Clinical Research Directory

Adaptability of an Undetectable = Untransmissible Model for HBV

Persons with chronic hepatitis B (HBV) infection and active viremia are infectious and may transmit virus to others through blood/body fluid exposure. Immune tolerant treatment naive persons with hepatitis B infection express anxiety regarding disclosure of their infection status and significant fear of transmission to their partners leading to social isolation and impact on their personal lives. This study will provide data correlating serum and body fluid viral levels in persons with chronic hepatitis B infection not on therapy and those with viral suppression on long-term anti-retroviral therapy (ART) that may support the concept of "Undetectable=Untransmissible" (U=U) in patients with chronic hepatitis B.

Chronic Hepatitis b Patients Switch to tAf After Discontinuation of Nucleoside Analogue

We will conduct a phase 4, multicenter, open-label trial at 8 academic centers in Taiwan. Chronic hepatitis B patients receiving oral antiviral therapy (entecavir \[ETV\], tenofovir disoproxil fumarate \[TDF\]) for at least 1 year, and fulfil the following nucleos(t)ide analogs discontinuation criteria. After nucleos(t)ide analogs discontinuation, patients had a clinical relapse and retreatment regimen switches to TAF. The protocol will be approved by Institutional Review Board (IRB) or Research ethic committee (REC) of each site and will be conducted in accordance with the principles of Declaration of Helsinki and the International Conference on Harmonization for Good Clinical Practice. Each patient provides written informed consent before enrollment.

Stopping Antiviral Treatment in Chronic Hepatitis B

Chronic hepatitis B (CHB) infection affected 292 million individuals in the world, translating to about 3.9% of global prevalence. Up to 40% of patients with CHB will develop liver-related complications. Many patients require long-term oral antiviral therapy since off-treatment sustained virological control can only be achieved in a minority of patients. It is uncommon for patients taking long-term antivirals to be able to stop the treatment if favorable factors are not present. Those include low viral load, long enough duration of treatment, and absence of cirrhosis. Some studies have found that inducing a mild flare is beneficial for achieving functional cure in chronic hepatitis B infection. There is lack of data in the immunological and virological profile in patients who stop their long-term antiviral therapy, and in those who developed flare after treatment cessation.

Effects of Empagliflozin on Fibrosis and Cirrhosis in Chronic Hepatitis B Patients

Chronic hepatitis B (CHB) affects 257million individuals worldwide. In 2017, it caused around 39.7 million cases of cirrhosis and 0.4 million cirrhosis-related deaths in 2017. However, there is no specific treatment for liver fibrosis/cirrhosis. Although nucleos(t)ide analogues (NAs) profoundly suppress viral replication, fibrosis/cirrhosis progression can still occur in NA-treated patients. Sodium-glucose cotransporter type-2 (SGLT2) inhibitors are antidiabetic drugs that may prevent fibrosis/cirrhosis progression by reducing hepatic steatosis/inflammation, dampening renin-angiotensin aldosterone system (RAAS) activation, and reducing fluid retention, effects of which are independent of glycemic control. Clinical studies in diabetic patients show SGLT2 inhibitors reduce hepatis steatosis/inflammation, regress ascites (a cirrhotic complication), and improve liver function parameters and survival prognosis in terms of model for end-stage liver disease (MELD) score. There are currently no randomized controlled trials (RCTs) on role of SGLT2 inhibitors in preventing fibrosis/cirrhosis progression in CHB patients. Magnetic resonance elastography (MRE) and transient elastography (TE) are non-invasive techniques for liver stiffness measurement (LSM), although MRE is more accurate than TE. The investigators propose a double-blind, randomized, placebo-controlled trial to compare effect of empagliflozin (an SGLT2 inhibitor) with placebo (1:1 ratio) in preventing fibrosis progression in both diabetic and non-diabetic NA-treated CHB patients with significant/advanced fibrosis or compensated cirrhosis. 108 patients will be randomly sampled from our pre-existing TE database. Empagliflozin 10mg daily will be given to treatment arm. Placebo pills will be manufactured identical in appearance to empagliflozin. Subjects will receive active or placebo pills for three years, and undergo clinical, anthropometric and laboratory assessments (at baseline, weeks 8, 16, and every 4 months thereafter). They will undergo LSM by TE at baseline, end of first, second and third year, and by MRE at baseline and end of third year. Primary outcome is difference in change to liver stiffness (measured by MRE) from baseline between the two groups at the end of third year. The study results will determine whether SGLT2 inhibitors can prevent hepatic fibrosis/cirrhosis progression in NA-treated CHB patients.

To Evaluate the Efficacy, Safety and Population Pharmacokinetics of GST-HG141 in Patients With Chronic Hepatitis B (CHB) Who Have an Inadequate Response to Antiviral Drug Treatment

This study is a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial, aiming to evaluate the efficacy and safety of GST-HG141 in patients with chronic hepatitis B who have an inadequate response to antiviral drug treatment.

Phase 1b, Open-label Study of Tune-401 to Assess Safety, PK and PD in Adults With Chronic Hepatitis B

This study will be conducted to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of Tune-401 in adult participants with Chronic Hepatitis B.

The Effectiveness and Safety of TMF in the Treatment of Chronic Hepatitis B Patients With Normal ALT.

This is a multicenter, randomized, open, blank controlled trial ，in order to evaluate the effectiveness and safety of Amibufenamide（TMF） in the treatment of chronic hepatitis B virus infection patients with normal ALT .

Long-term Outcomes of Anti-viral Therapies in Patients With Chronic Viral Hepatitis B

The goal of this observational, multicenter , real-world study is to evaluate the long-term outcomes of different antiviral therapies in adults with chronic hepatitis B (CHB). The main questions it aims to answer are: What is the 5-year incidence of hepatocellular carcinoma (HCC) under various treatment regimens? How do rates of HBsAg seroclearance, decompensated cirrhosis, liver fibrosis progression, and other virological and clinical outcomes compare across regimens? Researchers will compare real-world treatment arms-including nucleos(t)ide analogue (NA) monotherapy (e.g., entecavir, tenofovir), PegIFN based regimen (e.g., PegIFN monotherapy, PegIFN plus NA combinations)-to identify optimal strategies for reducing HCC risk and improving functional cure rates. Participants will undergo routine clinical care with no study-imposed interventions; data on demographics, medical history, symptoms, laboratory tests (e.g., HBsAg, HBV DNA, liver function), imaging (e.g., ultrasound, elastography), and clinical events will be collected prospectively (for up to 5 years in some cohorts) or retrospectively from medical records at baseline and scheduled follow-up visits (e.g., every 3-12 months initially, then annually).

A Randomised Controlled Phase 1 Study of Vaccine Therapy for Control or Cure of Chronic Hepatitis B Virus Infection

This is a pilot study to determine the safety and efficacy of a novel adjuvanted hepatitis B virus (HBV) vaccine formulated as a potential therapeutic vaccine against chronic HBV infection. An ongoing human clinical trial of this HBV vaccine in a prophylactic setting has confirmed this vaccine to be more effective at inducing seroconversion as measured by development of Hepatitis B surface antibody (HBsAb) in poor responder subjects than the standard alum-adjuvanted HBV vaccine, providing promise that this new vaccine may also be able to induce HBV viral control and/or seroconversion in chronically infected subjects

Observation Study on Reducing the Risk of Liver Cancer Associated With Hepatitis B (Zhiyuan) Project.

This study is a multicenter, prospective, observational real-world study designed to investigate and analyze the current treatment patterns of chronic hepatitis B (CHB) across 200 hospitals in China. By comparing patient outcomes under different therapeutic regimens, it aims to provide high-quality evidence-based medical data to optimize CHB treatment strategies and follow-up protocols, ultimately contributing to the advancement of a functional cure for chronic hepatitis B.

A Novel Combination Therapeutic Strategy Aiming to Functional Cure for Chronic Hepatitis B Virus Infection (Sustained HBsAg Loss) (B)

Hepatitis B virus (HBV) infection is a major public health threat in China. At present, a functional cure, also known as clinical cure or sustained Hepatitis B surface antigen (HBsAg) loss, is recommended as the ideal endpoint of HBV treatment. However, HBsAg loss can be achieved in less than 10% of chronic hepatitis B (CHB) patients treated with current available antiviral drug interferon (IFNα) or nucleos(t)ide analogues (NAs) monotherapy. With the support of the national major special funding for infectious diseases from "11th Five-Year Plan" to "13th Five-Year Plan", we have implemented a pioneer clinical study of sequential combination of IFNα therapy on NAs to treat NAs-treated CHB patients (ie. New Switch Study). This is the world's first clinical trial aiming to functional cure, which increased the rate of HBsAg loss to 15% in the overall population in our study, and to 30-50% among those with lower baseline HBsAg levels. How to further improve the HBsAg loss rate is an urgent issue for us. The key point of achieving functional cure is to reverse the HBV-specific T cell exhaustion and establish the long-term immune control against HBV infection. (Programmed death-1) PD-1/programmed death-ligand 1 (PD-L1) axis blockade has been demonstrated to reinvigorate exhausted CD8+ T cells, and would be a potential strategy to treat chronic HBV infection. In this study, a large multicenter prospective study will be performed to explore the safety and efficacy of a novel combination strategy involving immune checkpoint inhibitor (anti-PD-1 antibody) and IFNα in CHB patients, observe the HBsAg loss rate in NA-treated CHB patients receiving this combination strategy, evaluate the potential of breaking immune tolerance by this strategy, and further assess its efficacy to further improve the clinical cure rate on the basis of New Switch Study. Based on New Switch Study, this study further attempts to reverse T cell exhaustion in CHB patients, explore a novel platform of combination therapy development for clinical cure, and ultimately increase the HBsAg loss rate to higher than 50% in overall patients. The implementation of the project is expected to reduce the burden of HBV infection in China and contribute to the goal of global elimination of hepatitis B and C by 2030 (WHO 2030).

A Novel Combination Therapeutic Strategy Aiming to Functional Cure for Chronic Hepatitis B Virus Infection (Sustained HBsAg Loss) (A)

Hepatitis B virus (HBV) infection is a major public health threat in China. At present, a functional cure, also known as clinical cure or sustained Hepatitis B surface antigen (HBsAg) loss, is recommended as the ideal endpoint of HBV treatment. However, HBsAg loss can be achieved in less than 10% of chronic hepatitis B (CHB) patients treated with current available antiviral drug interferon (IFNα) or nucleos(t)ide analogues (NAs) monotherapy. With the support of the national major special funding for infectious diseases from "11th Five-Year Plan" to "13th Five-Year Plan", we have implemented a pioneer clinical study of sequential combination of IFNα therapy on NAs to treat NAs-treated CHB patients (ie. New Switch Study). This is the world's first clinical trial aiming to functional cure, which increased the rate of HBsAg loss to 15% in the overall population in our study, and to 30-50% among those with lower baseline HBsAg levels. How to further improve the HBsAg loss rate is an urgent issue for us. The key point of achieving functional cure is to reverse the HBV-specific T cell exhaustion and establish the long-term immune control against HBV infection. Programmed death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) axis blockade has been demonstrated to reinvigorate exhausted CD8+ T cells, and would be a potential strategy to treat chronic HBV infection. In this study, a large multicenter prospective study will be performed to explore the safety and efficacy of a novel combination strategy involving immune checkpoint inhibitor (anti-PD-1 antibody) in CHB patients, observe the HBsAg loss rate in NA-treated CHB patients receiving this combination strategy, evaluate the potential of breaking immune tolerance by this strategy, and further assess its efficacy to further improve the clinical cure rate on the basis of New Switch Study. Based on New Switch Study, this study further attempts to reverse T cell exhaustion in CHB patients, explore a novel platform of combination therapy development for clinical cure, and ultimately increase the HBsAg loss rate to higher than 50% in overall patients. The implementation of the project is expected to reduce the burden of HBV infection in China and contribute to the goal of global elimination of hepatitis B and C by 2030 (WHO 2030).

Study of Tenofovir Alafenamide in HBV-Infected Pregnant Women

The purpose of this study is to evaluate the pharmacokinetics, efficacy and safety of TAF in HBV-infected pregnant women.

Safety, Tolerability, PK & PD of AB-101 Following Oral Administration in Healthy and CHB Subjects.

This three-part, Phase 1 protocol will be the first clinical study of AB-101. Parts 1 and 2 will be a Phase 1a SAD/MAD of AB-101 in healthy adult subjects. Part 3 will be a Phase 1b dose-ranging assessment of AB-101 in non-cirrhotic Chronic Hepatitis B (CHB) subjects.

HBV-Specific TCR-T Cell Therapy Combined With Nucleos(t)Ide Analogues in Chronic Hepatitis B Patients

This is a open-label study to evaluate the safety and efficacy of autologous T-cells transfected with messenger ribonucleic acid (mRNA) encoding Hepatitis-B virus (HBV) antigen specific T cell receptor (TCR) in combination with nucleos(t)ide analogues (NAs) in HBeAg-positive and negative chronic hepatitis B patients.

A Study to Evaluate the Safety and Immunogenicity of an Investigational Vaccine for Chronic Hepatitis B Virus Infection, in Healthy Adults

The purpose of this first time in humans trial is to evaluate the safety, reactogenicity and immunogenicity of repeated administrations of AVX70371 in healthy participants.

A Real-World Study of Antiviral Therapy in Children With Chronic Hepatitis B

This is a multicenter, prospective, real-world study. The study plans to include a total of 2000 patients who meet the inclusion and exclusion criteria, consisting of 1600 treatment-naive patients and 400 treatment-experienced patients. The effectiveness and safety of different treatment strategies will be evaluated in children aged 1-12 years with treatment-naive and treatment-experienced chronic hepatitis B (CHB) and chronic HBV infection.

Hepatitis Delta Virus Infection: Cross-sectional Study in Patients With Chronic Hepatitis B Virus Infection

The goal of this observational study is to determine the prevalence of hepatitis D virus (HDV) and the distribution of the HDV genotype in patients with chronic hepatitis B infection. It will also identify factors related to hepatitis D virus infection, such as characteristics of the study sample, vaccination history, drug use affecting hepatitis, family factors, environment, and lifestyle. This study will be conducted at Tam Anh General Hospital, Bach Mai Hospital and Tam Anh TP. Ho Chi Minh General Hospital. Participants will be interviewed directly through a questionnaire to collect some information related to epidemiological risk factors. A blood sample will also be collected.

Effects of Peginterferon Consolidation Therapy on Hepatic cccDNA Dynamics in CHB Patients Achieving Clinical Cure.

This is a single-center, prospective, exploratory clinical study. The study plans to enroll 30 chronic hepatitis B (CHB) patients which achieved HBsAg clearance based peginterferon α-2b treatment. Eligible subjects will receive either 12-24 weeks interferon consolidation therapy (180μg administered subcutaneously in the abdomen or thigh once weekly) or not according to physician's recommendation and patient's preference, with regular follow-up for HBV recurrence. Patients will be followed up every 12 weeks. The study will evaluate changes in intrahepatic covalently closed circular DNA (cccDNA) and peripheral blood HBV pregenomic RNA (pgRNA) levels after achieving HBsAg clearance.

A Study of LP-128 Capsules in Healthy Subjects

A Randomized, Double-blind, Placebo-controlled Study to Evaluate Safety, Tolerability and Pharmacokinetics of LP-128 Capsules After Single- and Multiple-Dose in Healthy Subjects

From Fungus to Virus, Investigating the Safety and Efficacy of Terbinafine in Chronic Hepatitis B Patients

Rationale: Currently, there is no curative therapy available for patients that are chronically infected with the hepatitis B virus (HBV). Especially the presence of a viral reservoir of stable episomal, covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocytes poses a great challenge for the development of curative therapies. HBV cccDNA acts as the template for production of viral proteins and HBV genomes. In a preclinical study, terbinafine (an antifungal agent) was identified as a potent and specific suppressor of HBx-mediated cccDNA transcription. HBx is an accessory viral protein of HBV which has been proven to be essential for HBV replication and enhances replication at the transcriptional level in vivo. The suppression of cccDNA transcription results in a strong reduction of the production of viral genomes (RNA and DNA) as well as viral proteins. This will allow recovery of the immune system, increase viral clearance and prevent replenishment of the cccDNA pool in the hepatocyte, all contributing to cure chronic hepatitis B (CHB). Objective: to provide proof of concept for the inhibition of HBx mediated cccDNA transcription by terbinafine, both as monotherapy and add-on therapy next to tenofovir. Secondary outcomes will be the safety and tolerability of terbinafine in this specific group. Study design: This pilot study is a stratified, single center, randomized, double-blinded, placebo-controlled, dose-ascending proof of concept clinical trial. Study population: patients chronically infected with the hepatitis B virus with a normal liver function and no signs of liver damage, who do not use any antiviral medication (group A, n=16) or are treated with tenofovir \> 6 months (group B, n=16). Intervention: Patients will be randomly allocated to daily oral treatment with terbinafine or a matched placebo, either as monotherapy (group A) or as add-on therapy to tenofovir (group B). Main study parameters/endpoints: Primary outcomes: decline in level of serum HBsAg \>0.32log10 IU/mL in both groups A and B and decline in serum HBV DNA \>0.86log10 in group A at the end of study treatment (week 10 vs baseline). Secondary outcomes: 1) Safety and tolerability of terbinafine as mono- or combination therapy; 2) level of serum HBsAg and HBV DNA at 3 months follow-up; 3) decline of HBsAg levels over time (all visits); 4) HBV RNA, large HBsAg (LHBs) HBcrAg levels, and HBeAg status at baseline and end of study 4). Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Patients participating in this study will undergo physical examinations and blood sample collections (13 samples and in total 467.5 mL). They will also be asked to fill in the HBQOL and EQ5D5L quality of life questionnaires and a medicine diary. In total there will be 13 visits in the hospital of which 7 will be for blood collection only. Terbinafine can induce liver damage 1 of 50,000 to 120,000 prescriptions (LiverTox), a weekly safety laboratory control is implemented in the visits to detect possible liver toxicity in an early stage and prevent liver damage.

Research on Clinical Recovery and Maintenance Strategies for CHB

Collect basic information of patients before antiviral treatment and when HBsAg disappears, and divide them into three groups A, B, and C based on baseline anti HBs titers after informed consent. During the follow-up period of all patients, clinical biochemistry, virology (HBVDNA, HBVRNA), serological indicators (HBsAg, anti HBs, HBeAg, anti HBe, HBcrAg, anti HBc), AFP, Fibroscan, liver imaging examinations will be conducted every 3-6 months, and blood samples will be retained for monitoring the frequency of immune cells (pDC, Treg) and the expression of functional molecules, as well as cytokines (IFN - γ, IP-10, IL-10, and TGF - β). Observe the sustained response rate and recurrence rate of virological and serological indicators, as well as the incidence of hepatitis and liver cancer during the follow-up period.

Clinical Study of Antiviral Therapy Combined With Novel Immunotherapy for CHB in Adults

Establish a study cohort of adult chronic hepatitis B antiviral treatment based on the principle of responseguidedtreatment (RGT) corresponding to the child cohort, analyze the clinical cure factors of IC and IT stage adults chronic hepatitis B, and optimize the antiviral treatment plan. To determine the safety and efficacy of PD-1 antibody combined with Peg-FNa-2b in the treatment of adult NAs patients with CHB advantage.

Effectiveness of TAF in Reducing Clinical Events in CHB Patients Beyond Treatment Indications by Current Guidelines

Treatment with Tenofovir Alafenamide(TAF) in Chronic Hepatitis B (CHB) patients classified as beyond treatment indication of current international guidelines (e.g. aged more than 40 years old and 4 ≤ log HBV-DNA IU/mL \< 8) is expected to bring improvement in long-term clinical outcomes. This expected result may expand the treatment indications in patients with CHB based on age and HBV-DNA in contrast to current international guidelines of CHB.