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

Phase 1

Completed

• Conditions: Healthy Participants
• Interventions: Drug: RO7062931; Drug: Placebo

• Registration Number: NCT03505190
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-04-13
• Study First Submitted QC: 2018-04-13
• Study First Posted: 2018-04-23
• Study Start: 2018-05-03
• Primary Completion: 2019-07-05
• Study Completion: 2019-07-05
• Results First Submitted: 2020-06-10
• Status Verified: 2020-07
• Results First Submitted QC: 2020-07-14
• Last Update Submitted: 2020-07-14
• Results First Posted: 2020-08-03
• Last Update Posted: 2020-08-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
RO7062931 0.3mg/kg	Placebo	Participants will receive subcutaneously (SC) 0.3 milligram per kilogram (mg/kg) of RO7062931.
RO7062931 1.0mg/kg	RO7062931	Participants will receive subcutaneously (SC) 1.0 milligram per kilogram (mg/kg) of RO7062931.
RO7062931 0.3mg/kg	RO7062931	Participants will receive subcutaneously (SC) 0.3 milligram per kilogram (mg/kg) of RO7062931.
RO7062931 1.0mg/kg	Placebo	Participants will receive subcutaneously (SC) 1.0 milligram per kilogram (mg/kg) of RO7062931.
RO7062931 2.0mg/kg	RO7062931	Participants will receive subcutaneously (SC) 2.0 milligram per kilogram (mg/kg) of RO7062931.
RO7062931 2.0mg/kg	Placebo	Participants will receive subcutaneously (SC) 2.0 milligram per kilogram (mg/kg) of RO7062931.
RO7062931 4.0mg/kg	RO7062931	Participants will receive subcutaneously (SC) 4.0 milligram per kilogram (mg/kg) of RO7062931.
RO7062931 4.0mg/kg	Placebo	Participants will receive subcutaneously (SC) 4.0 milligram per kilogram (mg/kg) of RO7062931.
Placebo	Placebo	Participants will receive matching placebo.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Adverse Events and AEs of Special Interest	Up to 16 weeks	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
Percentage of Participants With Marked Laboratory Abnormalities Based on Hematology, Blood Chemistry, Coagulation and Urinalysis Test Results	Baseline, Day 2, 8, 15, 29, 85	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.
Percentage of Participants With Electrocardiogram (ECG) Abnormalities	Baseline; pre-dose, 1 hour (h), 4, 8, 12h post-dose Day 1, 24h post-dose Day 2, 8, 15, 29, 85	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.
Percentage of Participants With T-wave Abnormalities	Baseline; pre-dose, 1 hour (h), 4, 8, 12h post-dose Day 1, 24h post-dose Day 2, 8, 15, 29, 85	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.
Percentage of Participants With U-wave Abnormalities	Baseline; pre-dose, 1 hour (h), 4, 8, 12h post-dose Day 1, 24h post-dose Day 2, 8, 15, 29, 85	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.

Secondary Outcome Measures

Name	Time	Method
Cumulative Amount of RO7062931 Excreted in Urine (Ae)	(0-4), (4-8), (8-12), (12-24)h post-dose Day 1	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.
Maximum Plasma Concentration (Cmax) for 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	Observed Maximum Plasma Concentration were obtained after the participants received the RO7062931
Time to Reach Maximum Plasma Concentration (Tmax) for 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 the observed Maximum Plasma Concentration were obtained after the participants received the RO7062931.
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) for 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 Extrapolated to infinity was calculated based on Non-Compartment Analysis.
Area Under the Plasma Concentration-Time Curve From Time Zero Until the Last Quantifiable Time-Point (AUC0-last) for 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 up to the last measurable concentration was calculated based on Non-Compartment Analysis
Apparent Volume of Distribution (Vz/F) for 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	Apparent volume of distribution was calculated from Dose/AUCinf
Fraction of Cumulative Amount of RO7062931 Excreted in the Urine Over Total Dose (Fe)	0-24h h post-dose Day 1	The fraction of cumulative amount in urine were calculated based on Ae/Dose
Terminal Elimination Half-Life (t1/2) for 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	Terminal Half-life was calculated based on Non-Compartment Analysis.
Apparent Clearance (CL/F) for 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	Apparent oral clearance was calculated from Dose/AUCinf.

Trial Locations

Locations (2)

Queen Mary Hospital; 🇭🇰 Hong Kong, Hong Kong

Prince of Wales Hospital; 🇭🇰 Shatin, New Territories, Hong Kong