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

NCT ID: NCT02792088

Last Updated: 2023-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 146 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2020-02-29

Brief Summary

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

• 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.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Besifovir

Besifovir 150 mg q.d.

Group Type: EXPERIMENTAL

Besifovir 150mg

Intervention Type: DRUG

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.

Tenofovir

Tenofovir 300 mg q.d.

Group Type: ACTIVE_COMPARATOR

Tenofovir 300mg

Intervention Type: DRUG

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.

Interventions

Besifovir 150mg

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.

Intervention Type: DRUG

Tenofovir 300mg

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.

Intervention Type: DRUG

Other Intervention Names

Besifovir; Tenofovir

Eligibility Criteria

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

1. Treatment with pegylated interferons within 6 months

2. Prior exposure to BSV

3. Mutations conferring resistance to ADV

4. Serum HBV DNA levels < 69 IU/mL

5. Coinfection with hepatitis C, hepatitis D or human immunodeficiency viruses

6. ALT levels ≥ 10 x ULN

7. 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)

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)

9. Decreased estimated glomerular filtration rates < 50 mL/min

10. Presence of hepatocellular carcinoma or elevated alpha feto-protein > 50 ng/mL

11. Current use of aspirin or nonsteroidal anti-inflammatory drugs within 2 month

12. Current use of immunosuppressive agents within 6 months

13. Current use of high dose corticosteroids (prednisolone > 20 mg/day or equivalent dose over 14 days) with 3 months

14. History of malignancy within 5 years

15. Subjects who are participating in other clinical trials

16. Pregnant or lactating women

17. Hypersensitivity to the study drugs

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IlDong Pharmaceutical Co Ltd

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kwang-Hyub Han, M.D, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Severance Hospital of Yonsei University

Locations

Severance Hospital of Yonsei University

Seoul, , South Korea

Countries

South Korea

Other Identifiers

ID_BVCL012

Identifier Type: -

Identifier Source: org_study_id