Effectiveness of Antiviral Treatment in Cirrhotic Patients With Low-level Hepatitis B Virus DNA Levels

• Status: Recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Multicenter, Open-label, Randomized Controlled Trial Male and female adults with liver cirrhosis due to chronic hepatitis B virus infection who have low-level viremia and are beyond treatment indications by current guidelines.

To assess the efficacy of Tenofovir Alafenamide (TAF) in reducing liver-related events (hepatocellular carcinoma, liver-related events and death, decompensated liver cirrhosis) in cirrhotic chronic hepatitis B patients with low-level viremia beyond treatment indications by current guidelines, compared with best supportive care

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Asan Medical Center
• Collaborator: National Evidence-Based Healthcare Collaborating Agency
• Treatments: Tenofovir

Criteria

Inclusion Criteria:

1. Willing and able to provide written informed consent prior to study entry

2. Age ≥40 years and ≤80 years at the time of screening

3. Chronic hepatitis B infection defined as HBsAg (+) or HBV DNA (+) for at least 6 months prior to the Screening visit, or medical records indication a chronic hepatitis B virus infection by meeting all of the following criteria at the time of screening. (1) HBsAg (+), (2) HBV DNA (+), and (3) HBcAb IgM (-)

4. Either HBeAg (+) or HBeAg (-)

5. Serum HBV DNA levels ≥20 IU/mL and <2,000 IU/mL at the time of screening

6. Evidence of liver cirrhosis defined as meeting any of the following criteria:

• Radiological evidence of liver cirrhosis by ultrasound, CT, or MRI

• Platelet count <150,000 /mm3

• Presence of esophageal or gastric varices by endoscopy in 2 years before the timing of screening

• Clinically significant portal hypertension

• Fibroscan ≥12.0 kPa (if the test was done in 6 months before the time of screening)

7. Estimated creatinine clearance ≥30 ml/min (by calculation of creatinine clearance or using the CKD-EPI equation)

8. Ability to comply with all study requirements

Exclusion Criteria:

1. Confirmed known co-infection with HCV, HIV, or HDV

2. Current alcohol (60g/day) or substance abuse judged by the investigator that will potentially interfere with subject compliance

3. Any history of, or current evidence of, clinical hepatic decompensation (e.g., ascites, encephalopathy, variceal hemorrhage, or Child-Pugh score of ≥8, with the exception of Gilbert syndrome) in 1 year before the time of screening

4. Currently on or have received therapy with Interferon or immunosuppressant (including systemic chemotherapy) within 12 months prior to the screening

5. Requirement for chronic use of systemic immunosuppressant including, but not limited to, corticosteroid (prednisone equivalent of >40 mg/day for >2 weeks), azathioprine, or monoclonal antibodies

6. Received solid organ or bone marrow transplant

7. History of severe, life-threatening or other significant sensitivity to any excipients of the study drugs

8. Any other clinical conditions (cardiovascular, respiratory, neurologic, or renal conditions) or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements.

9. Currently on or have received antiviral treatment for ≥ 2 weeks within 6 months prior to the screening

10. History or current evidence of hepatocellular carcinoma (HCC), or high α-fetoprotein (AFP) > 20 ng/mL. But, the patients with AFP > 20 ng/mL can be enrolled if AFP shows decreasing trend and there is no evidence of HCC by dynamic CT or MRI)

11. Malignancy other than hepatocellular carcinoma within the 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (within 2 years prior to screening with confirmation of no evidence of disease). Subjects under evaluation for possible malignancy are not eligible.

12. Concurrent enrollment in another clinical study for other type of antiviral treatment for CHB or immune modulatory drug within 3 months prior to randomization, participation to an observational (non-interventional) clinical studies or interventional studies not using anti-HBV or immune modulatory drugs, or during the follow-up period of an interventional study are not exclusion criteria.

13. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study