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

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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A Phase III, Multi-center, Randomized, Double-blinded, Parallel 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

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Besifovir 150mg
* Drug: Tenofovir 300mg


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Besifovir<br>Besifovir 150 mg q.d. | Drug: Besifovir 150mg<br>* Besifovir 150 mg q.d. + Placebo of Tenofovir Disoproxil Fumarate 300 mg q.d. + L-carnitine (L-Carn Tab. 330 mg) 660 mg q.d.<br>* Other names: Besifovir;|
| Active Comparator: Tenofovir<br>Tenofovir 300 mg q.d. | Drug: Tenofovir 300mg<br>* Placebo of Besifovir 150 mg q.d. + Tenofovir Disoproxil Fumarate 300 mg q.d. + Placebo of L-carnitine (L-Carn Tab. 330 mg) 660 mg q.d.<br>* Other names: Tenofovir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of subjects who showed HBV DNA undetected (less than 400 copies/mL (69 IU/mL)) at the 48th week |  | at the 48th week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of subjects who showed ALT normalized at the 48th week |  | at the 48th week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBV