Active clinical trials for "Hepatitis B, Chronic"

BACKGROUND: Finite nucleos(t)ide analogue (Nuc) therapy was proposed as an alternative strategy in the management of chronic hepatitis B (CHB) but there remained not data from randomized controlled trials to clarify safety and efficacy of this treatment strategy. AIMS: The investigators aimed to evaluate the safety and efficacy of finite Nuc therapy versus continuous treatment in CHB patients without liver cirrhosis and also to identify factors that may predict therapeutic responses and clinical outcomes after withdrawal of Nuc treatment for CHB MATERIAL AND METHODS: This is a multicenter randomized controlled trial conducted in Taiwan. Eligible patients are adults (age≥20 years) with CHB (chronic infection ≥ 6 months) who fulfill the APASL guideline 2016 to stop NA therapy. Those with cirrhosis, malignancy, organ transplant, autoimmune disorder, or serious underlying diseases including renal impairment were excluded. A total of 360 patients will be enrolled. Enrolled patients are randomly allocated with a 1:1 ratio to continue viral suppression with entecavir (0.5mg once daily) or tenofovir disoproxil fumarate (300mg once daily) or stop the treatment. All patients will be followed up according to the protocol recommended by a panel of APASL experts. The primary analysis for study outcomes is scheduled at 3 years after randomization and the primary outcome is seroclearance of HBsAg. There will be interim analyses scheduled at one- and two-years following randomization of the first 200 patients, and also one-and two years following randomization of the planned 360 patients, to determine whether early termination of the trial may be justified by attainment of the efficacy endpoint (10% vs 1% of HBsAg seroclearance) or concerns of the safety outcomes (significant between-group difference in mortality, acute on chronic liver failure, or acute flares with hepatic decompensation).

In the globe, about 33% (2 billion) of population has ever been infected with hepatitis B virus (HBV), and about 5% (350-400 million) were chronical HBV infection. In areas with high prevalence of hepatitis B, up to 80% of primary liver cancers are associated with HBV infection. About 25% of chronic hepatitis B virus carrier (more than 1 million people per year) eventually die of end stage liver disease associated with HBV infection, such as liver failure associated with cirrhosis and hepatocellular carcinoma. HBV replicates in the liver, which increases the risk of hepatocellular carcinoma in HBV carriers. Studies have shown that the risk of hepatocellular carcinoma (HCC) in HBV carriers was 10-100 folds higher than that of non-carriers. Clinically, there are primarily two types of antiviral drugs: α-interferons (plain and pegylated ([PEG-IFN]α-2a or α-2b) interferons) and nucleos(t)ide analogues (NUC) including lamivudine (LAM), adefovir dipivoxil (ADV), entecavir (ETV), telbivudine (LDT), tenofovir disoproxil fumarate(TDF) and tenofovir alafenamide fumarate(TAF). With the development and application of antiviral drugs in recent years, the basic goal of maintain suppression against virus replication has been achieved, and HBsAg loss is considered as function cure of antiviral therapy. However, data from clinical studies showed a very low cure rate of current antiviral drugs and a natural HBsAg loss usually is less than 3%. The vast majority of clinical patients require long-term antiviral treatment and have difficulties in treatment stop. The AI data mining system innovated by the Holy Haid owns a ten-million-scaled database and utilizes dozens of HBV-associated targets to identify 100 drugs that are most closely to the targets among the 500 commercially available drugs. With the identified 100 drugs, Holy Haid (Ying-ying Li) and Beijing Tsinghua Changgung Hospital (Lai Wei) conducted a cytological verification in mice, which indicated that the HD042 (Celecoxib) at 20uM concentration can inhibit HBV DNA, HBsAg and HBeAg by 70.87%, 88.52% and 87.55% respectively, without significant cytotoxicity. Based on this, Beijing Tsinghua Changgung Hospital (Lai Wei) retrospectively analyzed 1,114,661 patients admitted to 304 hospitals in 107 cities of 21 provinces and municipalities from January 1, 2019 to October 31, 2020 and identified 19,692 patients with the results of two HBsAg tests available and an interval of over 30 days. Among these, 3,359 patients had ever took HD042 (Celecoxib). Further analysis showed that these 3,359 patients, and screened out 383 patients who were diagnosed of hepatitis B and excluded from tumor with two HBsAg levels > 0.05IU/ml but ≤1500IU/ml. Among these, 110 patients were prescribed for more than 5 Celecoxib doses (about 30 days of treatment). Among the 110 patients, we screened out 27 patients on Celecoxib for 12 weeks whose HBsAg expression decreased by 59.2% after 12 weeks, including HBsAg clearance rate (i.e., HBsAg decreased to < 0.05IU/ mL) up to 18.5%. Celecoxib, a specific inhibitor of Cyclooxygenase 2 (COX-2), has been widely used in clinical practice as an anti-inflammatory and analgesic drug. Studies have shown that Celecoxib improves NASH by inhibiting inflammatory responses. In addition, some studies have also shown that COX-2 is highly expressed in hepatitis B related hepatocellular carcinoma, resulting in cancerous tissue microangiogenesis. Cytological test found that Celecoxib, as a COX-2 specific inhibitor, can inhibit the growth of liver cancer cells by induced apoptosis and cell cycle inhibition, and have a even stronger effect on HBsAg positive liver cancer cells. However, the inhibitory effect of Celecoxib on the hepatitis B surface antigen in patients with chronic hepatitis B remained controversial. Therefore, this study is designed to investigate the safety and efficacy of Celecoxib in the hepatitis B surface antigen loss and reduction in nucleoside-treated patients with chronic hepatitis B.

The purpose of this study is to evaluate the efficacy of the study intervention based on hepatitis B surface antigen (HBsAg) levels.

The primary objective of this study is to evaluate the antiviral efficacy of tenofovir disoproxil fumarate (tenofovir DF; TDF) versus placebo in pediatric population (aged 2 to < 12 years at the time of enrollment) with chronic hepatitis B (CHB) infection.

This is a phase2, randomized, single-blind, placebo controlled and multi-center study in adults with chronic hepatitis B virus. The study is aimed at evaluating efficacy and safety of ASC42 in combination with entecavir and pegylated interferon α-2a in subjects with chronic hepatitis B virus.

Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection. Whereas, the long-term effect of TAF to liver fibrosis is still unknown. Here, we enrolled treatment naive CHB patients with biopsy-proven significant fibrosis (METAVIR fibrosis stage ≥ F2). All enrolled subjects will be treated with TAF monotherapy for 96 weeks. After 96 weeks of therapy, the second liver biopsy will be performed to evaluate the rate of liver fibrosis regression. During this study, all subjects will be assessed for laboratory tests, imaging examination at baseline, first 12-week and every 24-week during follow-up.

The primary objectives of this study are to evaluate the safety and tolerability of study treatment(s) (selgantolimod-containing combination therapies) and to evaluate the efficacy of study treatment(s) as measured by the proportion of participants who achieve functional cure, defined as hepatitis B surface antigen (HBsAg) loss and hepatitis B virus (HBV)deoxyribonucleic acid (DNA) < lower limit of quantitation (LLOQ) at Follow-up (FU) Week 24 in participants with chronic hepatitis B (CHB).

An exploratory comparison of changes in liver fibrosis through glycemic control within and between groups after administration of Pioglitazone and Evogliptin in chronic hepatitis B patients with type 2 diabetes and liver fibrosis

The purpose of this study is to evaluate efficacy of the study intervention, based on hepatitis B surface antigen (HBsAg) levels at follow-up (FU) Week 24.

This study will assess the safety, efficacy and immune response following the sequential treatment of GlaxoSmithKline's (GSK) ASO compound (GSK3228836) and CHB-TI (GSK3528869A) in participants 18 to 65 years stable on NA treatment for CHB. The aim is to quantify the efficacy of sequential therapy as well as to determine an added value of sequential therapy over GSK3228836 therapy in CHB patients treated with NAs. In addition, the study will assess the effect of different treatment durations of GSK3228836 (12 or 24 weeks) prior to initiating GSK3528869A treatment.