A Double-Blind Single-Ascending Dose (SAD) and Multiple-Ascending Dose (MAD) Study to Investigate the Safety, Tolerability, and Pharmacokinetics of RO7049389 in Healthy Chinese Participants

Study Overview
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Brief Summary
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This study will assess the safety and tolerability of RO7049389 compared to placebo in single- and multiple-ascending doses in healthy Chinese participants.

Official Title
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A Randomized, Sponsor-Open, Investigator-Blinded, Subject-Blinded, Placebo-Controlled, Single-Ascending Dose (SAD) and Multiple-Ascending Dose (MAD) Study to Investigate the Safety, Tolerability, and Pharmacokinetics of RO7049389 in Healthy Chinese Subjects

Conditions
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Hepatitis B Virus

Intervention / Treatment
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* Drug: RO7049389
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Chinese healthy male and female subjects, 18 to 60 years of age, inclusive. A Body Mass Index (BMI) of between 19 to 27 kg/m2 inclusive, and a body weight of at least 45 kg. Women should be of non-childbearing potential. Female subjects must be either surgically sterile (by means of hysterectomy and/or bilateral oophorectomy) or post-menopausal for at least one year (defined as amenorrhea >/=12 consecutive months without another cause, and confirmed by follicle stimulating hormone level >35 mIU/mL). For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm Exclusion Criteria Pregnant (positive pregnancy test) or lactating women, and male subjects with partners who are pregnant or lactating. 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. Personal history of congenital long QT syndrome or family history of sudden death. History of Gilbert's syndrome. History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral or inhaled corticosteroids) </=6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study. Subjects 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 (non-active hay fever is acceptable). Electrocardiogram (ECG) with QRS and/or T-wave judged to be unfavorable for a consistently accurate QT measurement (e.g., neuromuscular artifact that cannot be readily eliminated, arrhythmias, indistinct QTS onset, low amplitude T-wave, merged T- and U waves, prominent U-waves) Creatinine clearance (CrCl) </=70 mL/min (using the Cockcroft-Gault formula) 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 1 and 2 (HIV Ab). Participation in an investigational drug or device study within 90 days prior to screening or more than 4 times per year. Donation or loss of blood over 500 mL within 3 months prior to screening. Any suspicion or history of drug and/or alcohol abuse within the last year. History (within 3 months of screening) of alcohol consumption exceeding two standard drinks per day on average (1 standard drink = 10 grams of alcohol). Alcohol consumption will be prohibited at least 48 hours before screening, 48 hours before and 48 hours after each dose, and 48 hours before each scheduled visit. Use of >5 cigarettes or equivalent nicotine-containing product per day. Taking any prescribed or over-the-counter medications (including vitamins or herbal remedies) within 2 weeks of first dosing or within 5 times the elimination half-life of the medication prior to first dosing (whichever is longer). Occasional acetaminophen/paracetamol is allowed. Subjects under judicial supervision, guardianship or curatorship.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single-Ascending Dose (SAD)<br>Participants will receive a single dose of RO7049389. | Drug: RO7049389<br>* RO7049389 will be administered orally either as a single dose (SAD) or as multiple doses defined by the SAD portion of the study (MAD).<br>|
| Experimental: Multiple-Ascending Dose (MAD)<br>Participants will receive multiple doses of RO7049389. | Drug: RO7049389<br>* RO7049389 will be administered orally either as a single dose (SAD) or as multiple doses defined by the SAD portion of the study (MAD).<br>|
| Placebo Comparator: Placebo<br>Participants will receive either a single dose (SAD cohorts) or multiple doses (MAD cohorts) of placebo matched to RO7049389. | Drug: Placebo<br>* Placebo will be administered orally at a dose and frequency matched to RO7049389.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Adverse Events | An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. | From the date of first administered dose through 28 days after the last administered dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) of RO7049389 |  | At pre-defined intervals on Day 1 (SAD) and Day 14 (MAD) | 
| Time to Maximum Observed Plasma Concentration (Tmax) of RO7049389 |  | At pre-defined intervals on Day 1 (SAD) and Day 14 (MAD) | 
| Area Under the Plasma Concentration vs Time Curve to Last Measurable Concentration (AUClast) of RO7049389 |  | At pre-defined intervals on Day 1 (SAD) and Day 14 (MAD) | 
| Area Under the Plasma Concentration vs Time Curve Extrapolated to Infinity (AUC0-inf) |  | At pre-defined intervals on Day 1 (SAD) and Day 14 (MAD) | 
| Apparent Half-Life (T1/2) of RO7049389 |  | At pre-defined intervals on Day 1 (SAD) and Day 14 (MAD) | 
| Clearance (CL/F) of RO7049389 |  | At pre-defined intervals on Day 1 (SAD) | 
| Trough Plasma Concentration (Ctrough) of RO7049389 |  | At pre-defined intervals on Day 14 (MAD) | 
| Accumulation Index of RO7049389 |  | At pre-defined intervals on Day 14 (MAD) | 
| Area Under the Concentration vs Time Curve for a Dosing Interval (AUCtau) |  | At pre-defined intervals on Day 14 (MAD) |