A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7049389 in Healthy Volunteers and Chronic Hepatitis B Virus (HBV) Infected Participants

Hepatitis B, Chronic Clinical Trial

Official title:

A Safety, Tolerability, Pharmacokinetics and Efficacy Study of ro7049389 in: (1) Single- (With or Without Food) and Multiple- (With Midazolam) Ascending Doses in Healthy Volunteers; (2) Patients Chronically Infected With Hepatitis b Virus (3) Patients With Chronic Hepatitis B.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02952924
• Other study ID #: YP39364
• Status: Completed
• Phase: Phase 1
• Start date: December 14, 2016
• Est. completion date: March 16, 2022

Study information

• Verified date: July 2022
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 192
• Est. completion date: March 16, 2022
• Est. primary completion date: March 16, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic

Intervention

Drug:
• Midazolam
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

Other:
• Placebo
Placebo matching to RO7049389 will be administered as per schedule described in individual arm.

Drug:
• RO7049389
RO7049389 will be administered as per schedule described in individual arm.

Locations

Country	Name	City	State
Australia	Royal Brisbane and Women's Hospital	Herston	Queensland
Australia	Royal Melbourne Hospital	Parkville	Victoria
Bulgaria	Acibadem City Clinic Tokuda Hospital Ead	Sofia
China	Nanfang Hospital, Southern Medical University	Guangzhou
China	Shanghai Jiao Tong University School of Medicine (SJTUSM) - Ruijin Hospital (GuangCi Hospital)	Shanghai
China	Huashan Hospital Affiliated to Fudan University	Shanghai City
Hong Kong	The University of Hong Kong; Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Shatin, New Territories
New Zealand	Middlemore Hospital	Auckland
New Zealand	Auckland Clinical Studies Limited	Grafton
Singapore	National University Health System	Singapore
Singapore	Singapore General Hospital	Singapore
Taiwan	Chang Gung Memorial Hospital - Kaohsiung Branch	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung City
Taiwan	Taichung Veterans Gen Hosp	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Chang Gung Memorial Hospital - Linkou Branch	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei City
Thailand	King Chulalongkorn Memorial Hospital	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	Maharaj Nakorn Chiang Mai Hospital	Chiang Mai

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Australia,  Bulgaria,  China,  Hong Kong,  New Zealand,  Singapore,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Percentage of Participants With Adverse Events		From randomization up to Day 44
Primary	Part 2: Percentage of Participants With Adverse Events		From randomization up to Day 56
Primary	Part 2: HBV DNA Level		Baseline; Days 8, 15, 22, 28, 35, 56, 84, and 112
Primary	Part 1c- MAD Cohort: Area Under the Plasma Concentration Versus Time Curve for a Dosing Interval (AUC0-tau) of RO7049389 and Metabolites		Pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hrs post Day 1 morning dose; pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post Day 14 morning dose
Primary	Part 1c- MAD Cohort: Plasma Trough Concentration (Ctrough) of RO7049389 and Metabolites		Pre-dose (0 hr before morning dose) on Days 2, 3, 4, 5, 7
Primary	Part 1c- MAD Cohort: Apparent Terminal t1/2 of RO7049389 and Metabolites		Pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hrs post Day 1 morning dose; pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post Day 14 morning dose
Primary	Part 1c- MAD Cohort: Accumulation Index of RO7049389 and Metabolites		Pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hrs post Day 1 morning dose; pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post Day 14 morning dose
Primary	Part 1c- MAD Cohort: Ae of RO7049389 and Metabolites		Pre-dose (0 hr), 0-4, 4-8, 8-12, 12-24 hours post morning dose on Days 1 and 14
Primary	Part 1c- MAD Cohort: CLR of RO7049389 and Metabolites		Pre-dose (0 hr), 0-4, 4-8, 8-12, 12-24 hours post morning dose on Days 1 and 14
Primary	Part 1a- SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389 and Metabolites		Pre-dose (0 hour [hr]) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose
Primary	Part 1a- SAD Cohort: Time to Reach Cmax (Tmax) of RO7049389 and Metabolites		Pre-dose (0 hr) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose
Primary	Part 1a- SAD Cohort: Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUC0-last) of RO7049389 and Metabolites		Pre-dose (0 hr) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose
Primary	Part 1a- SAD Cohort: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUC0-inf) of RO7049389 and Metabolites		Pre-dose (0 hr) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose
Primary	Part 1a- SAD Cohort: Apparent Terminal Half-life (t1/2) of RO7049389 and Metabolites		Pre-dose (0 hr) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose
Primary	Part 1a- SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389 and Metabolites		Pre-dose (0 hr) on Day 1; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 1 dose
Primary	Part 1a-SAD Cohort- Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389 and Metabolites		Pre-dose (0 hr) on Day 1; 0-4, 4-8, 8-12, 12-24, 24-48 hours post Day 1 dose
Primary	Part 1a- SAD Cohort: Renal Clearance (CLR) of RO7049389 and Metabolites		Pre-dose (0 hr) on Day 1; 0-4, 4-8, 8-12, 12-24, 24-48 hours post Day 1 dose
Primary	Part 1c- MAD Cohort: Cmax of RO7049389 and Metabolites		Pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hrs post Day 1 morning dose; pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post Day 14 morning dose
Primary	Part 1c- MAD Cohort: Tmax of RO7049389 and Metabolites		Pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 hrs post Day 1 morning dose; pre-dose (0 hr) and 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, and 48 hrs post Day 14 morning dose
Primary	Part 3 HBV DNA Level		Every 2-4 weeks from Baseline through Week 72
Primary	Part 3: HBsAg Level		Every 2-4 weeks from baseline through week 72
Secondary	Part 1b- Food-Effect SAD Cohort: Cmax of RO7049389		Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose
Secondary	Part 1b- Food-Effect SAD Cohort: Tmax of RO7049389		Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose
Secondary	Part 1b- Food-Effect SAD Cohort: AUC0-last of RO7049389		Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose
Secondary	Part 1b- Food-Effect SAD Cohort: AUC0-inf of RO7049389		Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose
Secondary	Part 1b- Food-Effect SAD Cohort: Apparent Terminal t1/2 of RO7049389		Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose
Secondary	Part 1b- Food-Effect SAD Cohort: Apparent CL/F of RO7049389		Pre-dose (0 hr) on Day 16; 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48, 72 and 96 hrs post Day 16 dose
Secondary	Part 1c- MAD Cohort: Cmax of Midazolam		Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14
Secondary	Part 1c- MAD Cohort: Tmax of Midazolam		Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14
Secondary	Part 1c- MAD Cohort: AUC0-last of Midazolam		Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14
Secondary	Part 1c- MAD Cohort: AUC0-inf of Midazolam		Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14
Secondary	Part 1c- MAD Cohort: Area Under the Plasma Concentration Versus Time Curve up to 6 h Post-dose (AUC0-6h) of Midazolam		Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14
Secondary	Part 1c- MAD Cohort: Apparent Terminal t1/2 of Midazolam		Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14
Secondary	Part 1c- MAD Cohort: CL/F of Midazolam		Pre-dose (0 hr), 0.25, 0.5,1, 2, 4, 6, 8, 10, and 12 hrs post-midazolam dose on Day -1; pre-RO7049389 dose (0 hr) on Day 1; pre-dose (0 hr), 0.25, 0.5, 1, 2, 4, 6, 8, 10, 12, and 24 hrs post-midazolam dose on Day 14
Secondary	Part 2: Cmax of RO7049389		Pre-dose (0 hr) and 1, 2, 3, 4, 6, and 8 hrs post Day 1 morning dose; pre-dose (0 hr) and 1, 2, 3, 4, 6, 8, and 24 hrs post Day 28 morning dose
Secondary	Part 2: Tmax of RO7049389		Pre-dose (0 hr) and 1, 2, 3, 4, 6, and 8 hrs post Day 1 morning dose; pre-dose (0 hr) and 1, 2, 3, 4, 6, 8, and 24 hrs post Day 28 morning dose
Secondary	Part 2: AUC0-tau of RO7049389		Pre-dose (0 hr) and 1, 2, 3, 4, 6, and 8 hrs post Day 1 morning dose; pre-dose (0 hr) and 1, 2, 3, 4, 6, 8, and 24 hrs post Day 28 morning dose
Secondary	Part 2: Ctrough of RO7049389		Pre-morning dose (0 hr) on Days 2, 3, 4, 8, 15, 22
Secondary	Part 2: Apparent t1/2 of RO7049389		Pre-dose (0 hr) and 1, 2, 3, 4, 6, and 8 hrs post Day 1 morning dose; pre-dose (0 hr) and 1, 2, 3, 4, 6, 8, and 24 hrs post Day 28 morning dose
Secondary	Part 2: Accumulation Index of RO7049389		Pre-dose (0 hr) and 1, 2, 3, 4, 6, and 8 hrs post Day 1 morning dose; pre-dose (0 hr) and 1, 2, 3, 4, 6, 8, and 24 hrs post Day 28 morning dose
Secondary	Part 2: Anti-HBe Antibodies		Baseline; Days 8,15,22,28,35,56,84, and 112
Secondary	Part 3: Cmax of RO7049389 and its Metabolites		Pre-dose and 1,2,3,4,6, and 8 hours post-dose (Day 1, Week 4 (Cohort B only) and Week 24); pre-dose and 1,2,3,4,6,8, and 24 hours after the last dose (Week 48)
Secondary	Part 3: Tmax of RO7049389 and its metabolites		Pre-dose and 1,2,3,4,6, and 8 hours post-dose (Day 1, Week 4 (Cohort B only) and Week 24); pre-dose and 1,2,3,4,6,8, and 24 hours after the last dose (Week 48)
Secondary	Part 3: AUC0-tau of RO7049389 and its metabolites		Pre-dose and 1,2,3,4,6, and 8 hours post-dose (Day 1, Week 4 (Cohort B only) and Week 24); pre-dose and 1,2,3,4,6,8, and 24 hours after the last dose (Week 48)
Secondary	Part 3: Ctrough of RO7049389 and its metabolites		Pre-dose Days 14 and 28; thereafter predose every 28 days up to Week 48
Secondary	Part 3: T1/2 of RO7049389 and its metabolites		Pre-dose and 1,2,3,4,6, and 8 hours post-dose (Day 1, Week 4 (Cohort B only) and Week 24); pre-dose and 1,2,3,4,6,8, and 24 hours after the last dose (Week 48)
Secondary	Part 3: Accumulation Index of RO7049389 and its Metabolites		Pre-dose and 1,2,3,4,6, and 8 hours post-dose (Day 1, Week 4 (Cohort B only) and Week 24); pre-dose and 1,2,3,4,6,8, and 24 hours after the last dose (Week 48)
Secondary	Part 3: Ctrough of Nucleos(t)ide Analogs (NUCs)		Pre-dose Days 14 (Cohort A and C only) and 28; thereafter predose every 28 days up to Week 48
Secondary	Part 3: Hepatitis B e-Antigen (HBeAg) Levels		Every 2-4 weeks from Baseline through Week 72
Secondary	Part 3: Anti-HBs Antibodies		Every 2-4 weeks from Baseline through Week 72
Secondary	Part 3: Anti-HBe Antibodies		Every 2-4 weeks from Baseline through Week 72
Secondary	Part 3: Anti-HBc antibodies		Every 2-4 weeks from Baseline through Week 72
Secondary	Part 3: HBV RNA Level		Every 2-4 weeks from Baseline through Week 72
Secondary	Part 3: HBV Core-Related Antigen Levels (HBcrAg)		Every 2-4 weeks from baseline through week 72
Secondary	Part 3: Viral Resistance Monitoring		Every 2-4 weeks from baseline through week 72
Secondary	Part 3 Percentage of Participants With Adverse Events		From randomization up to 72 Weeks