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

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

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

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: RO7062931; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Shatin, New Territories, Hong Kong
    • Prince of Wales Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: SEQUENTIAL
• Masking: DOUBLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: RO7062931 0.3mg/kg; Participants will receive subcutaneously (SC) 0.3 milligram per kilogram (mg/kg) of RO7062931.	Drug: RO7062931; 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.; Drug: Placebo; Matching placebo will be administered subcutaneously (SC).
EXPERIMENTAL: RO7062931 1.0mg/kg; Participants will receive subcutaneously (SC) 1.0 milligram per kilogram (mg/kg) of RO7062931.	Drug: RO7062931; 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.; Drug: Placebo; Matching placebo will be administered subcutaneously (SC).
EXPERIMENTAL: RO7062931 2.0mg/kg; Participants will receive subcutaneously (SC) 2.0 milligram per kilogram (mg/kg) of RO7062931.	Drug: RO7062931; 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.; Drug: Placebo; Matching placebo will be administered subcutaneously (SC).
EXPERIMENTAL: RO7062931 4.0mg/kg; Participants will receive subcutaneously (SC) 4.0 milligram per kilogram (mg/kg) of RO7062931.	Drug: RO7062931; 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.; Drug: Placebo; Matching placebo will be administered subcutaneously (SC).
PLACEBO_COMPARATOR: Placebo; Participants will receive matching placebo.	Drug: Placebo; Matching placebo will be administered subcutaneously (SC).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 3, 2018
• Primary Completion (ACTUAL): July 5, 2019
• Study Completion (ACTUAL): July 5, 2019

Study Registration Dates

• First Submitted: April 13, 2018
• First Submitted That Met QC Criteria: April 13, 2018
• First Posted (ACTUAL): April 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 3, 2020
• Last Update Submitted That Met QC Criteria: July 14, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: YP39432

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No