Study to Assess the Antiviral Activity and Safety Endpoints for the Treatment of Besifovir 150mg Compared to Tenofovir 300mg in Chronic Hepatitis B Patients Who Have Resistance to Nucleoside Analogues (HBV)

IlDong Pharmaceutical

Status and phase

Completed

Phase 3

Conditions

Chronic Hepatitis B

Treatments

Drug: Besifovir 150mg

Drug: Tenofovir 300mg

Study type

Interventional

Funder types

Industry

Identifiers

NCT02792088

ID_BVCL012

Details and patient eligibility

About

To prove that a study drug is noninferior to a control drug with a proportion of subjects who showed HBV DNA undetected (less than 400 copies/mL (69 IU/mL)) at the 48th week after 48-week administration of Besifovir 150 mg, or Tenofovir 300 mg as a control drug to chronic hepatitis B patients

Full description

Screening Period Subject registration is conducted with confirming selection and exclusion criteria after a written consent form is obtained within 42 days before clinical trial drug administration.
Baseline Subjects who visit on the date of starting clinical trial drug administration are randomized to a test group or a control group at a ratio of 1:1. Double blindness is applied for both groups.
Treatment period Subjects are orally administered with a clinical trial drug q.ds.i.d. for 48 weeks and visit at the 0, 4th, 12th, 24th, 36th, and 48th week for an HBV DNA test, laboratory tests, a physical test, vital signs, and adverse events.
Follow-up period Subjects are provided with appropriate treatment after completing the 48-week trial or dropping out. Subjects visit once at the 60th week for follow-up of adverse events, such as acute deterioration of hepatitis B, and HBV DNA test results. If any treatment is not conducted after 48-week administration, subjects visit at intervals of four weeks until a follow-up visit (60th week) and the same tests with the 24th week visit (Visit 5) are conducted. However, subjects who participate in a 48-week separate extended trial conducted after 48-week administration in this clinical trial do not have a follow-up period.

Enrollment

146 patients

Sex

All

Ages

20+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients who show positive HBsAg or has a history of chronic hepatitis B for the last six months or more before screening
Patients who showed positive HBsAg during screening
Have developed nucleoside analogue resistant HB
Had no received nucleotide analogue

Exclusion criteria

Treatment with pegylated interferons within 6 months
Prior exposure to BSV
Mutations conferring resistance to ADV
Serum HBV DNA levels < 69 IU/mL
Coinfection with hepatitis C, hepatitis D or human immunodeficiency viruses
ALT levels ≥ 10 x ULN
Evidence of decompensated liver disease (Total bilirubin > 2 x ULN, prothrombin time > 6 sec prolonged or INR >1.5, serum albumin <2.8 g/dL, uncontrolled ascites, overt hepatic encephalopathy, or Child-Pugh score ≥8)
Certain laboratory abnormalities (Hemoglobin < 9.0 g/dL, absolute neutrophil count (ANC) < 1 x 109/L (1000/mm3), platelet count < 75 x 109/L (75 x 103/mm3), serum Creatinine > 1.5 mg/dL, or serum amylase > 2 x ULN and Lipase > 2 x ULN)
Decreased estimated glomerular filtration rates < 50 mL/min
Presence of hepatocellular carcinoma or elevated alpha feto-protein > 50 ng/mL
Current use of aspirin or nonsteroidal anti-inflammatory drugs within 2 month
Current use of immunosuppressive agents within 6 months
Current use of high dose corticosteroids (prednisolone > 20 mg/day or equivalent dose over 14 days) with 3 months
History of malignancy within 5 years
Subjects who are participating in other clinical trials
Pregnant or lactating women
Hypersensitivity to the study drugs