 years STANDARD_DEVIATION 11.8 | 47.0 years STANDARD_DEVIATION 6.1 | 40.7 years STANDARD_DEVIATION 15.3 | 47.2 years STANDARD_DEVIATION 8.3 | 43.8 years STANDARD_DEVIATION 9.8 | 32.8 years STANDARD_DEVIATION 7.7 | 34.9 years STANDARD_DEVIATION 11.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 8 Participants | 6 Participants | 3 Participants | 6 Participants | 2 Participants | 6 Participants | 6 Participants | 4 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 5 Participants | 6 Participants | 6 Participants | 6 Participants | 7 Participants | 6 Participants | 30 Participants | 9 Participants | 30 Participants | 180 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 5 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 1 Participants | 5 Participants | 5 Participants | 5 Participants | 7 Participants | 5 Participants | 25 Participants | 5 Participants | 28 Participants | 102 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 9 Participants | 7 Participants | 0 Participants | 1 Participants | 5 Participants | 3 Participants | 6 Participants | 3 Participants | 6 Participants | 4 Participants | 7 Participants | 4 Participants | 3 Participants | 4 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 6 Participants | 4 Participants | 1 Participants | 76 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 2 Participants | 4 Participants | 1 Participants | 13 Participants | 5 Participants | 7 Participants | 40 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 3 Participants | 3 Participants | 6 Participants | 3 Participants | 6 Participants | 6 Participants | 6 Participants | 6 Participants | 7 Participants | 7 Participants | 6 Participants | 6 Participants | 5 Participants | 3 Participants | 4 Participants | 3 Participants | 5 Participants | 19 Participants | 5 Participants | 23 Participants | 152 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk | EG018 affected / at risk | EG019 affected / at risk | EG020 affected / at risk | EG021 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 0 / 32 | 1 / 10 | 0 / 30 |
| other Total, other adverse events | 3 / 11 | 6 / 10 | 3 / 6 | 1 / 3 | 3 / 6 | 3 / 3 | 5 / 6 | 2 / 6 | 3 / 6 | 5 / 6 | 4 / 7 | 2 / 7 | 1 / 6 | 1 / 6 | 4 / 6 | 4 / 6 | 5 / 6 | 4 / 7 | 2 / 6 | 22 / 32 | 9 / 10 | 30 / 30 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 | 1 / 6 | 0 / 3 | 0 / 6 | 0 / 3 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 6 | 0 / 7 | 0 / 6 | 1 / 32 | 1 / 10 | 2 / 30 |
Outcome results
Primary
Part 1: Percentage of Participants With Adverse Events
Time frame: Up to Day 29 (Part 1a), Day 44 (Part 1b), Day 42 (Part 1c)
Population: The safety analysis population included all participants who received at least one dose of study drug, whether prematurely withdrawn from the study or not.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1: Percentage of Participants With Adverse Events | 27.3 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 1: Percentage of Participants With Adverse Events | 33.3 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1: Percentage of Participants With Adverse Events | 50.0 Percentage of participants |
| Part 1a: SAD Cohort 3 | Part 1: Percentage of Participants With Adverse Events | 100 Percentage of participants |
| Part 1a: SAD Cohort 4 | Part 1: Percentage of Participants With Adverse Events | 83.3 Percentage of participants |
| Part 1a: SAD Cohort 5 | Part 1: Percentage of Participants With Adverse Events | 33.3 Percentage of participants |
| Part 1a: SAD Cohort 6 | Part 1: Percentage of Participants With Adverse Events | 50.0 Percentage of participants |
| Part 1c: Multiple Ascending Dose (MAD) Placebo | Part 1: Percentage of Participants With Adverse Events | 60.0 Percentage of participants |
| Part 1c: MAD Cohort 1 | Part 1: Percentage of Participants With Adverse Events | 83.3 Percentage of participants |
| Part 1c: MAD Cohort 2 | Part 1: Percentage of Participants With Adverse Events | 57.1 Percentage of participants |
| Part 1c: MAD Cohort 3 | Part 1: Percentage of Participants With Adverse Events | 28.6 Percentage of participants |
| Part 1c: MAD Cohort 4 | Part 1: Percentage of Participants With Adverse Events | 16.7 Percentage of participants |
| Part 1c: MAD Cohort 5 | Part 1: Percentage of Participants With Adverse Events | 16.7 Percentage of participants |
Primary
Part 2: Percentage of Participants With Adverse Events
Time frame: Up to Day 112
Population: The safety analysis population included all participants who received at least one dose of study drug, whether prematurely withdrawn from the study or not.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Percentage of Participants With Adverse Events | 50.0 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 2: Percentage of Participants With Adverse Events | 66.7 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Percentage of Participants With Adverse Events | 66.7 Percentage of participants |
| Part 1a: SAD Cohort 3 | Part 2: Percentage of Participants With Adverse Events | 83.3 Percentage of participants |
| Part 1a: SAD Cohort 4 | Part 2: Percentage of Participants With Adverse Events | 57.1 Percentage of participants |
| Part 1a: SAD Cohort 5 | Part 2: Percentage of Participants With Adverse Events | 33.3 Percentage of participants |
Primary
Part 2: Quantitative Plasma HBV DNA Level
Time frame: Baseline - Day 112
Population: The efficacy population included all participants who received at least one dose of RO7049389.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Quantitative Plasma HBV DNA Level | Day 84/Follow-up Day 56 | 5.15 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Quantitative Plasma HBV DNA Level | Day 112/Follow-up Day 84 | 5.09 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Quantitative Plasma HBV DNA Level | Baseline | 5.94 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Quantitative Plasma HBV DNA Level | Day 15 | 5.29 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Quantitative Plasma HBV DNA Level | Day 56/Follow-up Day 28 | 5.21 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Quantitative Plasma HBV DNA Level | Day 22 | 5.16 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Quantitative Plasma HBV DNA Level | Day 28 | 5.29 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Quantitative Plasma HBV DNA Level | Day 8 | 5.25 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Quantitative Plasma HBV DNA Level | Day 35/Follow-up Day 7 | 5.29 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 2: Quantitative Plasma HBV DNA Level | Day 15 | 2.00 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 2: Quantitative Plasma HBV DNA Level | Day 35/Follow-up Day 7 | 3.23 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 2: Quantitative Plasma HBV DNA Level | Day 112/Follow-up Day 84 | 5.89 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 2: Quantitative Plasma HBV DNA Level | Day 8 | 1.40 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 2: Quantitative Plasma HBV DNA Level | Baseline | 4.50 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 2: Quantitative Plasma HBV DNA Level | Day 84/Follow-up Day 56 | 5.76 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 2: Quantitative Plasma HBV DNA Level | Day 22 | 1.83 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 2: Quantitative Plasma HBV DNA Level | Day 56/Follow-up Day 28 | 4.07 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 2: Quantitative Plasma HBV DNA Level | Day 28 | 1.65 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Quantitative Plasma HBV DNA Level | Day 112/Follow-up Day 84 | 6.17 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Quantitative Plasma HBV DNA Level | Day 35/Follow-up Day 7 | 5.50 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Quantitative Plasma HBV DNA Level | Day 22 | 4.11 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Quantitative Plasma HBV DNA Level | Baseline | 7.80 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Quantitative Plasma HBV DNA Level | Day 84/Follow-up Day 56 | 5.68 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Quantitative Plasma HBV DNA Level | Day 15 | 4.58 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Quantitative Plasma HBV DNA Level | Day 56/Follow-up Day 28 | 6.53 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Quantitative Plasma HBV DNA Level | Day 28 | 3.64 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Quantitative Plasma HBV DNA Level | Day 8 | 5.27 Log10 IU/mL |
| Part 1a: SAD Cohort 3 | Part 2: Quantitative Plasma HBV DNA Level | Day 8 | 1.75 Log10 IU/mL |
| Part 1a: SAD Cohort 3 | Part 2: Quantitative Plasma HBV DNA Level | Baseline | 4.43 Log10 IU/mL |
| Part 1a: SAD Cohort 3 | Part 2: Quantitative Plasma HBV DNA Level | Day 15 | 1.46 Log10 IU/mL |
| Part 1a: SAD Cohort 3 | Part 2: Quantitative Plasma HBV DNA Level | Day 22 | 1.41 Log10 IU/mL |
| Part 1a: SAD Cohort 3 | Part 2: Quantitative Plasma HBV DNA Level | Day 28 | 1.30 Log10 IU/mL |
| Part 1a: SAD Cohort 3 | Part 2: Quantitative Plasma HBV DNA Level | Day 35/Follow-up Day 7 | 2.61 Log10 IU/mL |
| Part 1a: SAD Cohort 3 | Part 2: Quantitative Plasma HBV DNA Level | Day 56/Follow-up Day 28 | 3.43 Log10 IU/mL |
| Part 1a: SAD Cohort 3 | Part 2: Quantitative Plasma HBV DNA Level | Day 84/Follow-up Day 56 | 4.29 Log10 IU/mL |
| Part 1a: SAD Cohort 3 | Part 2: Quantitative Plasma HBV DNA Level | Day 112/Follow-up Day 84 | 4.45 Log10 IU/mL |
| Part 1a: SAD Cohort 4 | Part 2: Quantitative Plasma HBV DNA Level | Day 28 | 1.30 Log10 IU/mL |
| Part 1a: SAD Cohort 4 | Part 2: Quantitative Plasma HBV DNA Level | Day 22 | 1.41 Log10 IU/mL |
| Part 1a: SAD Cohort 4 | Part 2: Quantitative Plasma HBV DNA Level | Day 56/Follow-up Day 28 | 4.04 Log10 IU/mL |
| Part 1a: SAD Cohort 4 | Part 2: Quantitative Plasma HBV DNA Level | Day 15 | 1.30 Log10 IU/mL |
| Part 1a: SAD Cohort 4 | Part 2: Quantitative Plasma HBV DNA Level | Day 112/Follow-up Day 84 | 4.55 Log10 IU/mL |
| Part 1a: SAD Cohort 4 | Part 2: Quantitative Plasma HBV DNA Level | Day 84/Follow-up Day 56 | 4.73 Log10 IU/mL |
| Part 1a: SAD Cohort 4 | Part 2: Quantitative Plasma HBV DNA Level | Day 8 | 2.25 Log10 IU/mL |
| Part 1a: SAD Cohort 4 | Part 2: Quantitative Plasma HBV DNA Level | Baseline | 5.10 Log10 IU/mL |
| Part 1a: SAD Cohort 4 | Part 2: Quantitative Plasma HBV DNA Level | Day 35/Follow-up Day 7 | 2.98 Log10 IU/mL |
| Part 1a: SAD Cohort 5 | Part 2: Quantitative Plasma HBV DNA Level | Baseline | 7.14 Log10 IU/mL |
| Part 1a: SAD Cohort 5 | Part 2: Quantitative Plasma HBV DNA Level | Day 22 | 4.65 Log10 IU/mL |
| Part 1a: SAD Cohort 5 | Part 2: Quantitative Plasma HBV DNA Level | Day 28 | 4.43 Log10 IU/mL |
| Part 1a: SAD Cohort 5 | Part 2: Quantitative Plasma HBV DNA Level | Day 112/Follow-up Day 84 | 7.03 Log10 IU/mL |
| Part 1a: SAD Cohort 5 | Part 2: Quantitative Plasma HBV DNA Level | Day 84/Follow-up Day 56 | 6.83 Log10 IU/mL |
| Part 1a: SAD Cohort 5 | Part 2: Quantitative Plasma HBV DNA Level | Day 56/Follow-up Day 28 | 7.07 Log10 IU/mL |
| Part 1a: SAD Cohort 5 | Part 2: Quantitative Plasma HBV DNA Level | Day 15 | 4.90 Log10 IU/mL |
| Part 1a: SAD Cohort 5 | Part 2: Quantitative Plasma HBV DNA Level | Day 35/Follow-up Day 7 | 6.29 Log10 IU/mL |
| Part 1a: SAD Cohort 5 | Part 2: Quantitative Plasma HBV DNA Level | Day 8 | 5.21 Log10 IU/mL |
Primary
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
Population: The ITT population included all participants who were randomized and received at least one dose of study drug (RO7049389 or placebo). Participants were analyzed according to the treatment group to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 54 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 28 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 8 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 52 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 32 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 72 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 50 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 36 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 60 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 48 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 40 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 12 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 44 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 68 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 58 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 16 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 4 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Baseline | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 20 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 2 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 56 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 24 | 0 Percentage |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Proportion of Patients Achieving Functional Cure | Week 64 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 56 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Baseline | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 2 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 4 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 8 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 12 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 16 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 20 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 24 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 28 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 32 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 36 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 40 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 44 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 48 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 50 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 52 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 54 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 58 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 60 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 64 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 68 | 0 Percentage |
| Part 1a: SAD Cohort 1 | Part 3: Proportion of Patients Achieving Functional Cure | Week 72 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 64 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 52 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 24 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 2 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 54 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 20 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 16 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 56 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 12 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 72 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 58 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 8 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 68 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 40 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 60 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 44 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 36 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 4 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 48 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 32 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Baseline | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 50 | 0 Percentage |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Proportion of Patients Achieving Functional Cure | Week 28 | 0 Percentage |
Primary
Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389
Time frame: Up to Day 28
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389 | 171 L/hr | Geometric Coefficient of Variation 7.3 |
| Part 1a: SAD Cohort 1 | Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389 | 128 L/hr | Geometric Coefficient of Variation 67.8 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389 | 61.5 L/hr | Geometric Coefficient of Variation 72.1 |
| Part 1a: SAD Cohort 3 | Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389 | 64.9 L/hr | Geometric Coefficient of Variation 130.3 |
| Part 1a: SAD Cohort 4 | Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389 | 63.3 L/hr | Geometric Coefficient of Variation 69.7 |
| Part 1a: SAD Cohort 5 | Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389 | 64.9 L/hr | Geometric Coefficient of Variation 130.3 |
| Part 1a: SAD Cohort 6 | Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389 | 69.7 L/hr | Geometric Coefficient of Variation 122.3 |
Primary
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
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389 | 868 ng*hr/mL | Geometric Coefficient of Variation 6.6 |
| Part 1a: SAD Cohort 1 | Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389 | 4660 ng*hr/mL | Geometric Coefficient of Variation 53.8 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389 | 10900 ng*hr/mL | Geometric Coefficient of Variation 72 |
| Part 1a: SAD Cohort 3 | Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389 | 34300 ng*hr/mL | Geometric Coefficient of Variation 71.6 |
| Part 1a: SAD Cohort 4 | Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389 | 46200 ng*hr/mL | Geometric Coefficient of Variation 62.1 |
| Part 1a: SAD Cohort 5 | Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389 | 34300 ng*hr/mL | Geometric Coefficient of Variation 71.6 |
| Part 1a: SAD Cohort 6 | Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389 | 134000 ng*hr/mL | Geometric Coefficient of Variation 91.4 |
Primary
Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389
Time frame: Up to 28 days
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389 | 879 ng*hr/mL | Geometric Coefficient of Variation 7.5 |
| Part 1a: SAD Cohort 1 | Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389 | 4690 ng*hr/mL | Geometric Coefficient of Variation 53.2 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389 | 10900 ng*hr/mL | Geometric Coefficient of Variation 71.9 |
| Part 1a: SAD Cohort 3 | Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389 | 34400 ng*hr/mL | Geometric Coefficient of Variation 71.6 |
| Part 1a: SAD Cohort 4 | Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389 | 46300 ng*hr/mL | Geometric Coefficient of Variation 62 |
| Part 1a: SAD Cohort 5 | Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389 | 34400 ng*hr/mL | Geometric Coefficient of Variation 71.6 |
| Part 1a: SAD Cohort 6 | Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389 | 134000 ng*hr/mL | Geometric Coefficient of Variation 91.4 |
Primary
Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389
Time frame: Up to Day 28
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1a: SAD Cohort 1 | Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389 | 0.312 mg | Geometric Coefficient of Variation 69.6 |
| Part 1a: SAD Cohort 3 | Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389 | 1.88 mg | Geometric Coefficient of Variation 83.9 |
| Part 1a: SAD Cohort 4 | Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389 | 3.56 mg | Geometric Coefficient of Variation 92 |
| Part 1a: SAD Cohort 5 | Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389 | 1.88 mg | Geometric Coefficient of Variation 83.9 |
| Part 1a: SAD Cohort 6 | Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389 | 6.89 mg | Geometric Coefficient of Variation 101.8 |
Primary
Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389
Time frame: Up to Day 28
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389 | 3.34 Hours | Geometric Coefficient of Variation 35.3 |
| Part 1a: SAD Cohort 1 | Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389 | 8.80 Hours | Geometric Coefficient of Variation 81.1 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389 | 4.20 Hours | Geometric Coefficient of Variation 32 |
| Part 1a: SAD Cohort 3 | Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389 | 7.23 Hours | Geometric Coefficient of Variation 39.5 |
| Part 1a: SAD Cohort 4 | Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389 | 12.1 Hours | Geometric Coefficient of Variation 52.1 |
| Part 1a: SAD Cohort 5 | Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389 | 7.23 Hours | Geometric Coefficient of Variation 39.5 |
| Part 1a: SAD Cohort 6 | Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389 | 12.4 Hours | Geometric Coefficient of Variation 44.7 |
Primary
Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389
Time frame: Up to 28 days
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389 | 250 ng/mL | Geometric Coefficient of Variation 33.4 |
| Part 1a: SAD Cohort 1 | Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389 | 1900 ng/mL | Geometric Coefficient of Variation 79.7 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389 | 4610 ng/mL | Geometric Coefficient of Variation 75.6 |
| Part 1a: SAD Cohort 3 | Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389 | 8990 ng/mL | Geometric Coefficient of Variation 77.4 |
| Part 1a: SAD Cohort 4 | Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389 | 14700 ng/mL | Geometric Coefficient of Variation 67.6 |
| Part 1a: SAD Cohort 5 | Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389 | 8990 ng/mL | Geometric Coefficient of Variation 77.4 |
| Part 1a: SAD Cohort 6 | Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389 | 24800 ng/mL | Geometric Coefficient of Variation 63.9 |
Primary
Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389
Time frame: Up to Day 28
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part 1a: SAD Cohort 1 | Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389 | 1.60 mL/min | Geometric Coefficient of Variation 84.8 |
| Part 1a: SAD Cohort 3 | Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389 | 1.55 mL/min | Geometric Coefficient of Variation 42.9 |
| Part 1a: SAD Cohort 4 | Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389 | 1.41 mL/min | Geometric Coefficient of Variation 18.7 |
| Part 1a: SAD Cohort 5 | Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389 | 1.55 mL/min | Geometric Coefficient of Variation 42.9 |
| Part 1a: SAD Cohort 6 | Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389 | 0.82 mL/min | Geometric Coefficient of Variation 22.8 |
Primary
Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389
Time frame: Up to 28 days
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389 | 2.0 Hours |
| Part 1a: SAD Cohort 1 | Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389 | 1.25 Hours |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389 | 3.0 Hours |
| Part 1a: SAD Cohort 3 | Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389 | 1.5 Hours |
| Part 1a: SAD Cohort 4 | Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389 | 2.0 Hours |
| Part 1a: SAD Cohort 5 | Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389 | 1.5 Hours |
| Part 1a: SAD Cohort 6 | Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389 | 3.0 Hours |
Secondary
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
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1b: Food Effect on AUCinf of RO7049389 | 2.17 geometric mean ratio |
Secondary
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
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1b: Food Effect on Cmax of RO7049389 | 2.42 geometric mean ratio |
Secondary
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
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis. Cohort 4 was terminated after 3 days of administration and could not be included in analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: Accumulation Ratio of RO7049389 | 1.45 Geometric mean ratio | Geometric Coefficient of Variation 24.3 |
| Part 1a: SAD Cohort 1 | Part 1c: Accumulation Ratio of RO7049389 | 1.05 Geometric mean ratio | Geometric Coefficient of Variation 31.1 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: Accumulation Ratio of RO7049389 | 0.880 Geometric mean ratio | Geometric Coefficient of Variation 35.6 |
| Part 1a: SAD Cohort 3 | Part 1c: Accumulation Ratio of RO7049389 | 1.09 Geometric mean ratio | Geometric Coefficient of Variation 37.4 |
Secondary
Part 1c: Ae of RO7049389
Time frame: Up to Day 14
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: Ae of RO7049389 | Day 1 | 0.0926 mg | Geometric Coefficient of Variation 90.7 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: Ae of RO7049389 | Day 14 | 0.243 mg | Geometric Coefficient of Variation 89.5 |
| Part 1a: SAD Cohort 1 | Part 1c: Ae of RO7049389 | Day 14 | 0.189 mg | Geometric Coefficient of Variation 60.7 |
| Part 1a: SAD Cohort 1 | Part 1c: Ae of RO7049389 | Day 1 | 0.0900 mg | Geometric Coefficient of Variation 56 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: Ae of RO7049389 | Day 1 | 0.859 mg | Geometric Coefficient of Variation 60.9 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: Ae of RO7049389 | Day 14 | 1.26 mg | Geometric Coefficient of Variation 53.8 |
| Part 1a: SAD Cohort 3 | Part 1c: Ae of RO7049389 | Day 1 | 3.58 mg | Geometric Coefficient of Variation 63.4 |
| Part 1a: SAD Cohort 4 | Part 1c: Ae of RO7049389 | Day 14 | 3.68 mg | Geometric Coefficient of Variation 26.3 |
| Part 1a: SAD Cohort 4 | Part 1c: Ae of RO7049389 | Day 1 | 1.77 mg | Geometric Coefficient of Variation 35.9 |
Secondary
Part 1c: AUC0-12hr of RO7049389
Time frame: Up to Day 14
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: AUC0-12hr of RO7049389 | Day 1 | 1304.09 ng*hr/mL | Geometric Coefficient of Variation 31.9 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: AUC0-12hr of RO7049389 | Day 14 | 1806.59 ng*hr/mL | Geometric Coefficient of Variation 25.6 |
| Part 1a: SAD Cohort 1 | Part 1c: AUC0-12hr of RO7049389 | Day 14 | 1573.32 ng*hr/mL | Geometric Coefficient of Variation 27.5 |
| Part 1a: SAD Cohort 1 | Part 1c: AUC0-12hr of RO7049389 | Day 1 | 1819.92 ng*hr/mL | Geometric Coefficient of Variation 46.1 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: AUC0-12hr of RO7049389 | Day 1 | 9760.31 ng*hr/mL | Geometric Coefficient of Variation 55.7 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: AUC0-12hr of RO7049389 | Day 14 | 6511.21 ng*hr/mL | Geometric Coefficient of Variation 29 |
| Part 1a: SAD Cohort 3 | Part 1c: AUC0-12hr of RO7049389 | Day 1 | 32459.87 ng*hr/mL | Geometric Coefficient of Variation 42.6 |
| Part 1a: SAD Cohort 4 | Part 1c: AUC0-12hr of RO7049389 | Day 14 | 28051.71 ng*hr/mL | Geometric Coefficient of Variation 32.5 |
| Part 1a: SAD Cohort 4 | Part 1c: AUC0-12hr of RO7049389 | Day 1 | 27041.94 ng*hr/mL | Geometric Coefficient of Variation 33.6 |
Secondary
Part 1c: AUCinf of Midazolam
This endpoint presents the geometric mean ratio (after RO7049389/before RO7049389).
Time frame: Up to Day 14
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis. Cohort 4 was terminated after 3 days of administration and could not be included in analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: AUCinf of Midazolam | 1.10 Ratio |
| Part 1a: SAD Cohort 1 | Part 1c: AUCinf of Midazolam | 1.18 Ratio |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: AUCinf of Midazolam | 1.25 Ratio |
| Part 1a: SAD Cohort 3 | Part 1c: AUCinf of Midazolam | 1.16 Ratio |
Secondary
Part 1c: CLr of RO7049389
Time frame: Up to Day 14
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: CLr of RO7049389 | Day 1 | 1.06 mL/min | Geometric Coefficient of Variation 74.2 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: CLr of RO7049389 | Day 14 | 1.96 mL/min | Geometric Coefficient of Variation 75.2 |
| Part 1a: SAD Cohort 1 | Part 1c: CLr of RO7049389 | Day 14 | 1.87 mL/min | Geometric Coefficient of Variation 51.7 |
| Part 1a: SAD Cohort 1 | Part 1c: CLr of RO7049389 | Day 1 | 1.08 mL/min | Geometric Coefficient of Variation 82.6 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: CLr of RO7049389 | Day 1 | 1.43 mL/min | Geometric Coefficient of Variation 27 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: CLr of RO7049389 | Day 14 | 3.01 mL/min | Geometric Coefficient of Variation 46.9 |
| Part 1a: SAD Cohort 3 | Part 1c: CLr of RO7049389 | Day 1 | 2.04 mL/min | Geometric Coefficient of Variation 54.7 |
| Part 1a: SAD Cohort 4 | Part 1c: CLr of RO7049389 | Day 14 | 2.32 mL/min | Geometric Coefficient of Variation 35 |
| Part 1a: SAD Cohort 4 | Part 1c: CLr of RO7049389 | Day 1 | 1.19 mL/min | Geometric Coefficient of Variation 48.6 |
Secondary
Part 1c: Cmax of Midazolam
This endpoint presents the geometric mean ratio (after RO7049389/before RO7049389).
Time frame: Up to Day 14
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis. Cohort 4 was terminated after 3 days of administration and could not be included in analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: Cmax of Midazolam | 0.892 Ratio |
| Part 1a: SAD Cohort 1 | Part 1c: Cmax of Midazolam | 1.01 Ratio |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: Cmax of Midazolam | 1.12 Ratio |
| Part 1a: SAD Cohort 3 | Part 1c: Cmax of Midazolam | 0.940 Ratio |
Secondary
Part 1c: Cmax of RO7049389
Time frame: Up to Day 14
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: Cmax of RO7049389 | Day 1 | 483 ng/mL | Geometric Coefficient of Variation 42.5 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: Cmax of RO7049389 | Day 14 | 735 ng/mL | Geometric Coefficient of Variation 19.9 |
| Part 1a: SAD Cohort 1 | Part 1c: Cmax of RO7049389 | Day 14 | 583 ng/mL | Geometric Coefficient of Variation 41.3 |
| Part 1a: SAD Cohort 1 | Part 1c: Cmax of RO7049389 | Day 1 | 840 ng/mL | Geometric Coefficient of Variation 41.7 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: Cmax of RO7049389 | Day 1 | 4840 ng/mL | Geometric Coefficient of Variation 53.7 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: Cmax of RO7049389 | Day 14 | 2720 ng/mL | Geometric Coefficient of Variation 49 |
| Part 1a: SAD Cohort 3 | Part 1c: Cmax of RO7049389 | Day 1 | 14500 ng/mL | Geometric Coefficient of Variation 39.5 |
| Part 1a: SAD Cohort 4 | Part 1c: Cmax of RO7049389 | Day 14 | 9960 ng/mL | Geometric Coefficient of Variation 32.7 |
| Part 1a: SAD Cohort 4 | Part 1c: Cmax of RO7049389 | Day 1 | 10600 ng/mL | Geometric Coefficient of Variation 42.2 |
Secondary
Part 1c: Ctrough of RO7049389
Time frame: Up to Day 14
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis. Cohort 4 was terminated after 3 days of administration and could not be included in analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: Ctrough of RO7049389 | 12.1 ng/mL | Geometric Coefficient of Variation 45.1 |
| Part 1a: SAD Cohort 1 | Part 1c: Ctrough of RO7049389 | 15.2 ng/mL | Geometric Coefficient of Variation 27.8 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: Ctrough of RO7049389 | 42.1 ng/mL | Geometric Coefficient of Variation 12.8 |
| Part 1a: SAD Cohort 3 | Part 1c: Ctrough of RO7049389 | 88.9 ng/mL | Geometric Coefficient of Variation 27.6 |
Secondary
Part 1c: T1/2 of RO7049389
Time frame: Up to Day 14
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: T1/2 of RO7049389 | Day 1 | 2.27 Hours | Geometric Coefficient of Variation 24.1 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: T1/2 of RO7049389 | Day 14 | 5.79 Hours | Geometric Coefficient of Variation 40.7 |
| Part 1a: SAD Cohort 1 | Part 1c: T1/2 of RO7049389 | Day 14 | 5.17 Hours | Geometric Coefficient of Variation 26.8 |
| Part 1a: SAD Cohort 1 | Part 1c: T1/2 of RO7049389 | Day 1 | 2.44 Hours | Geometric Coefficient of Variation 12.6 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: T1/2 of RO7049389 | Day 1 | 2.09 Hours | Geometric Coefficient of Variation 18.5 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: T1/2 of RO7049389 | Day 14 | 5.08 Hours | Geometric Coefficient of Variation 10.5 |
| Part 1a: SAD Cohort 3 | Part 1c: T1/2 of RO7049389 | Day 1 | 1.70 Hours | Geometric Coefficient of Variation 30.4 |
| Part 1a: SAD Cohort 4 | Part 1c: T1/2 of RO7049389 | Day 14 | 5.73 Hours | Geometric Coefficient of Variation 28.9 |
| Part 1a: SAD Cohort 4 | Part 1c: T1/2 of RO7049389 | Day 1 | 1.53 Hours | Geometric Coefficient of Variation 22.5 |
Secondary
Part 1c: Tmax of RO7049389
Time frame: Up to Day 14
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: Tmax of RO7049389 | Day 1 | 2.0 hours |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 1c: Tmax of RO7049389 | Day 14 | 1.5 hours |
| Part 1a: SAD Cohort 1 | Part 1c: Tmax of RO7049389 | Day 14 | 2.0 hours |
| Part 1a: SAD Cohort 1 | Part 1c: Tmax of RO7049389 | Day 1 | 2.0 hours |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: Tmax of RO7049389 | Day 1 | 3.0 hours |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 1c: Tmax of RO7049389 | Day 14 | 3.0 hours |
| Part 1a: SAD Cohort 3 | Part 1c: Tmax of RO7049389 | Day 1 | 3.0 hours |
| Part 1a: SAD Cohort 4 | Part 1c: Tmax of RO7049389 | Day 14 | 3.0 hours |
| Part 1a: SAD Cohort 4 | Part 1c: Tmax of RO7049389 | Day 1 | 3.0 hours |
Secondary
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
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Accumulation Ratio of RO7049389 | 1.01 Geometric mean ratio | Geometric Coefficient of Variation 81.3 |
| Part 1a: SAD Cohort 1 | Part 2: Accumulation Ratio of RO7049389 | 0.971 Geometric mean ratio | Geometric Coefficient of Variation 58.2 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Accumulation Ratio of RO7049389 | 1.65 Geometric mean ratio | Geometric Coefficient of Variation 109.8 |
| Part 1a: SAD Cohort 3 | Part 2: Accumulation Ratio of RO7049389 | 0.823 Geometric mean ratio | Geometric Coefficient of Variation 77 |
| Part 1a: SAD Cohort 4 | Part 2: Accumulation Ratio of RO7049389 | 0.917 Geometric mean ratio | Geometric Coefficient of Variation 40.9 |
Secondary
Part 2: AUCtau of RO7049389
Time frame: Up to Day 28
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: AUCtau of RO7049389 | Day 1 | 2870 ng*hr/mL | Geometric Coefficient of Variation 50.2 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: AUCtau of RO7049389 | Day 28 | 3350 ng*hr/mL | Geometric Coefficient of Variation 47.7 |
| Part 1a: SAD Cohort 1 | Part 2: AUCtau of RO7049389 | Day 1 | 19900 ng*hr/mL | Geometric Coefficient of Variation 78.6 |
| Part 1a: SAD Cohort 1 | Part 2: AUCtau of RO7049389 | Day 28 | 22400 ng*hr/mL | Geometric Coefficient of Variation 70.5 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: AUCtau of RO7049389 | Day 1 | 11500 ng*hr/mL | Geometric Coefficient of Variation 65.5 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: AUCtau of RO7049389 | Day 28 | 14600 ng*hr/mL | Geometric Coefficient of Variation 78 |
| Part 1a: SAD Cohort 3 | Part 2: AUCtau of RO7049389 | Day 28 | 133000 ng*hr/mL | Geometric Coefficient of Variation 50 |
| Part 1a: SAD Cohort 3 | Part 2: AUCtau of RO7049389 | Day 1 | 80000 ng*hr/mL | Geometric Coefficient of Variation 71.2 |
| Part 1a: SAD Cohort 4 | Part 2: AUCtau of RO7049389 | Day 1 | 3500 ng*hr/mL | Geometric Coefficient of Variation 76.7 |
| Part 1a: SAD Cohort 4 | Part 2: AUCtau of RO7049389 | Day 28 | 3480 ng*hr/mL | Geometric Coefficient of Variation 56.9 |
Secondary
Part 2: Cmax of RO7049389
Time frame: Up to Day 28
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Cmax of RO7049389 | Day 1 | 1450 ng/mL | Geometric Coefficient of Variation 69.1 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Cmax of RO7049389 | Day 28 | 1500 ng/mL | Geometric Coefficient of Variation 60.3 |
| Part 1a: SAD Cohort 1 | Part 2: Cmax of RO7049389 | Day 1 | 8110 ng/mL | Geometric Coefficient of Variation 59.7 |
| Part 1a: SAD Cohort 1 | Part 2: Cmax of RO7049389 | Day 28 | 8580 ng/mL | Geometric Coefficient of Variation 63.7 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Cmax of RO7049389 | Day 1 | 5030 ng/mL | Geometric Coefficient of Variation 42.7 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Cmax of RO7049389 | Day 28 | 4890 ng/mL | Geometric Coefficient of Variation 76.9 |
| Part 1a: SAD Cohort 3 | Part 2: Cmax of RO7049389 | Day 28 | 29800 ng/mL | Geometric Coefficient of Variation 15.2 |
| Part 1a: SAD Cohort 3 | Part 2: Cmax of RO7049389 | Day 1 | 23900 ng/mL | Geometric Coefficient of Variation 41.8 |
| Part 1a: SAD Cohort 4 | Part 2: Cmax of RO7049389 | Day 1 | 910 ng/mL | Geometric Coefficient of Variation 89.1 |
| Part 1a: SAD Cohort 4 | Part 2: Cmax of RO7049389 | Day 28 | 998 ng/mL | Geometric Coefficient of Variation 52.8 |
Secondary
Part 2: Ctrough of RO7049389
Time frame: Up to Day 28
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Ctrough of RO7049389 | 26.7 ng/mL | Geometric Coefficient of Variation 72.7 |
| Part 1a: SAD Cohort 1 | Part 2: Ctrough of RO7049389 | 68.2 ng/mL | Geometric Coefficient of Variation 89.2 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Ctrough of RO7049389 | 7.94 ng/mL | Geometric Coefficient of Variation 60.6 |
| Part 1a: SAD Cohort 3 | Part 2: Ctrough of RO7049389 | 27.0 ng/mL | Geometric Coefficient of Variation 42.3 |
| Part 1a: SAD Cohort 4 | Part 2: Ctrough of RO7049389 | 3.37 ng/mL | Geometric Coefficient of Variation 88.1 |
Secondary
Part 2: HBV DNA < Lower Limit of Quantification (LLOQ)
Time frame: Baseline - Day 112/Follow-up Day 84
Population: The efficacy population included all participants who received at least one dose of RO7049389.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 84/Follow-up Day 56 | 0 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 112/Follow-up Day 84 | 0 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 15 | 0 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 35/Follow-up Day 7 | 0 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 56/Follow-up Day 28 | 0 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 28 | 0 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 8 | 0 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Baseline | 0 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 22 | 0 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 112/Follow-up Day 84 | 0 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 35/Follow-up Day 7 | 16.7 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 8 | 33.3 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 15 | 50.0 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Baseline | 0 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 84/Follow-up Day 56 | 0 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 22 | 50.0 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 56/Follow-up Day 28 | 0 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 28 | 50.0 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 8 | 0 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 35/Follow-up Day 7 | 0 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 22 | 0 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 84/Follow-up Day 56 | 0 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 112/Follow-up Day 84 | 0 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 15 | 0 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 56/Follow-up Day 28 | 0 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 28 | 16.7 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Baseline | 0 Percentage of participants |
| Part 1a: SAD Cohort 3 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 35/Follow-up Day 7 | 0 Percentage of participants |
| Part 1a: SAD Cohort 3 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Baseline | 0 Percentage of participants |
| Part 1a: SAD Cohort 3 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 8 | 50.0 Percentage of participants |
| Part 1a: SAD Cohort 3 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 15 | 50.0 Percentage of participants |
| Part 1a: SAD Cohort 3 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 22 | 50.0 Percentage of participants |
| Part 1a: SAD Cohort 3 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 28 | 66.7 Percentage of participants |
| Part 1a: SAD Cohort 3 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 56/Follow-up Day 28 | 0 Percentage of participants |
| Part 1a: SAD Cohort 3 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 84/Follow-up Day 56 | 0 Percentage of participants |
| Part 1a: SAD Cohort 3 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 112/Follow-up Day 84 | 0 Percentage of participants |
| Part 1a: SAD Cohort 4 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 28 | 57.1 Percentage of participants |
| Part 1a: SAD Cohort 4 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 22 | 42.9 Percentage of participants |
| Part 1a: SAD Cohort 4 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 56/Follow-up Day 28 | 0 Percentage of participants |
| Part 1a: SAD Cohort 4 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 15 | 57.1 Percentage of participants |
| Part 1a: SAD Cohort 4 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 112/Follow-up Day 84 | 0 Percentage of participants |
| Part 1a: SAD Cohort 4 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 84/Follow-up Day 56 | 0 Percentage of participants |
| Part 1a: SAD Cohort 4 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 8 | 28.6 Percentage of participants |
| Part 1a: SAD Cohort 4 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Baseline | 0 Percentage of participants |
| Part 1a: SAD Cohort 4 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 35/Follow-up Day 7 | 0 Percentage of participants |
| Part 1a: SAD Cohort 5 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Baseline | 0 Percentage of participants |
| Part 1a: SAD Cohort 5 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 22 | 16.7 Percentage of participants |
| Part 1a: SAD Cohort 5 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 35/Follow-up Day 7 | 0 Percentage of participants |
| Part 1a: SAD Cohort 5 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 112/Follow-up Day 84 | 0 Percentage of participants |
| Part 1a: SAD Cohort 5 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 84/Follow-up Day 56 | 0 Percentage of participants |
| Part 1a: SAD Cohort 5 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 56/Follow-up Day 28 | 0 Percentage of participants |
| Part 1a: SAD Cohort 5 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 15 | 16.7 Percentage of participants |
| Part 1a: SAD Cohort 5 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 28 | 16.7 Percentage of participants |
| Part 1a: SAD Cohort 5 | Part 2: HBV DNA < Lower Limit of Quantification (LLOQ) | Day 8 | 0 Percentage of participants |
Secondary
Part 2: T1/2 of RO7049389
Time frame: Up to Day 28
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: T1/2 of RO7049389 | Day 1 | 1.68 Hours | Geometric Coefficient of Variation 18 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: T1/2 of RO7049389 | Day 28 | 3.38 Hours | Geometric Coefficient of Variation 24.1 |
| Part 1a: SAD Cohort 1 | Part 2: T1/2 of RO7049389 | Day 1 | 1.15 Hours | Geometric Coefficient of Variation 27.6 |
| Part 1a: SAD Cohort 1 | Part 2: T1/2 of RO7049389 | Day 28 | 3.26 Hours | Geometric Coefficient of Variation 28.8 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: T1/2 of RO7049389 | Day 1 | 1.09 Hours | Geometric Coefficient of Variation 22.4 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: T1/2 of RO7049389 | Day 28 | 3.70 Hours | Geometric Coefficient of Variation 26.1 |
| Part 1a: SAD Cohort 3 | Part 2: T1/2 of RO7049389 | Day 28 | 2.33 Hours | Geometric Coefficient of Variation 20.1 |
| Part 1a: SAD Cohort 3 | Part 2: T1/2 of RO7049389 | Day 1 | 1.40 Hours | Geometric Coefficient of Variation 34.5 |
| Part 1a: SAD Cohort 4 | Part 2: T1/2 of RO7049389 | Day 1 | 2.33 Hours | Geometric Coefficient of Variation 55.2 |
| Part 1a: SAD Cohort 4 | Part 2: T1/2 of RO7049389 | Day 28 | 3.81 Hours | Geometric Coefficient of Variation 24.6 |
Secondary
Part 2: Tmax of RO7049389
Time frame: Up to Day 28
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Tmax of RO7049389 | Day 1 | 2.0 Hours |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 2: Tmax of RO7049389 | Day 28 | 2.5 Hours |
| Part 1a: SAD Cohort 1 | Part 2: Tmax of RO7049389 | Day 1 | 3.0 Hours |
| Part 1a: SAD Cohort 1 | Part 2: Tmax of RO7049389 | Day 28 | 2.5 Hours |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Tmax of RO7049389 | Day 1 | 1.97 Hours |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 2: Tmax of RO7049389 | Day 28 | 2.0 Hours |
| Part 1a: SAD Cohort 3 | Part 2: Tmax of RO7049389 | Day 28 | 2.03 Hours |
| Part 1a: SAD Cohort 3 | Part 2: Tmax of RO7049389 | Day 1 | 1.98 Hours |
| Part 1a: SAD Cohort 4 | Part 2: Tmax of RO7049389 | Day 1 | 1.5 Hours |
| Part 1a: SAD Cohort 4 | Part 2: Tmax of RO7049389 | Day 28 | 1.5 Hours |
Secondary
Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation
Time frame: Week 12 - Week 72
Population: This endpoint includes participants from Part 3 with elevated ALT at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1a: SAD Cohort 1 | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 36 | 88.89 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 56 | 77.78 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 24 | 88.89 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 64 | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 48 | 88.89 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 72 | 87.5 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 12 | 66.67 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 72 | 92.59 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 12 | 35.71 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 24 | 62.96 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 36 | 77.78 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 48 | 85.19 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 56 | 81.48 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation | Week 64 | 92.59 Percentage of participants |
Secondary
Part 3: AUCtau of RO7049389
Time frame: Day 1 - Week 48
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: AUCtau of RO7049389 | Week 48 | 14100 h*ng/mL | Geometric Coefficient of Variation 84.8 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: AUCtau of RO7049389 | Week 24 | 15400 h*ng/mL | Geometric Coefficient of Variation 121.3 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: AUCtau of RO7049389 | Day 1 | 18700 h*ng/mL | Geometric Coefficient of Variation 105.1 |
| Part 1a: SAD Cohort 1 | Part 3: AUCtau of RO7049389 | Week 24 | 10500 h*ng/mL | Geometric Coefficient of Variation 241.8 |
| Part 1a: SAD Cohort 1 | Part 3: AUCtau of RO7049389 | Day 1 | 16700 h*ng/mL | Geometric Coefficient of Variation 79.3 |
| Part 1a: SAD Cohort 1 | Part 3: AUCtau of RO7049389 | Week 4 | 13600 h*ng/mL | Geometric Coefficient of Variation 117.2 |
| Part 1a: SAD Cohort 1 | Part 3: AUCtau of RO7049389 | Week 48 | 16000 h*ng/mL | Geometric Coefficient of Variation 121.3 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: AUCtau of RO7049389 | Day 1 | 20900 h*ng/mL | Geometric Coefficient of Variation 107.4 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: AUCtau of RO7049389 | Week 48 | 11700 h*ng/mL | Geometric Coefficient of Variation 107.6 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: AUCtau of RO7049389 | Week 24 | 13200 h*ng/mL | Geometric Coefficient of Variation 88.2 |
Secondary
Part 3: Cmax of RO7049389
Time frame: Day 1 - Week 48
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Cmax of RO7049389 | Week 48 | 5410 ng/mL | Geometric Coefficient of Variation 88.4 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Cmax of RO7049389 | Week 24 | 2500 ng/mL | Geometric Coefficient of Variation 2040.7 |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Cmax of RO7049389 | Day 1 | 7140 ng/mL | Geometric Coefficient of Variation 107.6 |
| Part 1a: SAD Cohort 1 | Part 3: Cmax of RO7049389 | Week 24 | 3900 ng/mL | Geometric Coefficient of Variation 126.9 |
| Part 1a: SAD Cohort 1 | Part 3: Cmax of RO7049389 | Day 1 | 5390 ng/mL | Geometric Coefficient of Variation 94.3 |
| Part 1a: SAD Cohort 1 | Part 3: Cmax of RO7049389 | Week 4 | 4630 ng/mL | Geometric Coefficient of Variation 92.8 |
| Part 1a: SAD Cohort 1 | Part 3: Cmax of RO7049389 | Week 48 | 3510 ng/mL | Geometric Coefficient of Variation 246.1 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Cmax of RO7049389 | Day 1 | 5910 ng/mL | Geometric Coefficient of Variation 116.8 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Cmax of RO7049389 | Week 48 | 3570 ng/mL | Geometric Coefficient of Variation 133.6 |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Cmax of RO7049389 | Week 24 | 4260 ng/mL | Geometric Coefficient of Variation 89.4 |
Secondary
Part 3: HBV Core-Related Antigen (HBcrAg) Levels
Time frame: Baseline - Week 72
Population: The ITT population included all participants who were randomized and received at least one dose of study drug (RO7049389 or placebo). Participants were analyzed according to the treatment group to which they were randomized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 54 | 3.30 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 28 | 4.05 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 8 | 4.30 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 52 | 3.60 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 32 | 4.20 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 72 | 4.20 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 50 | 4.00 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 36 | 4.05 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 60 | 4.15 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 48 | 4.10 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 40 | 4.10 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 12 | 4.30 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 44 | 4.35 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 68 | 3.80 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 58 | 2.50 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 16 | 4.05 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 4 | 4.20 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Baseline | 4.10 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 20 | 4.10 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 2 | 4.10 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 56 | 4.15 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 24 | 4.20 Log10 U/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 64 | 4.20 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 56 | 5.00 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Baseline | 6.15 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 2 | 5.95 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 4 | 5.55 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 8 | 5.25 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 12 | 5.15 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 16 | 5.50 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 20 | 5.00 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 24 | 5.10 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 28 | 5.00 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 32 | 4.85 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 36 | 5.10 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 40 | 4.90 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 44 | 4.80 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 48 | 5.10 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 50 | 5.05 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 52 | 5.05 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 54 | 3.90 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 58 | 5.30 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 60 | 3.60 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 64 | 4.40 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 68 | 5.30 Log10 U/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 72 | 4.80 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 64 | 5.15 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 52 | 3.10 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 24 | 5.70 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 2 | 7.80 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 54 | 3.10 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 20 | 5.90 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 16 | 6.20 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 56 | 5.50 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 12 | 6.30 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 72 | 4.70 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 58 | 3.20 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 8 | 6.70 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 68 | 3.20 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 40 | 5.45 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 60 | 2.90 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 44 | 5.35 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 36 | 5.45 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 4 | 7.00 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 48 | 5.45 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 32 | 5.40 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Baseline | 7.95 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 50 | 3.10 Log10 U/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV Core-Related Antigen (HBcrAg) Levels | Week 28 | 5.60 Log10 U/mL |
Secondary
Part 3: HBV DNA Level
Time frame: Baseline - Week 72
Population: The ITT population included all participants who were randomized and received at least one dose of study drug (RO7049389 or placebo). Participants were analyzed according to the treatment group to which they were randomized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 52 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 28 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 64 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 50 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 32 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 8 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 48 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 36 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 72 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 44 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 40 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 60 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 12 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 68 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 58 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 16 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Baseline | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 56 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 20 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 4 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 54 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 24 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA Level | Week 2 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 16 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Baseline | 6.06 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 2 | 3.14 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 4 | 1.99 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 8 | 1.41 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 12 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 20 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 24 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 28 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 32 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 36 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 40 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 52 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 44 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 48 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 50 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 54 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 56 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 58 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 60 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 64 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 68 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA Level | Week 72 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 24 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 52 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 20 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 64 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 54 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 16 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 2 | 3.89 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 56 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 12 | 1.44 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 72 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 58 | 2.09 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 8 | 1.54 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 40 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 68 | 2.67 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 36 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 60 | 2.52 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 44 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 32 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 4 | 2.76 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 48 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 28 | 1.28 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Baseline | 7.37 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA Level | Week 50 | 0.95 Log10 copies/mL |
Secondary
Part 3: HBV DNA < Lower Limit of Quantification (LLOQ)
Time frame: Baseline - Week 72
Population: The ITT population included all participants who were randomized and received at least one dose of study drug (RO7049389 or placebo). Participants were analyzed according to the treatment group to which they were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 54 | 88.9 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 28 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 8 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 52 | 90 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 32 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 72 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 50 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 36 | 96.7 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 60 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 48 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 40 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 12 | 96.4 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 44 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 68 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 58 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 16 | 96.7 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 4 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Baseline | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 20 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 2 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 56 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 24 | 100 Percentage of participants |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 64 | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 56 | 88.9 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Baseline | 0 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 2 | 10 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 4 | 30 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 8 | 40 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 12 | 70 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 16 | 77.8 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 20 | 90 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 24 | 88.9 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 28 | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 32 | 87.5 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 36 | 90 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 40 | 77.8 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 44 | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 48 | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 50 | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 52 | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 54 | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 58 | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 60 | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 64 | 83.3 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 68 | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 72 | 77.8 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 64 | 67.9 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 52 | 80 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 24 | 51.7 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 2 | 10.3 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 54 | 80 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 20 | 55.2 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 16 | 51.7 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 56 | 64.3 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 12 | 43.3 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 72 | 78.6 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 58 | 40 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 8 | 41.4 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 68 | 40 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 40 | 71.4 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 60 | 20 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 44 | 71.4 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 36 | 67.9 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 4 | 16.7 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 48 | 81.5 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 32 | 64.3 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Baseline | 0 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 50 | 100 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV DNA < Lower Limit of Quantification (LLOQ) | Week 28 | 55.2 Percentage of participants |
Secondary
Part 3: HBV RNA Level
Time frame: Baseline - Week 72
Population: The ITT population included all participants who were randomized and received at least one dose of study drug (RO7049389 or placebo). Participants were analyzed according to the treatment group to which they were randomized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 52 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 28 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 64 | 0.99 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 50 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 32 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 4 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 48 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 36 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Baseline | 0.99 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 44 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 40 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 60 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 8 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 72 | 0.99 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 58 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 12 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 68 | 1.28 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 56 | 0.99 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 16 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 2 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 54 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 20 | 0.69 Log10 copies/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: HBV RNA Level | Week 24 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 56 | 1.94 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Baseline | 4.02 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 2 | 1.04 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 4 | 0.84 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 8 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 12 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 16 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 24 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 28 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 32 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 36 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 40 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 44 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 48 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 50 | 1.02 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 52 | 1.46 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 54 | 2.08 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 20 | 0.69 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 58 | 1.75 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 60 | 1.25 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 64 | 1.28 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 68 | 1.99 Log10 copies/mL |
| Part 1a: SAD Cohort 1 | Part 3: HBV RNA Level | Week 72 | 1.77 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 20 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 52 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 16 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 64 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 54 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 12 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Baseline | 5.30 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 56 | 1.54 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 8 | 1.54 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 72 | 1.08 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 58 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 4 | 1.93 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 40 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 36 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 68 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 44 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 32 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 60 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 48 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 28 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 2 | 2.37 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 50 | 0.99 Log10 copies/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: HBV RNA Level | Week 24 | 0.99 Log10 copies/mL |
Secondary
Part 3: Hepatitis B e-Antigen (HBeAg) Levels
Time frame: Baseline - Week 72
Population: The population for this endpoint included participants in Part 3 that were HBeAg+ at baseline.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 48 | 0.15 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 24 | 0.10 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 2 | 0.16 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 44 | 0.16 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 28 | 0.12 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 56 | 0.09 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 40 | 0.13 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 32 | 0.14 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 8 | 0.15 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 36 | 0.15 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 72 | 0.08 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 54 | -0.54 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 12 | 0.12 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 64 | 0.14 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 52 | -0.54 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 16 | 0.12 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Baseline | 0.17 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 50 | -0.53 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 20 | 0.06 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 4 | 0.17 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 16 | -0.04 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Baseline | 1.07 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 2 | 1.01 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 4 | 0.60 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 8 | 0.33 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 12 | 0.17 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 20 | -0.12 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 24 | -0.24 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 28 | -0.32 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 32 | -0.40 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 36 | -0.43 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 40 | -0.49 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 44 | -0.50 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 48 | -0.52 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 50 | -0.71 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 52 | -0.71 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 54 | -0.54 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 56 | -0.54 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 58 | -0.54 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 60 | -0.54 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 64 | -0.54 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 68 | -0.54 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 72 | -0.35 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 60 | 1.70 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 50 | -0.47 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 12 | 2.02 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 2 | 2.79 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 52 | -0.54 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 8 | 2.24 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Baseline | 2.84 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 54 | -0.49 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 4 | 2.57 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 64 | 0.36 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 32 | 1.12 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 56 | 0.74 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 36 | 0.96 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 28 | 1.32 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 72 | -0.23 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 40 | 0.83 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 24 | 1.31 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 58 | 1.23 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 44 | 0.82 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 20 | 1.40 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 68 | -0.54 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 48 | 0.69 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B e-Antigen (HBeAg) Levels | Week 16 | 1.81 Log10 IU/mL |
Secondary
Part 3: Hepatitis B Surface Antigen (HBsAg) Level
Time frame: Baseline - Week 72
Population: The ITT population included all participants who were randomized and received at least one dose of study drug (RO7049389 or placebo). Participants were analyzed according to the treatment group to which they were randomized.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 54 | 2.98 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 28 | 3.04 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 8 | 3.00 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 52 | 2.89 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 32 | 2.99 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 72 | 2.95 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 50 | 2.96 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 36 | 2.98 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 60 | 3.84 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 48 | 2.99 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 40 | 3.03 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 12 | 3.02 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 44 | 3.00 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 68 | 2.65 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 58 | 2.67 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 16 | 3.03 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 4 | 3.08 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Baseline | 3.04 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 20 | 3.05 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 2 | 3.08 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 56 | 2.97 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 24 | 2.99 Log10 IU/mL |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 64 | 2.98 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 56 | 3.75 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Baseline | 3.51 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 2 | 3.51 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 4 | 3.47 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 8 | 3.49 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 12 | 3.52 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 16 | 3.22 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 20 | 3.48 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 24 | 3.84 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 28 | 3.39 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 32 | 3.52 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 36 | 3.50 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 40 | 3.81 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 44 | 3.81 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 48 | 3.53 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 50 | 3.21 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 52 | 3.21 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 54 | 3.51 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 58 | 3.15 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 60 | 3.20 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 64 | 3.53 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 68 | 3.12 Log10 IU/mL |
| Part 1a: SAD Cohort 1 | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 72 | 3.71 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 64 | 2.83 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 52 | 1.32 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 24 | 3.15 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 2 | 4.14 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 54 | 1.41 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 20 | 3.26 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 16 | 3.44 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 56 | 2.86 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 12 | 3.55 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 72 | 2.75 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 58 | 1.70 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 8 | 3.62 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 68 | 1.84 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 40 | 2.91 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 60 | 1.79 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 44 | 2.91 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 36 | 2.93 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 4 | 3.98 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 48 | 2.90 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 32 | 3.09 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Baseline | 4.10 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 50 | 0.83 Log10 IU/mL |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Hepatitis B Surface Antigen (HBsAg) Level | Week 28 | 3.10 Log10 IU/mL |
Secondary
Part 3: Percentage of Participants With AEs
Time frame: 72 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Percentage of Participants With AEs | 68.8 Percentage of Participants |
| Part 1a: SAD Cohort 1 | Part 3: Percentage of Participants With AEs | 90 Percentage of Participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Percentage of Participants With AEs | 100 Percentage of Participants |
Secondary
Part 3: Percentage of Participants With Anti-Hepatitis B Core Antigen (HBc) Antibodies
Time frame: Up to Week 72
Population: This endpoint included participants from Part 3 who were anti-HBc+ at baseline.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Percentage of Participants With Anti-Hepatitis B Core Antigen (HBc) Antibodies | 100 Percentage of participants |
| Part 1a: SAD Cohort 1 | Part 3: Percentage of Participants With Anti-Hepatitis B Core Antigen (HBc) Antibodies | 100 Percentage of participants |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Percentage of Participants With Anti-Hepatitis B Core Antigen (HBc) Antibodies | 100 Percentage of participants |
Secondary
Part 3: T1/2 of RO7049389
Time frame: Day 1 - Week 48
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: T1/2 of RO7049389 | Week 48 | 4.05 Hours |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: T1/2 of RO7049389 | Week 24 | 1.30 Hours |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: T1/2 of RO7049389 | Day 1 | 1.16 Hours |
| Part 1a: SAD Cohort 1 | Part 3: T1/2 of RO7049389 | Week 24 | 1.43 Hours |
| Part 1a: SAD Cohort 1 | Part 3: T1/2 of RO7049389 | Day 1 | 1.13 Hours |
| Part 1a: SAD Cohort 1 | Part 3: T1/2 of RO7049389 | Week 4 | 1.38 Hours |
| Part 1a: SAD Cohort 1 | Part 3: T1/2 of RO7049389 | Week 48 | 3.40 Hours |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: T1/2 of RO7049389 | Day 1 | 1.31 Hours |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: T1/2 of RO7049389 | Week 48 | 3.98 Hours |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: T1/2 of RO7049389 | Week 24 | 1.38 Hours |
Secondary
Part 3: Tmax of RO7049389
Time frame: Day 1 - Week 48
Population: The pharmacokinetic population included all participants unless they significantly violated inclusion/exclusion criteria, deviated significantly from the protocol, or if they had unavailable or incomplete data that could affect analysis.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Tmax of RO7049389 | Day 1 | 1.99 Hours |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Tmax of RO7049389 | Week 48 | 1.02 Hours |
| Parts 1a and 1b: Single Ascending Dose (SAD) Placebo | Part 3: Tmax of RO7049389 | Week 24 | 1.94 Hours |
| Part 1a: SAD Cohort 1 | Part 3: Tmax of RO7049389 | Week 24 | 2.00 Hours |
| Part 1a: SAD Cohort 1 | Part 3: Tmax of RO7049389 | Day 1 | 2.00 Hours |
| Part 1a: SAD Cohort 1 | Part 3: Tmax of RO7049389 | Week 48 | 2.50 Hours |
| Part 1a: SAD Cohort 1 | Part 3: Tmax of RO7049389 | Week 4 | 2.02 Hours |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Tmax of RO7049389 | Week 48 | 2.00 Hours |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Tmax of RO7049389 | Day 1 | 1.96 Hours |
| Part 1a and Part 1b: SAD Cohort 2 (Food Effect) | Part 3: Tmax of RO7049389 | Week 24 | 2.00 Hours |