A Study to Investigate the Safety, Tolerability, Pharmaco... | NCT02952924

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Parts 1a and 1b: SAD in Healthy Volunteers (Placebo)	Placebo Comparator	In Part 1a, participants will receive a single oral dose of placebo matching to RO7049389 film coated tablet on Day 1. In Part 1b, minimum 8 participants from Part 1a will be selected and 2 of whom will receive another single dose of placebo matching to RO7049389 on Day 16 after eating the standard United States - Food and Drug Administration (US FDA)-recommended high-fat and high-calorie breakfast.	Other: Placebo
Parts 1a and 1b: SAD in Healthy Volunteers (RO7049389)	Experimental	In Part 1a, participants will receive a single oral dose of RO7049389 film coated tablet on Day 1 in dose-escalation cohorts with a starting dose of 150 milligrams (mg). The doses for subsequent cohorts will be defined by an adaptive approach based on the safety and PK data in previously-dosed healthy volunteers. In Part 1b, minimum 8 participants from Part 1a will be selected and 6 of whom will receive another single dose of RO7049389 on Day 16 after eating the standard US FDA-recommended high-fat and high-calorie breakfast.	Drug: RO7049389
Part 1c: MAD in Healthy Volunteers (Placebo)	Placebo Comparator	Participants will receive placebo matching to RO7049389 film coated tablet from Days 1 to 13 (either once a day [QD] or twice a day [BID]) and a single dose of placebo matching to RO7049389 film coated tablet in the morning of Day 14. Participants will also receive a single dose of midazolam solution (100 micrograms [mcg]) on Day -1 and Day 14.	Drug: Midazolam Other: Placebo
Part 1c: MAD in Healthy Volunteers (RO7049389)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Midazolam	Drug	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	Part 1c: MAD in Healthy Volunteers (Placebo)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Royal Brisbane and Women's Hospital		Herston	Queensland	4029	Australia
Royal Melbourne Hospital

PubMed Identifier	Type	Citation	Retractions
34237271	Derived	Yuen MF, Zhou X, Gane E, Schwabe C, Tanwandee T, Feng S, Jin Y, Triyatni M, Lemenuel-Diot A, Cosson V, Xue Z, Kazma R, Bo Q. Safety, pharmacokinetics, and antiviral activity of RO7049389, a core protein allosteric modulator, in patients with chronic hepatitis B virus infection: a multicentre, randomised, placebo-controlled, phase 1 trial. Lancet Gastroenterol Hepatol. 2021 Sep;6(9):723-732. doi: 10.1016/S2468-1253(21)00176-X. Epub 2021 Jul 6.
32839221

ID	Title	Description
FG000	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.
FG001	Part 1c: Multiple Ascending Dose (MAD) Placebo

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	May 21, 2020

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	Part 1a: SAD Cohort 1	HVs received a single dose of 150 mg of RO7049389 under fasted conditions.
BG004	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.
BG005	Part 1a: SAD Cohort 3	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.
BG006	Part 1a: SAD Cohort 4	HVs received a single dose of 2000 mg of RO7049389 under fasted conditions.
BG007	Part 1a: SAD Cohort 5	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.
BG008	Part 1a: SAD Cohort 6	HVs received a single dose of 2500 mg of RO7049389 under fasted conditions.
BG009	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.
BG010	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.
BG011	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.
BG012	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.
BG013	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.
BG014	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.
BG015	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.
BG016	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.
BG017	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.
BG018	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.
BG019	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.
BG020	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.
BG021	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.
BG022	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Part 1: Percentage of Participants With Adverse Events

The safety analysis population included all participants who received at least one dose of study drug, whether prematurely withdrawn from the study or not.

Posted

Number

Percentage of participants

Up to Day 29 (Part 1a), Day 44 (Part 1b), Day 42 (Part 1c)

ID	Title	Description
OG000	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.
OG001	Part 1a: SAD Cohort 1	HVs received a single dose of 150 mg of RO7049389 under fasted conditions.
OG002	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.
OG003	Part 1a: SAD Cohort 3	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.
OG004	Part 1a: SAD Cohort 4	HVs received a single dose of 2000 mg of RO7049389 under fasted conditions.
OG005	Part 1a: SAD Cohort 5	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.
OG006	Part 1a: SAD Cohort 6	HVs received a single dose of 2500 mg of RO7049389 under fasted conditions.
OG007	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.
OG008	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.
OG009	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.
OG010	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.
OG011	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.
OG012	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.

Units	Counts
Participants	OG00011 OG0013 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
	OG00027.3 OG00133.3 OG00250.0 OG003

Primary

Parts 1a and 1b: SAD Cohort: Time to Reach Maximum Concentration (Tmax) of RO7049389

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.

Posted

Median

Full Range

Hours

Up to 28 days

ID	Title	Description
OG000	Part 1a: SAD Cohort 1	HVs received a single dose of 150 mg of RO7049389 under fasted conditions.
OG001	Part 1a : SAD Cohort 2 (Food Effect - Fasted)	Part 1a: Single oral dose of 450 mg of RO7049389 under fasted conditions.
OG002	Part 1b: SAD Cohort 2 (Food Effect - Fed)	Part 1b: Single oral dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal.
OG003	Part 1a: SAD Cohort 3	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Primary

Parts 1a and 1b: SAD Cohort: Maximum Observed Plasma Concentration (Cmax) of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Up to 28 days

ID	Title	Description
OG000	Part 1a: SAD Cohort 1	HVs received a single dose of 150 mg of RO7049389 under fasted conditions.
OG001	Part 1a : SAD Cohort 2 (Food Effect - Fasted)	Part 1a: Single oral dose of 450 mg of RO7049389 under fasted conditions.
OG002	Part 1b: SAD Cohort 2 (Food Effect - Fed)	Part 1b: Single oral dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal.
OG003	Part 1a: SAD Cohort 3	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Primary

Parts 1a and 1b: SAD Cohort: AUC From Time Zero to Infinity (AUC0-inf) of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*hr/mL

Up to 28 days

ID	Title	Description
OG000	Part 1a: SAD Cohort 1	HVs received a single dose of 150 mg of RO7049389 under fasted conditions.
OG001	Part 1a : SAD Cohort 2 (Food Effect - Fasted)	Part 1a: Single oral dose of 450 mg of RO7049389 under fasted conditions.
OG002	Part 1b: SAD Cohort 2 (Food Effect - Fed)	Part 1b: Single oral dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal.
OG003	Part 1a: SAD Cohort 3	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Primary

Parts 1a and 1b: SAD Cohort: Area Under the Curve From Time Zero to the Last Measurable Concentration (AUC0-last) of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*hr/mL

Up to 28 days

ID	Title	Description
OG000	Part 1a: SAD Cohort 1	HVs received a single dose of 150 mg of RO7049389 under fasted conditions.
OG001	Part 1a : SAD Cohort 2 (Food Effect - Fasted)	Part 1a: Single oral dose of 450 mg of RO7049389 under fasted conditions.
OG002	Part 1b: SAD Cohort 2 (Food Effect - Fed)	Part 1b: Single oral dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal.
OG003	Part 1a: SAD Cohort 3	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Primary

Parts 1a and 1b: SAD Cohort: Half-life (T1/2) of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Up to Day 28

ID	Title	Description
OG000	Part 1a: SAD Cohort 1	HVs received a single dose of 150 mg of RO7049389 under fasted conditions.
OG001	Part 1a : SAD Cohort 2 (Food Effect - Fasted)	Part 1a: Single oral dose of 450 mg of RO7049389 under fasted conditions.
OG002	Part 1b: SAD Cohort 2 (Food Effect - Fed)	Part 1b: Single oral dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal.
OG003	Part 1a: SAD Cohort 3	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Primary

Parts 1a and 1b: SAD Cohort: Apparent Oral Clearance (CL/F) of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

L/hr

Up to Day 28

ID	Title	Description
OG000	Part 1a: SAD Cohort 1	HVs received a single dose of 150 mg of RO7049389 under fasted conditions.
OG001	Part 1a : SAD Cohort 2 (Food Effect - Fasted)	Part 1a: Single oral dose of 450 mg of RO7049389 under fasted conditions.
OG002	Part 1b: SAD Cohort 2 (Food Effect - Fed)	Part 1b: Single oral dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal.
OG003	Part 1a: SAD Cohort 3	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Primary

Parts 1a and 1b: SAD Cohort: Cumulative Amount Excreted Unchanged in Urine (Ae) of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

Up to Day 28

ID	Title	Description
OG000	Part 1a: SAD Cohort 1	HVs received a single dose of 150 mg of RO7049389 under fasted conditions.
OG001	Part 1a : SAD Cohort 2 (Food Effect - Fasted)	Part 1a: Single oral dose of 450 mg of RO7049389 under fasted conditions.
OG002	Part 1b: SAD Cohort 2 (Food Effect - Fed)	Part 1b: Single oral dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal.
OG003	Part 1a: SAD Cohort 3	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Primary

Parts 1a and 1b: SAD Cohort: Renal Clearance (CLr) of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

mL/min

Up to Day 28

ID	Title	Description
OG000	Part 1a: SAD Cohort 1	HVs received a single dose of 150 mg of RO7049389 under fasted conditions.
OG001	Part 1a: SAD Cohort 2 (Food Effect - Fasted)	Part 1a: Single oral dose of 450 mg of RO7049389 under fasted conditions.
OG002	Part 1b: SAD Cohort 2 (Food Effect - Fed)	Part 1b: Single oral dose of 450 mg of RO7049389 on Day 16 after a standard US FDA-recommended high-fat high-calorie meal.
OG003	Part 1a: SAD Cohort 3	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.

Primary

Part 2: Percentage of Participants With Adverse Events

The safety analysis population included all participants who received at least one dose of study drug, whether prematurely withdrawn from the study or not.

Posted

Number

Percentage of participants

Up to Day 112

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.

Primary

Part 2: Quantitative Plasma HBV DNA Level

The efficacy population included all participants who received at least one dose of RO7049389.

Posted

Median

Full Range

Log10 IU/mL

Baseline - Day 112

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.

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.

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.

Posted

Number

95% Confidence Interval

Percentage

Every 2-4 weeks from Baseline through Week 72

ID	Title	Description
OG000	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.
OG001	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.
OG002	Part 3: Cohort C

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.

Posted

Geometric Mean

90% Confidence Interval

geometric mean ratio

Day 16

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Part 1b: Food Effect on AUCinf of RO7049389

Posted

Geometric Mean

90% Confidence Interval

geometric mean ratio

Day 16

ID	Title	Description
OG000	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.

Units	Counts
Participants	OG000

Secondary

Part 1c: Cmax of Midazolam

This endpoint presents the geometric mean ratio (after RO7049389/before RO7049389).

Posted

Geometric Mean

90% Confidence Interval

Ratio

Up to Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 1c: AUCinf of Midazolam

This endpoint presents the geometric mean ratio (after RO7049389/before RO7049389).

Posted

Geometric Mean

90% Confidence Interval

Ratio

Up to Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 1c: Tmax of RO7049389

Posted

Median

Full Range

hours

Up to Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	Part 1c: MAD Cohort 4

Secondary

Part 1c: Cmax of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Up to Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003

Secondary

Part 1c: AUC0-12hr of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*hr/mL

Up to Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003

Secondary

Part 1c: CLr of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

mL/min

Up to Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Geometric mean ratio

Day 1, Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 1c: T1/2 of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Up to Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003

Secondary

Part 1c: Ae of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

Up to Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003

Secondary

Part 1c: Ctrough of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Up to Day 14

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 2: HBV DNA < Lower Limit of Quantification (LLOQ)

The efficacy population included all participants who received at least one dose of RO7049389.

Posted

Number

Percentage of participants

Baseline - Day 112/Follow-up Day 84

ID	Title	Description
OG000	Part 2: 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.
OG001	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.
OG002	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.
OG003	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.

Secondary

Part 2: Tmax of RO7049389

Posted

Median

Full Range

Hours

Up to Day 28

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.

Secondary

Part 2: Cmax of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Up to Day 28

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.

Secondary

Part 2: AUCtau of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

ng*hr/mL

Up to Day 28

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.

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.

Posted

Geometric Mean

Geometric Coefficient of Variation

Geometric mean ratio

Day 1, Day 28

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 2: T1/2 of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

Hours

Up to Day 28

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.

Secondary

Part 2: Ctrough of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Up to Day 28

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.
OG003	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.

Secondary

Part 3: Percentage of Participants With AEs

Posted

Number

Percentage of Participants

72 weeks

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: Hepatitis B Surface Antigen (HBsAg) Level

Posted

Median

Full Range

Log10 IU/mL

Baseline - Week 72

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: Hepatitis B e-Antigen (HBeAg) Levels

The population for this endpoint included participants in Part 3 that were HBeAg+ at baseline.

Posted

Median

Full Range

Log10 IU/mL

Baseline - Week 72

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: HBV RNA Level

Posted

Median

Full Range

Log10 copies/mL

Baseline - Week 72

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: HBV Core-Related Antigen (HBcrAg) Levels

Posted

Median

Full Range

Log10 U/mL

Baseline - Week 72

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: Alanine Transaminase (ALT) Normalization in Participants With Baseline ALT Elevation

This endpoint includes participants from Part 3 with elevated ALT at baseline.

Posted

Number

Percentage of participants

Week 12 - Week 72

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: Percentage of Participants With Anti-Hepatitis B Core Antigen (HBc) Antibodies

This endpoint included participants from Part 3 who were anti-HBc+ at baseline.

Posted

Number

Percentage of participants

Up to Week 72

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: HBV DNA Level

Posted

Median

Full Range

Log10 copies/mL

Baseline - Week 72

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: HBV DNA < Lower Limit of Quantification (LLOQ)

Posted

Number

Percentage of participants

Baseline - Week 72

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: Tmax of RO7049389

Posted

Median

Full Range

Hours

Day 1 - Week 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: Cmax of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

ng/mL

Day 1 - Week 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: AUCtau of RO7049389

Posted

Geometric Mean

Geometric Coefficient of Variation

h*ng/mL

Day 1 - Week 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Secondary

Part 3: T1/2 of RO7049389

Posted

Median

Full Range

Hours

Day 1 - Week 48

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	0	11	0	11	3	11
EG001	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.	0	10	0	10	6	10
EG002	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.	0	6	1	6	3	6
EG003	Part 1a: SAD Cohort 1	HVs received a single dose of 150 mg of RO7049389 under fasted conditions.	0	3	0	3	1	3
EG004	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.	0	6	0	6	3	6
EG005	Part 1a: SAD Cohort 3	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.	0	3	0	3	3	3
EG006	Part 1a: SAD Cohort 4	HVs received a single dose of 2000 mg of RO7049389 under fasted conditions.	0	6	0	6	5	6
EG007	Part 1a: SAD Cohort 5	HVs received a single dose of 1000 mg of RO7049389 under fasted conditions.	0	6	0	6	2	6
EG008	Part 1a: SAD Cohort 6	HVs received a single dose of 2500 mg of RO7049389 under fasted conditions.	0	6	0	6	3	6
EG009	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.	0	6	0	6	5	6
EG010	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.	0	7	0	7	4	7
EG011	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.	0	7	0	7	2	7
EG012	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.	0	6	0	6	1	6
EG013	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.	0	6	0	6	1	6
EG014	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.	0	6	0	6	4	6
EG015	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.	0	6	0	6	4	6
EG016	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.	0	6	0	6	5	6
EG017	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.	0	7	0	7	4	7
EG018	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.	0	6	0	6	2	6
EG019	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.	0	32	1	32	22	32
EG020	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.	1	10	1	10	9	10
EG021	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.	0	30	2	30	30	30

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Lymphadenitis	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG0030 events0 affected3 at risk EG0040 events0 affected6 at risk EG0050 events0 affected3 at risk EG0060 events0 affected6 at risk EG0070 events0 affected6 at risk EG0080 events0 affected6 at risk EG0090 events0 affected6 at risk EG0100 events0 affected7 at risk EG0110 events0 affected7 at risk EG0120 events0 affected6 at risk EG0130 events0 affected6 at risk EG0140 events0 affected6 at risk EG0150 events0 affected6 at risk EG0160 events0 affected6 at risk EG0170 events0 affected7 at risk EG0180 events0 affected6 at risk EG0190 events0 affected32 at risk EG0201 events1 affected10 at risk EG0210 events0 affected30 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Cellulitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Liver function test increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0021 events1 affected6 at risk EG003
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG0030 events0 affected3 at risk EG0040 events0 affected6 at risk EG0050 events0 affected3 at risk EG0060 events0 affected6 at risk EG0070 events0 affected6 at risk EG0080 events0 affected6 at risk EG0090 events0 affected6 at risk EG0100 events0 affected7 at risk EG0110 events0 affected7 at risk EG0120 events0 affected6 at risk EG0130 events0 affected6 at risk EG0140 events0 affected6 at risk EG0150 events0 affected6 at risk EG0160 events0 affected6 at risk EG0170 events0 affected7 at risk EG0180 events0 affected6 at risk EG0190 events0 affected32 at risk EG0200 events0 affected10 at risk EG0212 events2 affected30 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Splenomegaly	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Palpitations	Cardiac disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Deafness	Ear and labyrinth disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Motion sickness	Ear and labyrinth disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Thyroid disorder	Endocrine disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Thyroid mass	Endocrine disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Blepharitis	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Blepharospasm	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Conjunctival haemorrhage	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Conjunctivitis allergic	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Orbital oedema	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Visual impairment	Eye disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Abdominal discomfort	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Abdominal distension	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Dental caries	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Epigastric discomfort	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected10 at risk EG0020 events0 affected6 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Haemorrhoids	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Toothache	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Catheter site bruise	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Catheter site erythema	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected10 at risk EG0020 events0 affected6 at risk EG003
Catheter site pain	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Catheter site swelling	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected10 at risk EG0020 events0 affected6 at risk EG003
Chest discomfort	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Fatigue	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Influenza like illness	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0021 events1 affected6 at risk EG003
Injection site erythema	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Malaise	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Medical device site dermatitis	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Medical device site rash	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Pain	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Pyrexia	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Swelling face	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Vessel puncture site haematoma	General disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Hepatic steatosis	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Hepatitis	Hepatobiliary disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
COVID-19	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Mumps	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Periorbital cellulitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Respiratory tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Rhinitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0021 events1 affected6 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0021 events1 affected6 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Vaginal infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0021 events1 affected6 at risk EG003
Viral infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Dental restoration failure	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Muscle strain	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Thermal burn	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Tooth fracture	Injury, poisoning and procedural complications	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Blood triglycerides increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Haemoglobin decreased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Platelet count decreased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Weight decreased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
White blood cell count decreased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Hyperlipidaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Increased appetite	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Limb discomfort	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0012 events1 affected10 at risk EG0020 events0 affected6 at risk EG003
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Dizziness	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Headache	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0003 events2 affected11 at risk EG0013 events2 affected10 at risk EG0021 events1 affected6 at risk EG003
Hypoaesthesia	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Lethargy	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Lumbosacral radiculopathy	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Presyncope	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected10 at risk EG0020 events0 affected6 at risk EG003
Heavy menstrual bleeding	Reproductive system and breast disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Intermenstrual bleeding	Reproductive system and breast disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Menstrual disorder	Reproductive system and breast disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Dry throat	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Blister	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Petechiae	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0011 events1 affected10 at risk EG0020 events0 affected6 at risk EG003
Rash vesicular	Skin and subcutaneous tissue disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003
Lymphadenitis	Blood and lymphatic system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected11 at risk EG0010 events0 affected10 at risk EG0020 events0 affected6 at risk EG003

ID	Term
D006509	Hepatitis B
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D018347	Hepadnaviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D006525	Hepatitis, Viral, Human
D006521	Hepatitis, Chronic
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases
D002908	Chronic Disease
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms

ID	Term
D001569	Benzodiazepines
D001552	Benzazepines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds