A Study to Evaluate the Safety, Tolerability and Pharmacokinetics of RO7062931 in Healthy Chinese Volunteers.

Study Overview
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Brief Summary
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This randomized study will evaluate the safety, tolerability and pharmacokinetics of single ascending subcutaneously administered doses of RO7062931 in healthy volunteers.

Official Title
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A Randomized, Sponsor-Open, Investigator-Blind, Subject-Blind, Placebo-Controlled, Single Ascending Dose, to Investigate the Safety, Tolerability and Pharmacokinetics of RO7062931 Following Subcutaneously Administration in Healthy Chinese Volunteers

Conditions
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Healthy Participants

Intervention / Treatment
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* Drug: RO7062931
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chinese healthy male and female (of non-childbearing potential) volunteers. A Body Mass Index (BMI) between 19 to 27 kilogram per square meter (kg/m2) inclusive and a body weight of at least 45 kg. Women should be of non-childbearing potential. These include those who have undergone surgical sterilization (removal of ovaries and/or uterus) or are post-menopausal. Men must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures during treatment and up to 105 days after the last dose of RO7062931, and agree to refrain from donating sperm during this same period. Non-smoker (nor tobacco containing products) for at least 90 days prior to dosing on Day 1 and agree to remain as non-smoker during the study. Exclusion Criteria: History of drug or alcohol abuse or dependence in previous 6 months. Positive urine drug and alcohol screen or positive cotinine test at Screening or Day -1. Positive result on hepatitis B (HBV), hepatitis C (HCV), or human immunodeficiency virus (HIV)-1 and -2 at Screening. Confirmed blood pressure or resting pulse rate outside of accepted ranges. Participation in an investigational drug or device study within 90 days prior to screening. Donation of blood over 500 milliliters (mL) within three months prior to screening. Any major illness within the one month, or any febrile illness within two weeks preceding the screening visit. Alcohol consumption of more than 2 standard drinks per day on average. Screening or baseline ECG evidence of atrial fibrillation, atrial flutter, complete right or left bundle branch block, Wolff-Parkinson-White syndrome, or cardiac pacemaker. Any out of range findings in liver function tests, INR and renal function tests or any clinically significant abnormalities (as judged by the Investigator) in the physical examination and in the remaining laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis) at Screening or on Day-1.

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: RO7062931 0.3mg/kg<br>Participants will receive subcutaneously (SC) 0.3 milligram per kilogram (mg/kg) of RO7062931. | Drug: RO7062931<br>* RO7062931 will be administered SC in single ascending doses with starting of 0.3 mg/kg and subsequent doses of 1.0 mg/kg, 2.0 mg/kg and 3.0 mg/kg, respectively. Additional (optional) dose of 4.0 mg/kg may be administered based on safety, tolerability and PK data.<br>Drug: Placebo<br>* Matching placebo will be administered subcutaneously (SC).<br>|
| Experimental: RO7062931 1.0mg/kg<br>Participants will receive subcutaneously (SC) 1.0 milligram per kilogram (mg/kg) of RO7062931. | Drug: RO7062931<br>* RO7062931 will be administered SC in single ascending doses with starting of 0.3 mg/kg and subsequent doses of 1.0 mg/kg, 2.0 mg/kg and 3.0 mg/kg, respectively. Additional (optional) dose of 4.0 mg/kg may be administered based on safety, tolerability and PK data.<br>Drug: Placebo<br>* Matching placebo will be administered subcutaneously (SC).<br>|
| Experimental: RO7062931 2.0mg/kg<br>Participants will receive subcutaneously (SC) 2.0 milligram per kilogram (mg/kg) of RO7062931. | Drug: RO7062931<br>* RO7062931 will be administered SC in single ascending doses with starting of 0.3 mg/kg and subsequent doses of 1.0 mg/kg, 2.0 mg/kg and 3.0 mg/kg, respectively. Additional (optional) dose of 4.0 mg/kg may be administered based on safety, tolerability and PK data.<br>Drug: Placebo<br>* Matching placebo will be administered subcutaneously (SC).<br>|
| Experimental: RO7062931 4.0mg/kg<br>Participants will receive subcutaneously (SC) 4.0 milligram per kilogram (mg/kg) of RO7062931. | Drug: RO7062931<br>* RO7062931 will be administered SC in single ascending doses with starting of 0.3 mg/kg and subsequent doses of 1.0 mg/kg, 2.0 mg/kg and 3.0 mg/kg, respectively. Additional (optional) dose of 4.0 mg/kg may be administered based on safety, tolerability and PK data.<br>Drug: Placebo<br>* Matching placebo will be administered subcutaneously (SC).<br>|
| Placebo Comparator: Placebo<br>Participants will receive matching placebo. | Drug: Placebo<br>* Matching placebo will be administered subcutaneously (SC).<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 and AEs of Special Interest | Adverse events of special interest for this study include the following: Cases of an elevated ALT or AST in combination with either an elevated bilirubin or clinical jaundice Suspected transmission of an infectious agent by the study drug Severe injection site reactions Renal adverse events | Up to 16 weeks | 
| Percentage of Participants With Marked Laboratory Abnormalities Based on Hematology, Blood Chemistry, Coagulation and Urinalysis Test Results | Marked reference range has been predefined for each laboratory parameter. The marked reference range is broader than the standard reference range. Values falling outside the marked reference range that also represent a defined change from baseline will be considered marked laboratory abnormalities (i.e., potentially clinically relevant). If a baseline value is not available for a study subject, the midpoint of the standard reference range will be used as the study participant baseline value for the purposes of determining marked laboratory abnormalities. | Baseline, Day 2, 8, 15, 29, 85 | 
| Percentage of Participants With Electrocardiogram (ECG) Abnormalities | Table entries provide the percentage of Participants with a during treatment assessment abnormality in the direction specified regardless of this abnormality at baseline. Abnormalities reported in Participants with missing baseline values are included. Baseline is the Participant's last observation prior to initiation of study drug. | Baseline; pre-dose, 1 hour (h), 4, 8, 12h post-dose Day 1, 24h post-dose Day 2, 8, 15, 29, 85 | 
| Percentage of Participants With T-wave Abnormalities | Table entries provide the percentage of Participants with a during treatment assessment abnormality in the direction specified regardless of this abnormality at baseline. Abnormalities reported in Participants with missing baseline values are included. Baseline is the Participant's last observation prior to initiation of study drug. | Baseline; pre-dose, 1 hour (h), 4, 8, 12h post-dose Day 1, 24h post-dose Day 2, 8, 15, 29, 85 | 
| Percentage of Participants With U-wave Abnormalities | Table entries provide the percentage of Participants with a during treatment assessment abnormality in the direction specified regardless of this abnormality at baseline. Abnormalities reported in Participants with missing baseline values are included. Baseline is the Participant's last observation prior to initiation of study drug. | Baseline; pre-dose, 1 hour (h), 4, 8, 12h post-dose Day 1, 24h post-dose Day 2, 8, 15, 29, 85 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) for RO7062931 | Observed Maximum Plasma Concentration were obtained after the participants received the RO7062931 | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18h post-dose Day 1, 24, 30, 36h post-dose Day 2, Day 3, 4, 5, 6, 8 | 
| Time to Reach Maximum Plasma Concentration (Tmax) for RO7062931 | Time to reach the observed Maximum Plasma Concentration were obtained after the participants received the RO7062931. | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18h post-dose Day 1, 24, 30, 36h post-dose Day 2, Day 3, 4, 5, 6, 8 | 
| Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) for RO7062931 | Area Under the Plasma Concentration-time Curve Extrapolated to infinity was calculated based on Non-Compartment Analysis. | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18h post-dose Day 1, 24, 30, 36h post-dose Day 2, Day 3, 4, 5, 6, 8 | 
| Area Under the Plasma Concentration-Time Curve From Time Zero Until the Last Quantifiable Time-Point (AUC0-last) for RO7062931 | Area Under the Plasma Concentration-time Curve up to the last measurable concentration was calculated based on Non-Compartment Analysis | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18h post-dose Day 1, 24, 30, 36h post-dose Day 2, Day 3, 4, 5, 6, 8 | 
| Terminal Elimination Half-Life (t1/2) for RO7062931 | Terminal Half-life was calculated based on Non-Compartment Analysis. | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18h post-dose Day 1, 24, 30, 36h post-dose Day 2, Day 3, 4, 5, 6, 8 | 
| Apparent Clearance (CL/F) for RO7062931 | Apparent oral clearance was calculated from Dose/AUCinf. | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18h post-dose Day 1, 24, 30, 36h post-dose Day 2, Day 3, 4, 5, 6, 8 | 
| Apparent Volume of Distribution (Vz/F) for RO7062931 | Apparent volume of distribution was calculated from Dose/AUCinf | Pre-dose, 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18h post-dose Day 1, 24, 30, 36h post-dose Day 2, Day 3, 4, 5, 6, 8 | 
| Cumulative Amount of RO7062931 Excreted in Urine (Ae) | Ae: cumulative amount of drug excreted in urine over a 24 hour period or over defined time periods linked to the pools of urine collected. | (0-4), (4-8), (8-12), (12-24)h post-dose Day 1 | 
| Fraction of Cumulative Amount of RO7062931 Excreted in the Urine Over Total Dose (Fe) | The fraction of cumulative amount in urine were calculated based on Ae/Dose | 0-24h h post-dose Day 1 |