Clinical Research Directory

Targeting ANKRD11 Reverses HBV-Specific CD8+ T Cell Dysfunction and Tolerance

Achieving a functional cure for chronic hepatitis B (CHB) is largely hindered by the irreversible functional exhaustion and immune tolerance of hepatitis B virus (HBV)-specific CD8 positive T (CD8+ T) cells. In investigators previous studies, an in vivo Clustered Regularly Interspaced Short Palindromic Repeat(CRISPR) screen identified ANKRD11 for the first time as an "epigenetic brake" on CD8+ T-cell effector function. Loss of ANKRD11 markedly enhanced the expansion, effector function, and viral clearance capacity of HBV-specific T cells. Based on these findings, investigators hypothesize that ANKRD11 regulates the epigenetic program of T-cell exhaustion by restricting the activity of AP-1 family transcription factors, and that targeting ANKRD11 can reverse T-cell dysfunction and overcome immune tolerance. This project will: (1) elucidate the epigenetic mechanisms by which ANKRD11 regulates T-cell exhaustion using conditional knockout mouse models and multi-omics approaches; (2) evaluate how ANKRD11 deficiency reshapes the differentiation trajectory and antiviral function of HBV-specific T cells in models of chronic HBV infection; and (3) develop a combinatorial gene-editing strategy integrating "release of the brake" with "stepping on the accelerator" to generate enhanced T Cell Receptor-T cell Therapy(TCR-T) cells and evaluate their efficacy and safety in humanized mouse models. The study is expected to define a novel mechanism by which ANKRD11 regulates T-cell exhaustion, establish an enhanced TCR-T therapeutic strategy, and provide a potential approach toward achieving a functional cure for chronic HBV infection.

Dose-Escalation Prime/Boost Therapeutic Vaccination Study Of 2 Chimp Adenoviral Vectors in Adults With Chronic HBV On Nucleos(t)Ide Therapy

This Phase 1b clinical study is a multi-center, open-label, dose escalation, prime only, and prime plus boost therapeutic vaccination study of 2 distinct chimpanzee adenoviral vectors (AdC6 and AdC7), containing parts of hepatitis B virus (HBV) core and polymerase antigens fused within glycoprotein D in a cohort of chronic hepatitis B (CHB)-infected adult participants who are currently receiving entecavir, tenofovir (tenofovir alafenamide fumarate or tenofovir disoproxil fumarate), or lamivudine, with documented HBV viral load suppression for at least 12 months. Approximately 24 participants will be enrolled in Group 1 and randomized to Cohort 1a or Cohort 1b. Those assigned to Cohort 1a will receive a low dose prime therapeutic vaccination of vector AdC7 on Day 1, followed by a booster vaccination on Day 91 using vector AdC6. Those assigned to Cohort 1b will receive a low dose prime therapeutic vaccination of vector AdC6 on Day 1, and will not receive a booster vaccination. Group 2 will then enroll approximately 24 participants randomized to Cohort 2a or Cohort 2b. Those assigned to Cohort 2a will receive a high dose prime therapeutic vaccination of vector AdC7 on Day 1, followed by a booster vaccination on Day 91 using vector AdC6. Those assigned to Cohort 2b will receive a high dose prime therapeutic vaccination of vector AdC6 on Day 1, and will not receive a booster vaccination. Group 3 will enroll approximately 8 participants randomized into Cohort 3a or Cohort 3b. Cohort 3a will receive the high dose prime VRON-0200 vaccination of vector AdC7 on Day 1, followed by doses of VIR-2218 plus VIR-3434 on Days 28, 56, 84, 112, 140 and 168, and then a booster using a high dose VRON-0200 vaccination of vector AdC6 on Day 196. Cohort 3b will receive the same high dose prime VRON-0200 vaccination of vector AdC7 followed by 6 doses of VIR-2218 plus VIR-3434 at the same timepoints as Cohort 3a, but will not receive the booster dose on Day 196. VRON-0200 vaccine doses will be administered by intramuscular (IM) injection. VIR-2218 and VIR-3434 will be administered subcutaneously. All study participants will be followed for a total of 1 year post-prime vaccination.

VIR-2218 and Peginterferon Alfa-2a for Chronic Hepatitis B

Background: Chronic hepatitis B virus (HBV) infection affects 292 million people worldwide; 887,000 die each year from cirrhosis, liver cancer, and related issues. Treatment options are limited. Objective: To test 2 drugs (VIR-2218 and peginterferon) in people with mild or inactive HBV infection. Eligibility: People aged 18 to 65 years with mild or inactive HBV infection. Design: Participants will be screened. They will have blood tests and an eye exam. They will have imaging scans of the liver to check the health of the liver. Participants will be in the study for over 2 years. VIR-2218 is an injection given under the skin of the stomach, upper arm, or thigh. Participants will come to the clinic to receive this injection once a month for 6 months. Peginterferon is also injected under the skin. Participants will have this shot once a week for 6 months. They may either inject themselves at home or come to the clinic to get the injections. Participants will get just the VIR-2218 for 3 months, then both shots for 3 months, then just the peginterferon for 3 months. Participants will have two 3-day stays in the hospital. Tests will include: Liver biopsy. A sample of tissue will be taken from their liver. After the procedure, participants will lie on their right side for 2 hours and then on their back for 4 hours. Fine needle aspiration. A small needle will be used to collect cells from the liver. After the last injection of peginterferon, follow-up visits will continue in the outpatient clinic every 4 to 12 weeks.

Long-term Follow-up Study to Evaluate Participants With Chronic Hepatitis B (CHB) Previously Treated With AHB-137 Injection

This study is a prospective, open-label, multicenter long-term follow-up study to evaluate the durability of virologic response in subjects with chronic hepatitis B previously treated with AHB-137 injection.

A Study to Evaluate the Antiviral Activity and Immune Response of AHB-137 Injection in Participants With Chronic Hepatitis B (CHB)

This study is a single-center, open-label Phase II clinical study to evaluate the antiviral activity and immune responses of AHB-137 injection in participants with CHB treated with nucleos (t) ide analogues.

A Study to Evaluate the Efficacy and Safety of AHB-137 Injection in Participants With Chronic Hepatitis B (CHB)

This is an open-label, multicenter, Phase 2 study designed to evaluate the efficacy and safety of AHB-137 injection in participants with chronic hepatitis B (CHB) with low hepatitis B surface antigen (HBsAg) levels.

A Study of BW-20507 in Chinese Healthy Subjects and Subjects With Chronic Hepatitis B

Phase 1 Study of BW-20507 in Healthy Subjects and Patients With Chronic Hepatitis B. Ia involved a single ascending dose study where healthy participants were administered one dose of BW-20507 or placebo subcutaneously. Ib involved a multiple ascending dose study where participants with chronic hepatitis B virus infection were administered with multiple doses of BW-20507 SC

Study to Evaluate the Efficacy and Safety of AHB-137 in Treatment-naive Participants With Chronic Hepatitis B (CHB)

The study is to evaluate the efficacy and safety of AHB-137 in CHB participants. The total duration of the study, including screening phase, treatment phase and follow-up phase.

A Clinical Study Evaluating the Pharmacokinetic Characteristics and Safety of AHB-137 Injection in Participants With Mild to Moderate Liver Dysfunction and Those With Normal Liver Function.

A clinical study evaluating the pharmacokinetic characteristics and safety of AHB-137 injection in participants with mild to moderate liver dysfunction and those with normal liver function.

A Study to Evaluate AHB-137 Injection in Treatment-naïve Participants With Chronic Hepatitis B

This study is a randomized, double-blind, placebo-controlled, multicenter phase 2 study to assess the efficacy and safety of AHB-137 injection in treatment-naïve participants with chronic hepatitis B.

Follow-up of Chronic Hepatitis B Patients With Comorbid Nonalcoholic Fatty Liver Disease

The purpose of this study is to determine the disease progression in CHB/NAFLD compared with CHB and NAFLD including liver cirrhosis, cirrhotic complications and hepatocellular carcinoma (HCC).

A Multicenter Study of AHB-137 Injection Combined With Other Hepatitis B Drugs

This is a randomized, open-label, multicenter phase II study to evaluate the efficacy and safety of AHB-137 injection in combination with other hepatitis B drugs in participants with HBeAg-negative CHB treated with NAs.

Analysis of Clinical Characteristics of Chronic Hepatitis B Combined With MAFLD in Different TCM Syndrome Types

This is a retrospective cross-sectional observational clinical study. We will collect clinical medical records of patients diagnosed with chronic hepatitis B combined with metabolic associated fatty liver disease who received treatment at Foshan Hospital of Traditional Chinese Medicine. The main purpose is to explore the characteristics of renal function related indicators in these patients, analyze the influencing factors of early renal tubular injury caused by long-term antiviral therapy, and summarize the clinical correlation between liver metabolic abnormalities and early kidney damage. No additional invasive examinations or intervention measures will be performed on patients; only existing historical inpatient and outpatient medical data will be sorted out and statistically analyzed. All personal privacy information of subjects will be strictly desensitized and protected throughout the study

Study of GST-HG131&141 Tablets Compared With Placebo in Patients With Chronic Hepatitis B

A randomized, double-blind, placebo-controlled Phase IIa clinical study to evaluate the safety and efficacy of GST-HG131/GST-HG141 tablets in patients with chronic hepatitis B

Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants With Chronic Hepatitis B (B-Well 1)

This study is intended to confirm the efficacy, safety, pharmacokinetic (PK) profile, and the durability of hepatitis B virus surface antigen (HBsAg) suppression observed with bepirovirsen for 24 weeks (with loading doses) as compared to the placebo arm. This study will have 4 stages: a) Double-blind treatment (bepirovirsen or placebo) for 24 weeks. b) Nucleos(t)ide analogue (NA) treatment for 24 weeks. c) NA cessation stage OR Continue NA for 24 weeks. d) Durability of response and follow up for further 24 weeks for participants who stopped NA treatment at Week 48. The arms will be stratified based on HBsAg level (HBsAg greater than or equal to \[≥\] 100 international unit per milliliter \[IU/mL\] to less than or equal \[≤\]1000 IU/mL or greater than \[\>\] 1000 IU/mL to ≤3000 IU/mL) at screening. The total duration of the study, including screening (up to 60 days), the double-blind treatment stage (24 weeks), the On NA only stage (24 weeks), and the NA cessation and durability stages (48 weeks) is up to approximately 104 weeks at maximum for each participant.

Study of Bepirovirsen in Nucleos(t)Ide Analogue-treated Participants With Chronic Hepatitis B (B-Well 2)

This study is intended to confirm the efficacy, safety, pharmacokinetic (PK) profile, and the durability of hepatitis B virus surface antigen (HBsAg) suppression observed with bepirovirsen for 24 weeks (with loading doses) as compared to the placebo arm. This study will have 4 stages: a) Double-blind treatment (bepirovirsen or placebo) for 24 weeks. b) Nucleos(t)ide analogue (NA) treatment for 24 weeks. c) NA cessation stage OR Continue NA for 24 weeks. d) Durability of response and follow up for further 24 weeks for participants who stopped NA treatment at Week 48. The arms will be stratified based on HBsAg level (HBsAg greater than or equal to \[≥\] 100 international unit per milliliter \[IU/mL\] to less than or equal \[≤\]1000 IU/mL or greater than \[\>\] 1000 IU/mL to ≤3000 IU/mL) at screening. The total duration of the study, including screening (up to 60 days), the double-blind treatment stage (24 weeks), the On NA only stage (24 weeks), and the NA cessation and durability stages (48 weeks) is up to approximately 104 weeks at maximum for each participant.

Study of Tenofovir Alafenamide (TAF) in Children and Teen Participants With Chronic Hepatitis B Virus Infection

The goals of this clinical study are to compare the effectiveness, safety and tolerability of study drug, tenofovir alafenamide (TAF), versus placebo in teens and children with CHB and to learn more about the dosing levels in children.

TherVacB - A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate

This study is an open-label, ascending dose phase 1b/2a trial to assess the safety and immunogenicity of a heterologous protein prime/MVA boost therapeutic hepatitis B vaccine in patients with chronic HBV who are virally suppressed with oral anti-viral therapies.

A Heterologous Protein Prime/MVA Boost Therapeutic Hepatitis B Vaccine Candidate

This study is an open-label, ascending dose phase 1a trial to assess the safety and immunogenicity of a heterologous protein prime/MVA boost therapeutic hepatitis B vaccine

Assessment of Treatment Adherence and Associated Factors in Chronic HepB Patients Supported by HBVCare

Adherence to chronic Hepatitis B (HBV) treatment and regular follow-up visits is essential for preventing dangerous complications, yet adherence rates in Vietnam remain low due to barriers in patient awareness and geographic conditions. Digital health solutions, particularly mobile applications, have shown potential as tools for supporting patients in proactive disease management. The HBVCare mobile application was developed to provide features such as medication reminders, storage of lab results, and health education to improve treatment adherence and clinical outcomes. The investigators are conducting a multicenter, randomized controlled trial at Hoang Long Clinic and Hanoi Medical University Hospital to evaluate the effectiveness of HBVCare. Patients are randomized into either a control group receiving standard care and an intervention group using the HBVCare app, with patient adherence and related factors assessed after three months of treatment.

Study of AHB-137 in Participants With Chronic Hepatitis B (CHB) Treated With Nucleos(t)Ide Analogues (NAs)(AUSHINE)

This study is a randomized, double-blind, multicenter phase 3 clinical trial to evaluate the efficacy and safety of AHB-137 injection in participants with HBeAg-negative CHB treated with NAs.

Tenofovir Alafenamide Switching Therapy in Kidney or Liver Transplant Recipients With Chronic HBV Infection

tenofovir alafenamide (TAF) has been approved to be highly effective and safe in patients with chronic hepatitis B (CHB), therefore TAF may be a good option in kidney or liver transplant patients with chronic HBV infection. The aim of this prospective cohort study is to assess the safety, efficacy, and drug adherence improvement of TAF switching therapy in kidney or liver transplant patients with HBV infection.

Efficacy of VTP-300 in Chronic Hepatitis B Infection

This is an open-label study to determine the efficacy, safety, tolerability and immunogenicity of ChAdOx1-HBV and MVA-HBV, together VTP-300, in combination with low-dose nivolumab, in patients with chronic HBV who are virally suppressed with oral anti-viral therapies.

Union-FAST: An Intelligent-Agent Intervention to Increase Antiviral Treatment Uptake in Diagnosed-but-Untreated Hepatitis B Patients

The World Health Organization (WHO) has set a target to eliminate viral hepatitis by 2030, aiming for a 90% diagnosis rate and an 80% treatment rate for chronic hepatitis B (CHB). However, as of 2024, only 26.1% of CHB infections globally have been diagnosed, and only 14.6% have received treatment, with treatment coverage falling far short of the target. A large number of patients are in a "Diagnosed-but-Untreated (DBU)" state, with major barriers including: low disease awareness, concerns about medication side effects, fragmented healthcare pathways, and poor physician-patient communication. Traditional hospital-based follow-up models are constrained by human resources and the capacity for health information system integration, making them difficult to scale widely in primary care settings. Supported by the National Key R\&D Program of China, our team has successfully developed the world's first infectious disease agent (Union-Agent) after more than two years of research. This study aims to conduct a multicenter, prospective, two-cohort observational and interventional investigation to identify the reasons why DBU patients fail to initiate treatment and to explore whether an intervention using the Union-Agent can significantly increase the rate of antiviral treatment initiation within six months among DBU patients who meet the antiviral indications according to the 2022 Chinese guidelines for the prevention and treatment of chronic hepatitis B. The study hypothesizes that, compared to baseline, the Union-Agent can enable 50%-60% of treatment-eligible DBU patients to initiate antiviral therapy within six months.