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

Chronic Hepatitis B Clinical Trial

— HBV  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02792088
• Other study ID #: ID_BVCL012
• Status: Completed
• Phase: Phase 3
• Start date: July 2015
• Est. completion date: February 2020

Study information

• Verified date: August 2022
• Source: IlDong Pharmaceutical Co Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 146
• Est. completion date: February 2020
• Est. primary completion date: February 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Korea, Republic of	Severance Hospital of Yonsei University	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
IlDong Pharmaceutical Co Ltd

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The rate of subjects who showed ALT normalized at the 48th week		at the 48th week