A Study of RO7239958 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers and Participants With Chronic Hepatitis B Virus Infection

Phase 1TerminatedNCT03762681

Hoffmann-La Roche55 enrolled

Overview

This study is designed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending doses in healthy volunteers (HV) and participants diagnosed with chronic hepatitis B (CHB).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Hepatitis B Virus Infection

Interventions

RO7239958DRUG

Solution for injection, subcutaneous use (SC).

PlaceboOTHER

Sodium chloride solution for injection, SC

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: All Parts -Female participants should be of non-childbearing potential and male participants who are with pregnant partners or partners of childbearing potential must agree to remain abstinent or use contraceptive measures Part 1 (SAD HV only) * Healthy, as judged by the Investigator * Non-smoker (nor tobacco containing products) for at least 90 days prior to dosing on Day 1, and agrees to remain non-smoker during the study Part 2 (CHB only) * Positive serum HBsAg status for \> 6 months prior to screening * Serum HBsAg level ≥ 250 IU/mL at screening * On stable entecavir or tenofovir (alone or in combination) treatment and having received the same drug in the 3 months prior to randomisation * HBV DNA below the lower limit of quantification (LLQ) for ≥ 6 months prior to screening by local testing, and confirmed at screening * Screening laboratory values (including hematology, chemistry, urinalysis) within normal ranges * No past or current diagnosis of cirrhosis Exclusion Criteria: All Parts * History or presence of significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological disorders, or diagnosed central or peripheral neurological disease, capable of altering the absorption, metabolism, or elimination of drugs, or constituting a risk when taking the study treatment, or of interfering with the interpretation of the data * History of lymphoma, leukemia, or malignancy within the past five years * Positive for human immunodeficiency virus (HIV) infection * Participant under judicial supervision, guardianship or curatorship Part 1 (SAD HV only) * Screening ECG showing clinically relevant abnormalities * Abnormal blood pressure * History or presence of liver disease, or known hepatic or biliary abnormalities * Alanine aminotransferase (ALT) ≥1.5 × upper limit of normal (ULN) * Any clinically significant out of range findings in other laboratory test results or any other clinically significant (as judged by the Investigator) abnormalities in the physical examination at screening and on Day -1 * Positive for hepatitis B surface antigen (HBsAg), or hepatitis B core total antibody \[anti-HBc\]), or hepatitis C virus (HCV) antibody test result Part 2 (CHB only) * History or presence of bridging fibrosis or cirrhosis or decompensated liver disease * History or presence of a medical condition associated with liver disease other than HBV infection. Other known hepatic or biliary abnormalities * History of or suspicion of hepatocellular carcinoma or alpha fetoprotein (AFP) ≥13 ng/mL * History of having received (in the last six months) or currently receiving any systemic antineoplastic (including radiation) or immune-modulatory treatment (including systemic corticosteroids) * History of organ transplantation * Estimated glomerular filtration rate (eGFR) \<70 mL/min/1.73m\^2 * Confirmed QT interval corrected using Fridericia's formula (QTcF) \>450 ms * Expected to need any other systemic antiviral therapy at any time during participation in the study * Positive hepatitis C antibody test

Locations (14)

Acibadem City Clinic Tokuda Hospital Ead

Sofia, Bulgaria

COMAC Medical; Clinical Research Unit for Phase I

Sofia, Bulgaria

Queen Mary Hospital

Hong Kong, Hong Kong

Outcomes

Primary Outcomes

Number of Participants With Adverse Events (AEs)

An adverse event (AE) was defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product (including investigational drug) during the course of a clinical investigation. An AE could therefore be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease that was temporally associated with the use of the investigational product, regardless of whether it was considered to be related to the investigational product or not.