A Study of Switching From Entecavir to Tenofovir Disoproxil Fumarate in Subjects With Chronic Hepatitis B
Condition: Hepatitis B, Chronic
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Tenofovir Disoproxil Fumarate
Intervention description: Tenofovir Disoproxil Fumarate is a nucleos(t)ide analogue that inhibits HBV growth. All subjects will receive one tablet of TDF 300 mg once daily orally for 96 weeks.
Intervention MeSH terms: Tenofovir
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Intervention model description: This is a single arm study where on-going ETV treatment is switched to TDF treatment. There is no randomization in this study.
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Minimum age: 20 Years
Maximum age: 69 Years
Healthy volunteers: No
Keywords: Tenofovir Disoproxil Fumarate; safety; chronic hepatitis B; virological effect

Summary:

      Tenofovir Disoproxil Fumarate is a nucleos(t)ide analogue that inhibits Hepatitis B Virus
      (HBV) growth, and is marketed in Japan with an indication for inhibition of HBV growth in
      subjects with chronic hepatitis B associated with HBV growth and abnormal liver function.
      This study has been planned to evaluate the virological effects and safety of switching from
      ETV to TDF in chronic hepatitis B (hepatitis B e-antigen [HBeAg])-positive and HBV-
      deoxyribonucleic acid (DNA) undetectable subjects. This study is designed as a multi-center,
      one-arm, post-marketing clinical study to investigate the HBsAg reduction in subjects who
      have not achieved the long-term goal, the loss of hepatitis B surface antigen (HBsAg). The
      study will be conducted in HBeAg-positive and HBV-DNA undetectable subjects treated with ETV.
      After switching ETV to TDF, TDF will be administered for 96 weeks. Approximately 80 subjects
      will be screened to achieve 65 evaluable subjects.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must be 20 to 69 years of age inclusive, at the time of signing the informed
             consent

          -  Male and female subjects. A female subject is eligible to participate if she is not
             pregnant and not breastfeeding, and at least one of the following conditions applies:

               -  Not a woman of childbearing potential (WOCBP), OR

               -  A WOCBP who agrees to follow the contraceptive guidance during the treatment
                  period and for at least 4 days after the last dose of study treatment

          -  Capable of giving signed informed consent form (ICF)

          -  Subjects with chronic hepatitis B (CHB) (excluding hospitalized subjects)

          -  Subjects treated with ETV for at least 2 years prior to initiation of study treatment.

          -  The serum HBV-DNA level at screening is below the limit of quantitation (< 2.1 Log10
             copies/milliliter [mL] or < 20 international unit [IU]/mL).

          -  Subjects with serum HBeAg positive at screening

          -  Meet either of the following serum HBsAg levels at screening:

               -  Serum HBsAg 80 < to < 800 IU/mL and fluctuation range is equal or more than -0.1
                  Log10 IU/mL per year

               -  Serum HBsAg >=800 IU/mL

          -  Meet all of the following criteria at screening:

               -  Creatinine clearance (CLcr) >=70 mL/minute. CLcr is calculated using the
                  following Cockcroft-Gault formula.

        Male: CLcr = (body weight in kilogram [kg] multiplied by [140 minus age in years]) divided
        by (72 multiplied by serum creatinine [milligram {mg}/deciliter {dL}]) Female: CLcr = CLcr
        (male) multiplied by 0.85

          -  Hemoglobin >= 8 gram/dL

          -  WBC >=1000 per cubic millimeter (mm^3)

        Exclusion Criteria:

          -  QTc > 450 millisecond (msec) or > 480 msec for subjects with bundle branch block

          -  Received any interferon or Hepatitis B vaccine therapy within 24 weeks prior to
             initiation of the study treatment.

          -  Received overdose of nonsteroidal anti-inflammatory drugs (NSAIDs) (excluding
             temporary or topical use) within 7 days prior to initiation of the study treatment.

          -  Received any of the following drugs within 8 weeks prior to initiation of the study
             treatment (excluding topical products such as ointment and/or cream etc).

               -  Drugs causing renal impairment (examples: aminoglycosides, amphotericin B,
                  vancomycin, foscarnet, cisplatin, pentamidine, tacrolimus, cyclosporine, some
                  contrast mediums [ionic high-osmolar contrast media, ionic low-osmolar contrast
                  media]

               -  Competitors of renal excretion (except temporary use, example: probenecid)

               -  Immunosuppressants (examples: azathioprine, cycolphosphamide) or
                  chemotherapeutics (example: etoposide)

               -  Glucocorticoid preparation

          -  Received TDF, Adefovir pivoxil (ADV) or Tenofovir Alafenamide Fumarate (TAF) within 2
             years prior to initiation of the study treatment

          -  Participation in another clinical study within 6 months prior to screening, or planned
             participation in another clinical study simultaneously with this study.

          -  Co-infection with human immunodeficiency virus (HIV) or hepatitis C virus (HCV)

          -  Subjects with serious complication other than compensated CHB (cancer, significant
             renal, cardiovascular, pulmonary, or neurological disease, uncontrollable diabetes,
             etc.)

          -  Received or have a plan for solid organ or bone marrow transplantation

          -  Has proximal tubulopathy.

          -  Subjects with decompensated CHB who meet the following: direct bilirubin > 1.5 times
             upper limit of normal (ULN), Prothrombin Time (PT) < 60%, platelets < 75,000/mm3 and
             serum albumin < 3.0 g/dL

          -  Autoimmune hepatitis (Antinuclear titer > 1:160), excluding CHB

          -  Subjects with or suspected of having hepatocellular carcinoma (HCC) (including both
             primary and metastatic) from diagnostic imaging at screening, or with serum
             alpha-fetoprotein (AFP) > 50 nanogram (ng)/mL at screening

          -  History of HCC (except subjects who underwent resection or received curative treatment
             by radiofrequency, and with AFP <=10 ng/mL at screening)

          -  Woman who is pregnant, possibly pregnant, lactating or planning a pregnancy during the
             study period.

          -  Psychiatry disorder or cognitive disorder that may affect the subject's ability to
             give informed consent or to follow specified study procedures.

          -  Subjects with a history of alcohol or drug abuse

          -  Subjects whom the investigator (or sub-investigator) considers ineligible for the
             study.

          -  Subjects with hypersensitivity to study treatments or their components, nucleoside
             and/or nucleotide analogues. Subjects with drug allergy that, in the investigator's
             (sub-investigator's) [or medical monitor's] opinion, labeled contraindication for
             participation in the study, or other allergy.