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

NCT03570658 | Completed Phase 1 Results

• 1 other identifier: YP39406
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Hepatitis B Virus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• 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)

Study Arms (3)

Single-Ascending Dose (SAD)

EXPERIMENTAL

Participants will receive a single dose of RO7049389.

Drug: RO7049389

Multiple-Ascending Dose (MAD)

EXPERIMENTAL

Participants will receive multiple doses of RO7049389.

Drug: RO7049389

Placebo

PLACEBO COMPARATOR

Participants will receive either a single dose (SAD cohorts) or multiple doses (MAD cohorts) of placebo matched to RO7049389.

Drug: Placebo

Interventions

RO7049389 DRUG

RO7049389 will be administered orally either as a single dose (SAD) or as multiple doses defined by the SAD portion of the study (MAD).

Multiple-Ascending Dose (MAD); Single-Ascending Dose (SAD)

Placebo DRUG

Placebo will be administered orally at a dose and frequency matched to RO7049389.

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (1)

Huashan Hospital Affiliated to Fudan University

Shanghai, 200040, China

Location

Related Publications (1)

• 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.

  PMID: 34562067 DERIVED

MeSH Terms

Conditions

Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2018
• First Posted: June 27, 2018
• Study Start: August 24, 2018
• Primary Completion: January 28, 2019
• Study Completion: January 28, 2019
• Last Updated: February 28, 2020
• Results First Posted: February 28, 2020

Record last verified: 2020-02

Locations

CN (1)