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

Phase 3

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Drug: Tenofovir 300mg; Drug: Besifovir 150mg

• Registration Number: NCT02792088
• Lead Sponsor: IlDong Pharmaceutical Co Ltd

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.

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2016-05-31
• Study First Submitted QC: 2016-06-06
• Study First Posted: 2016-06-07
• Primary Completion: 2020-02
• Study Completion: 2020-02
• Status Verified: 2022-08
• Last Update Submitted: 2023-02-20
• Last Update Posted: 2023-02-21

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 146

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tenofovir	Tenofovir 300mg	Tenofovir 300 mg q.d.
Besifovir	Besifovir 150mg	Besifovir 150 mg q.d.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
The rate of subjects who showed ALT normalized at the 48th week	at the 48th week

Trial Locations

Locations (1)

Severance Hospital of Yonsei University; 🇰🇷 Seoul, Korea, Republic of