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

Roche

Status and phase: Completed; Phase 1

Conditions: Hepatitis B Virus

Treatments: Drug: RO7049389; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03570658

YP39406

Details and patient eligibility

About

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

Enrollment: 31 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Double Blind

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31 participants in 3 patient groups, including a placebo group

Single-Ascending Dose (SAD)

Experimental group

Description:

Participants will receive a single dose of RO7049389.

Treatment:

Drug: RO7049389

Multiple-Ascending Dose (MAD)

Experimental group

Description:

Participants will receive multiple doses of RO7049389.

Treatment:

Drug: RO7049389

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo