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

• Status: Completed
• Trial end date: 2019-11-25
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Treatments: Entecavir; Tenofovir

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.