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

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

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

Study Overview

• Status: Completed
• Conditions: Hepatitis B Virus
• Intervention / Treatment: Drug: RO7049389; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai City, China, 200040
    • Huashan Hospital Affiliated to Fudan University

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 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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	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)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Wu X, Feng S, Zhang J, Zhang W, Zhang Y, Zhu M, Triyatni M, Zhao N, Bo Q, Jin Y. Evaluation of the safety, tolerability, and pharmacokinetics of RO7049389 in healthy Chinese volunteers. Clin Transl Sci. 2022 Jan;15(1):195-203. doi: 10.1111/cts.13134. Epub 2021 Sep 25.

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2018
• Primary Completion (Actual): January 28, 2019
• Study Completion (Actual): January 28, 2019

Study Registration Dates

• First Submitted: June 18, 2018
• First Submitted That Met QC Criteria: June 18, 2018
• First Posted (Actual): June 27, 2018

Study Record Updates

• Last Update Posted (Actual): February 28, 2020
• Last Update Submitted That Met QC Criteria: February 17, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Hepatitis B
• Other Study ID Numbers: YP39406

Drug and device information, study documents

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