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

NCT04780204 | Active Not Recruiting Phase 4 FDA Drug

• 1 other identifier: IN-KR-320-6132
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 10

Brief Summary

Multicenter, Open-label, Single arm Trial with Matched Historical controls. Male and female adults with compensated liver cirrhosis due to chronic hepatitis B virus infection who have low-level viremia. 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 compared with matched historical controls.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Cumulative incidence rate of composite clinical events

  hepatocellular carcinoma, death, liver transplantation, decompensated liver cirrhosis defined as Child-Pugh score ≥8, liver cirrhosis-related complications,liver-related unexpected hospital admission

  From randomization the composite clinical events will be collected every 6weeks , assessed up to 36months

Secondary Outcomes (1)

• Cumulative incidence

  From randomization the composite clinical events will be collected every 1year , assessed up to 3years

Study Arms (2)

Antiviral Treatment

EXPERIMENTAL

Tenofovir Alafenamide 25mg once daily , Oral

Drug: Treatment

Matched Historical Controls

NO INTERVENTION

Patients who did not receive antiviral treatment during their follow-up period, and matched with the treatment group in a 1:2 ratio according to their baseline characteristics

Interventions

Treatment DRUG

Tenofovir Alafenamide 25 mg oral once daily

Also known as: Tenofovir alafenamide

Antiviral Treatment

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent prior to study entry
• Age ≥30 years and ≤80 years at the time of screening
• 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 (-)
• Either HBeAg (+) or HBeAg (-)
• Serum HBV DNA levels ≥20 IU/mL and \<2,000 IU/mL at the time of screening
• 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)
• Estimated creatinine clearance ≥30 ml/min (by calculation of creatinine clearance or using the CKD-EPI equation)
• Ability to comply with all study requirements

You may not qualify if:

• Confirmed known co-infection with HCV, HIV, or HDV
• Current alcohol (60g/day) or substance abuse judged by the investigator that will potentially interfere with subject compliance
• 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
• Currently on or have received therapy with Interferon or immunosuppressant (including systemic chemotherapy) within 12 months prior to the screening
• 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
• Received solid organ or bone marrow transplant
• History of severe, life-threatening or other significant sensitivity to any excipients of the study drugs
• 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.
• Currently on or have received antiviral treatment for ≥ 2 weeks within 6 months prior to the screening
• 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)
• 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.
• Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study

Sponsors & Collaborators

• Asan Medical Center: lead
• National Evidence-Based Healthcare Collaborating Agency: collaborator

Study Sites (10)

Kyungpook National University Hospital

Daegu, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Chung-Ang University Hospital

Seoul, South Korea

Location

Konkuk University Hospital

Seoul, South Korea

Location

Korea University Guro Hospital

Seoul, South Korea

Location

Kyung-Hee University Hospital

Seoul, South Korea

Location

Samsung Medical center

Seoul, South Korea

Location

Seoul National University Bundang Hospital

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Ulsan University Hospital

Ulsan, South Korea

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

Therapeutics; tenofovir alafenamide

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Young-Suk Lim, PhD

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: March 1, 2021
• First Posted: March 3, 2021
• Study Start: August 23, 2021
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: October 9, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (10)