Status:

COMPLETED

A Study of Switching From Entecavir to Tenofovir Disoproxil Fumarate in Subjects With Chronic Hepatitis B

Lead Sponsor:

GlaxoSmithKline

Conditions:

Hepatitis B, Chronic

Eligibility:

All Genders

20-69 years

Phase:

PHASE4

Brief 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 chroni...

Eligibility Criteria

Inclusion

  • 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

  • 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.

Key Trial Info

Start Date :

October 2 2017

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

November 25 2019

Estimated Enrollment :

75 Patients enrolled

Trial Details

Trial ID

NCT03258710

Start Date

October 2 2017

End Date

November 25 2019

Last Update

August 4 2020

Active Locations (18)

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Page 1 of 5 (18 locations)

1

GSK Investigational Site

Aichi, Japan, 467-8602

2

GSK Investigational Site

Chiba, Japan, 270-1694

3

GSK Investigational Site

Ehime, Japan, 790-0024

4

GSK Investigational Site

Ehime, Japan, 790-8524