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

• Status: Terminated
• Trial end date: 2020-04-06
• Target enrollment: 0
• Participant gender: All

Summary

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).

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Hoffmann-La Roche

Criteria

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