A Study of RO7239958 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers and Participants With Chronic Hepatitis B Virus Infection
Condition: Hepatitis B Virus Infection
MeSH terms: Infections; Communicable Diseases; Hepatitis A; Virus Diseases; Hepatitis B; Hepatitis B, Chronic; Herpesviridae Infections; Hepatitis
Intervention: RO7239958; Placebo
Intervention description: Solution for injection, subcutaneous use (SC).; Sodium chloride solution for injection, SC
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 55.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers

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).
    

Eligibility 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