Clinical Research Directory

"Pregnancy and Viral Infections: Impact on Pregnant Women and Their Children. French Prospective Cohort"

The VIROPREG study is a French prospective multicenter cohort study that aims to assess the impact of viral infections and antiviral treatments received during pregnancy on maternal and child health. The study focuses on both chronic viral infections: human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV)\] and on arbovirus infections. This study aims at investigating the following research questions: * What is the rate of mother-to-child transmission for each virus? * What are the effects of maternal infection on (i) pregnancy outcomes, (ii) the mother's physical and psychological health, and (iii) the fetus' health and development, with a focus on long-term psychomotor development in children born to women living with HIV? * What is the impact of antiretroviral and/or antiviral prophylactic and/or therapeutic treatments administered during pregnancy on maternal and fetal health? Mother-child pairs will be followed from pregnancy through delivery and from birth until the child reaches 7 years of age. Each mother-child pair will be enrolled into one of four cohort groups based on the maternal infection. HIV Cohort: Pregnant women living with HIV who participate in the research will: * Be followed according to the routine care schedule from enrollment to post-natal visit usually scheduled in maternity after delivery (6-8 weeks post-partum) * Participate in additional follow-up by phone call or videoconference at 4- and 7-years post-partum for research purposes * Complete questionnaires at inclusion, delivery, 4- and 7- years postpartum * In case of breastfeeding, receive follow-up care aligned with routine schedules for up to 2 years postpartum, including 2 additional visits specifically for research at 2- and 3- months postpartum. * In selected cases: provide blood, umbilical cord blood, colostrum and breast milk samples during follow-up visits for research purposes (pharmacological and virological analyses). Children born to mothers living with HIV and who participate in the research will: * Be followed according to the routine care schedule from birth until 2 years of age * Participate in additional follow-up by phone call or videoconference, addressed to mothers, at 4- and 7- years of age for research purposes. HBV Cohort: Pregnant HBV-infected women who participate in the research will: * Be followed according to the routine care schedule from enrollment to post-natal visit usually scheduled in maternity after delivery (6- 8 weeks post-partum) * Complete questionnaires at inclusion and delivery * Provide blood samples during follow-up visits for research purposes. Children born to HBV-infected mothers and who participate in the research will: * Be followed according to the routine care schedule from birth to 2 years of age * Participate in additional follow-up for research purposes at 3 months and 18-24 months of age. HCV Cohort: Pregnant HCV-infected women who participate in the research will: * Be followed according to the routine care schedule from enrollment to post-natal visit usually scheduled in maternity after delivery (6 - 8 weeks post-partum) * Complete questionnaires at inclusion and delivery * Provide blood samples during follow-up visits for research purposes. Children born to HCV-infected mothers and who participate in the research will: * Be followed according to the routine care schedule from birth until 2 years of age * Attend additional follow-up visits scheduled at 3 and 9 months of age for research purposes. Arbovirus Cohort: Pregnant women infected with arbovirus who participate in the research will: * Be followed according to the routine care schedule from enrollment to delivery * Participate in additional follow-up for research purposes at 4 years after delivery. * In case of breastfeeding, women will be monitored for research purposes at Day 7 and Day 30 postpartum * Complete questionnaires at inclusion, Day 7-10 from the inclusion, delivery and 4 years after delivery * Provide blood, amniotic fluid, placenta, umbilical cord blood, colostrum and breast milk samples during follow-up visits for research purposes. Children born to mothers infected with arbovirus and who participate in the research will: * Be followed according to the routine care schedule from birth until 2 years of age. * Participate in additional follow-up for research purposes at inclusion, Day 7 and Day 30 after inclusion * Participate in additional follow-up by phone call or videoconference, addressed to mothers, at 4- and 7- years of age for research purposes.

STOP HCC-GAAD-APAC-Thailand

Hepatocellular carcinoma (HCC) surveillance is frequently underutilized, and currently available biomarkers, such as alpha-fetoprotein (AFP), demonstrate suboptimal diagnostic performance. This prospective study aims to evaluate a simplified multivariate index, the GAAD score-comprising gender, age, alpha-fetoprotein (AFP), and protein induced by vitamin K absence or antagonist-II (PIVKA-II)-for its ability to improve the detection of hepatocellular carcinoma in patients with chronic liver disease. The study hypothesizes that incorporation of the GAAD score into standard HCC surveillance strategies will improve diagnostic performance compared with existing surveillance modalities alone and may provide evidence to support its inclusion in future clinical practice guidelines.

Single-cell Multiomics and Spatiotemporal Omics Analyze the Mechanism of Liver Degenerative Disease

The purpose of this observational study is to employ single-cell multi-omics and spatial omics technologies to characterize the spatial and immune structures within the livers of patients with fatty liver, hepatic hemangioma, focal nodular hyperplasia, liver fibrosis, cirrhosis, and HBV infection. The primary questions it aims to address are: Investigate the mechanisms of liver degenerative changes during the processes of liver aging, fatty liver, HBV infection, liver fibrosis, and cirrhosis. Characterize the molecular features and cellular networks at different stages of liver degeneration and identify new targets and mechanisms for the cure of the aforementioned diseases. The study will collect peripheral blood and discarded liver tissue from patients with hepatic hemangioma, fatty liver, HBV infection, liver fibrosis, and cirrhosis who are undergoing hepatectomy or liver biopsy.

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 .

Immune Dynamics in the Natural History of Chronic HBV Infection

The purpose of this observational study is to follow up on chronic HBV-infected patients over a long period of time to understand the changes in the immune status as age increases and the natural history of chronic HBV infection progresses. The main questions it aims to answer are: * Does the natural history of chronic HBV infection progress with changes in HBV-specific immunity? * What is the role of age in the natural history of chronic HBV infection? Patients with chronic HBV infection who are untreated and aged 1-80 years will be followed up every six months. During each follow-up, HBV-related serological and virological indicators will be tested. Peripheral blood samples will also be collected to test HBV-specific immunity and the immune environment.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial to Evaluate the Efficacy and Safety of TVAX-008 Injection in Chronic Hepatitis B Patients

The objective of this study was to evaluate the efficacy and safety of TVAX- 008 injection in a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase II clinical trial in subjects with HBSAg levels of 0.05 to 100 IU/mL, including CHB patients previously treated with siRNA/ASO drugs and treatment-naive HBV infection.

Clinical Trials of the Hepatitis B Sandwich Combination Therapy for Treating Patients Infected With Hepatitis B Virus

* Primary objective: The main objective of this study is to assess the efficacy and safety of a sandwich combination therapy in patients who were infected with HBV or have undergone surgery for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). The primary efficacy endpoints are HBsAg seroconversion rate (HBsAg disappearance and HBsAb appearance), and HCC recurrence rate at week 49. Secondary Objective: To evaluate the safety of the HBV sandwich combination therapy through various safety indicators. Safety Indicators as follows: 1) Vital Signs: Monitoring systolic and diastolic blood pressure, pulse, respiration, and body temperature; 2) Physical Examination: Comprehensive physical assessments during the study; 3) 12-lead Electrocardiogram: Conducted to monitor cardiac health; 4) Clinical Laboratory Tests: Including blood routine, urine routine, blood biochemistry (focusing on liver and kidney function), coagulation function; 5) Injection Site Reactions: Monitoring for any local adverse effects from injections; 6) Adverse Events (AEs) and Serious Adverse Events (SAEs): Documentation of any AEs or SAEs occurring during treatment. * Study Design: This study comprises three distinct stages: 1. Screening Period (Weeks -4 to -1): 1) Informed consent will be obtained from participants; 2) Collect baseline data and perform various assessments which include: a) 12-lead ECG; b) Infectious disease screening; c) Blood biochemistry, routine blood, urine routine, coagulation function; d) Blood pregnancy test (for female subjects); e) Hepatitis B virus and serology examination; f) Antinuclear antibody testing; g) Imaging examinations. 2. Treatment Period (Weeks 1 to 25): 1) Patients will receive ongoing nucleoside analogue treatment (NAs) throughout this stage; 2) Administer subcutaneous injections of the HBV monoclonal antibody HT-102 weekly for a total of 4 weeks (300 mg each time); 3) After treatment with HT-102, HBV serological and virological assessments will occur; 4) If serum HBsAg is below 10 IU/mL, proceed with therapeutic hepatitis B vaccine FD-001 (60 µg each time) every 4 weeks for a total of 6 doses; 5) If HBsAg is not below 10 IU/mL post HT-102, participants will enter the follow-up period directly. 3. Follow-up Phase (Weeks 25 to 49): 1) Continue with original nucleoside analogue treatment for HBV; 2) Conduct follow-up visits every 12 weeks; 3) Each visit will involve recording vital signs, conducting physical examinations, ECG, laboratory tests (as noted in safety indicators), and testing for HBV and immunological parameters. * End of Study: The study concludes once the follow-up of the last enrolled subject is completed, analyzing the collected data to evaluate efficacy and safety endpoints. \- Note: Careful monitoring and adherence to protocols will be maintained to ensure participant safety and integrity of study data.

"HBV unIversal vs Point-Of-Care-based Antiviral treatMent to Prevent Mother-to-child Transmission"

To achieve global elimination of hepatitis B virus (HBV), it is crucial to eliminate HBV mother-to-child transmission (MTCT) by ensuring high coverage of birth dose vaccine and expanding the adoption of peripartum antiviral prophylaxis (PAP) by tenofovir. Current international guidelines require hepatitis B surface antigen (HBsAg)-positive pregnant women to undergo viral load (VL) quantification to identify those at high risk (VL ≥200,000 IU/mL) who should receive PAP. However, VL testing remains inaccessible in many low- and middle-income countries (LMICs), particularly in rural areas. Consequently, in the forthcoming guidelines, the WHO is going to issue a conditional recommendation for administering PAP to all HBsAg-positive women lacking access to VL testing. Although this universal strategy may appear promising for simplifying the diagnostic process, it may result in overtreating the majority of HBsAg-positive pregnant women, estimated at 85% in Africa and 70% in Asia, for whom birth dose vaccine is likely sufficient. Moreover, the real-world applicability of this strategy in LMICs has never been formally tested. As an innovative alternative, the adoption of a rapid point-of-care test for hepatitis B core-related antigen (HBcrAg-RDT) is proposed to identify women eligible for PAP.This test requires only a drop of capillary blood, eliminating the need for electricity or centrifugation, and can provide a reliable result within 45 minutes. Compared to the universal strategy, HBcrAg-RDT strategy is expected to be less expensive and could prevent unnecessary tenofovir exposure for both women and their fetuses. Our aim is to establish the non-inferiority of the HBcrAg-RDT strategy, in comparison to the universal strategy, in terms of effectiveness, defined as the reduction in maternal VL at the time of childbirth, a main driver of the MTCT risk. This will be approached through a multidisciplinary framework integrating health economics, implementation science, and health policy analysis.