An Efficacy, Safety, and Pharmacokinetics Study of JNJ-56136379 in Participants With Chronic Hepatitis B Virus Infection
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Virus Diseases; Herpesviridae Infections; Hepatitis
Intervention: JNJ-56136379; Placebo; NA (ETV or TDF)
Intervention description: Participants will receive JNJ-56136379 tablet orally.; Participants will receive matching placebo tablet orally.; Participants will receive NA (ETV or TDF) tablet orally as per approved label.
Intervention MeSH terms: JNJ-56136379
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 232.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The main purpose of this study is to evaluate efficacy of 24 weeks of study treatment, in
      terms of changes in hepatitis B surface antigen (HBsAg) levels.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants must have a body mass index (weight in kilogram (kg) divided by the
             square of height in meters) of 18.0 to 35.0 kilogram / square meter (kg/m^2), extremes
             included

          -  Participants must have chronic hepatitis B virus infection (CHB) infection documented
             by: Serum hepatitis B surface antigen (HBsAg)-positive at screening and serum HBsAg-
             or hepatitis B virus (HBV) deoxyribonucleic acid (DNA)-positive at least 6 months
             prior to screening; Serum immunoglobulin M (IgM) anti- hepatitis B core-related (HBc)
             antibody negative at screening

          -  In participants currently not being treated (Treatment Arms 1-2-3 and 6-7-8):
             Participants must not be receiving any CHB treatment at screening, that is, Have never
             received treatment with HBV antiviral medicines, including NAs or interferon (IFN)
             products, OR Have not been on treatment with HBV antiviral medicines, including
             nucleos(t)ide analog (NA)s or IFN products within 6 months prior to baseline (first
             intake of study drugs), and participants must be HBeAg-positive and have HBV DNA
             greater than or equal to (>=) 20,000 International Units Per Milliliter (IU/mL), OR be
             hepatitis B e antigen (HBeAg)-negative and have HBV DNA >=2,000 IU /mL at screening,
             and participants must have HBsAg greater than (>) 250 IU/mL at screening, and
             participants must have alanine aminotransferase (ALT) > upper limit of normal (ULN)
             and less than or equal to (<=) 5 * ULN at screening, determined in the central
             laboratory

          -  In virologically suppressed participants (Treatment Arms 4-5 and 9-10): Participants
             must be virologically suppressed by current NA treatment (entecavir (ETV) or tenofovir
             disoproxil fumarate (TDF)) as defined by HBV DNA less than (<) 60 IU/mL at screening
             and at least 6 months prior to screening, and participants must be on the same NA
             treatment (ETV or TDF) and the same dose for >=12 months prior to screening, and
             participants must have HBsAg > 250 IU/mL at screening, and participants must have ALT
             <=2*ULN at screening

          -  Participants must have: A liver biopsy result classified as Metavir F0-F2 within 1
             year prior to screening or at the time of screening, OR FibroScan liver stiffness
             measurement <8.0 kilopascal (kPa) within 6 months prior to screening or at the time of
             screening

        Exclusion Criteria:

        Main Study:

          -  Participants who test positive for anti-hepatitis B surface (HBs) antibodies

          -  Participants with current hepatitis A virus infection (confirmed by hepatitis A
             antibody immunoglobulin M [IgM]), hepatitis D virus (HDV) infection (confirmed by HDV
             antibody), hepatitis E virus infection (confirmed by hepatitis E antibody IgM), or
             human immunodeficiency virus (HIV)-1 or HIV-2 infection (confirmed by antibodies) at
             screening; participants with a history of or current HCV infection (confirmed by HCV
             antibody). Evidence of other active infection (bacterial, viral, fungal, including
             acute tuberculosis) deemed clinically relevant by the investigator that would
             interfere with study conduct or its interpretation will also lead to exclusion

          -  Participants with any evidence of hepatic decompensation at any time point prior to or
             at the time of screening: Direct bilirubin >1.2* ULN, or International normalized
             ratio (INR) >1.5* ULN, or Serum albumin < lower limit of normal (LLN), or documented
             history or current evidence of variceal bleeding, ascites, or hepatic encephalopathy

          -  Participants with a history of cardiac arrhythmia (example, extrasystoli, tachycardia
             at rest), history of risk factors for Torsades de Pointes syndrome (example,
             hypokalemia, family history of long QT syndrome) or history or other clinical evidence
             of significant or unstable cardiac disease (example, angina, congestive heart failure,
             myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart
             disease, and/or clinically significant 12 lead electrocardiograms (ECGs)
             abnormalities), moderate to severe valvular disease, or uncontrolled hypertension at
             screening

          -  Participants with contraindications to the use of ETV or TDF per local prescribing
             information

        Substudy:

          -  Presence of coagulopathy or hemoglobinopathy (including sickle cell disease,
             thalassemia)

          -  Use of any anti-coagulant, anti-platelet, or non-steroidal anti-inflammatory drug
             medications from 10 days before until 5 days after each liver biopsy

          -  Presence of ascites, focal liver lesions, and other findings that would be
             contraindications for liver biopsies