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

Healthy Participants Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03505190
• Other study ID #: YP39432
• Status: Completed
• Phase: Phase 1
• Start date: May 3, 2018
• Est. completion date: July 5, 2019

Study information

• Verified date: July 2020
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: July 5, 2019
• Est. primary completion date: July 5, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Participants

Intervention

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.
• Placebo
Matching placebo will be administered subcutaneously (SC).

Locations

Country	Name	City	State
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Prince of Wales Hospital	Shatin, New Territories

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Hong Kong, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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