Viral Infection

Researchers are studying chronic liver diseases and tumors, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), cirrhosis, and hepatocellular carcinoma (HCC). These conditions can be caused by viral infections like hepatitis B, C, and D or lifestyle factors such as overeating and lack of exercise. The goal is to develop better understanding and new treatments by analyzing liver tissues and tumors at the single-cell level to identify therapeutic targets and improve patient outcomes. The study involves creating patient-derived preclinical models, such as spheroid cultures and mouse xenograft models, to test new treatment strategies. Blood samples and tissue biopsies are collected during surgeries, biopsies, or diagnostic tests. Researchers use advanced molecular techniques like single-cell RNA sequencing to examine tumor heterogeneity and the liver environment, aiming to discover new biomarkers and treatment predictors. Participants will undergo procedures as part of their care, including hepato-bilio-pancreatic surgery, biopsies, or locoregional treatments. Blood samples are taken during these procedures to support research. Researchers will monitor surgery outcomes over an average of eight years. By studying patient samples and clinical data, the team aims to improve personalized medicine approaches and identify new preventive and therapeutic targets for chronic liver diseases and liver cancer.

This research aims to evaluate whether creating dedicated HIV teams in hospitals across ten European countries can increase HIV testing rates among patients showing signs of HIV-related conditions. The study uses a stepped-wedge design, where hospitals switch from routine care to the new intervention in sequence. This approach compares outcomes before and after the teams are in place, helping to understand the impact of the intervention across various locations and medical specialties. The intervention involves establishing local HIV teams led by specialists and supported by nurses and data experts. These teams identify patients needing HIV tests through electronic health records, provide feedback to doctors to encourage testing, offer education to healthcare staff about HIV, reduce stigma, and improve connections to prevention and care services. This program integrates smoothly into regular hospital routines and aims to close gaps in HIV diagnosis. Participants' HIV testing rates will be monitored by reviewing records before and after the intervention. Researchers will also assess new HIV diagnoses, changes in testing patterns by country and specialty, and healthcare professionals' knowledge and attitudes toward HIV. The study includes ongoing evaluation of how well the teams operate, resource use, and cost-effectiveness. Data collection extends up to several years to observe long-term effects, with continuous monitoring of care access and prevention services.

Researchers are studying HIV-1 infected adults who are currently on a stable triple drug regimen to see how switching to a dual therapy affects the virus and immune system. This trial compares dual therapy with dolutegravir and lamivudine (DTG/3TC, Dovato) against a triple regimen with bictegravir, tenofovir alafenamide, and emtricitabine (BIC/TAF/FTC, Biktarvy). The main goal is to check if the dual therapy is not worse than the triple therapy in terms of the amount of intact HIV virus in blood cells after 48 weeks, while monitoring immune activation and inflammation markers. Participants will be randomly assigned to either continue their triple therapy or to switch to dual therapy. The study includes a 48-week primary period and extends up to 240 weeks to assess longer-term effects. Researchers will measure viral sequences, immune system markers, metabolic health indicators like weight and insulin resistance, and body composition using scans such as DXA and FibroScan. Patient experiences will also be evaluated through questionnaires. During the study, participants will attend regular visits for blood sample collection and assessments of viral load, immune function, metabolic health, and liver condition. These include measuring markers like interleukin-6, C-reactive protein, T cell activation and exhaustion indicators, and others. The study aims to ensure safety and monitor any health complications over nearly five years. Participants must agree to ongoing blood sample storage for research and complete scheduled assessments throughout the study.

Researchers are studying patients with severe pneumonia admitted to the Respiratory Intensive Care Unit (RICU) to understand the epidemiology and clinical characteristics of pneumonia caused by various factors. This observational cohort study aims to gather detailed clinical data including morbidity, mortality, risk factors, symptoms, and radiographic changes to help improve clinical care for severe pneumonia patients. The study involves patients admitted to the RICU due to pneumonia from any cause. There are no specific treatments or interventions being tested, as this is an observational study collecting data during the patients' stay. Researchers will observe respiratory support parameters, treatment options, and symptom developments during the initial days and weeks of hospitalization. Participants will be monitored for outcomes such as mortality and morbidity during their time in the RICU, with measurements taken over one year. Data on symptoms within the first 48 hours, respiratory support during the first 5 days, and treatments over 3 weeks will be collected. The study records clinical information to better understand pneumonia in this critical care setting, with participant involvement lasting as long as their hospital stay and follow-up for outcomes.

Researchers are evaluating molnupiravir, a study medicine designed to stop the COVID-19 virus from multiplying, to see if it can prevent severe illness from COVID-19 in adults who are at high risk. This trial focuses on people who may not be able to take certain other COVID-19 treatments due to availability or potential drug interactions. The study aims to compare molnupiravir with a placebo to understand if it reduces hospitalization, death, or medically attended visits related to COVID-19. Participants are randomly assigned to receive either 800 mg of molnupiravir or a matching placebo orally every 12 hours for 5 days, totaling 10 doses. Some participants may also receive remdesivir as part of standard care if it is clinically appropriate and available. The study is double-blind, meaning neither participants nor researchers know who receives the active drug or placebo. During the study, participants will be monitored for up to 29 days to track hospitalizations, deaths, and adverse events. Researchers will assess symptoms, viral levels, and any medical interventions related to COVID-19. Safety will be followed for approximately five months, including any side effects or reasons for stopping the study treatment. The total time commitment varies, with regular assessments and monitoring to understand the treatment's effects and safety.

Researchers are studying a new treatment approach for patients with surgically removable head and neck squamous cell carcinoma (HNSCC), a common and serious type of cancer in the head and neck region. The study evaluates the safety and tolerability of combining immune-targeted therapy with a lysogenic herpes simplex virus (HSV) as a neoadjuvant treatment to reduce tumor size before surgery. This innovative combination aims to improve surgery outcomes and lower the chances of cancer returning or spreading. Participants receive a combination of treatments including Tislelizumab given on days 1 and 22, and continuous daily Afatinib from days 1 to 42. They also receive injections of the lysogenic HSV virus directly into lymph nodes, with dosing based on lymph node size, given twice two weeks apart. After these treatments, patients undergo standard surgical removal of the tumor. The HSV virus injection includes an initial dose-escalation phase followed by a dose-expansion phase to find the most effective dose. During the study, patients are closely monitored for side effects and treatment tolerance, including checking for dose-limiting toxicities during surgery. Researchers will assess how well the tumor responds to treatment by examining major and complete pathological responses and overall tumor shrinkage up to eight weeks after treatment. They will also monitor adverse events for up to 12 weeks and follow disease-free survival for one year. The study duration and procedures are planned to provide detailed information on the safety and effects of this combined therapy.

Researchers are evaluating whether combining HIV-specific broadly neutralizing antibodies (bNAbs) with antiretroviral therapy (ART) in adults newly diagnosed with acute HIV infection (AHI) is safe and can delay viral rebound compared to ART alone. This phase II, randomized, double-blind, placebo-controlled study aims to assess the impact of this combination on viral load, immune response, and viral reservoirs. The study is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). Participants are randomly assigned to receive either a combination of two bNAbs, VRC07-523LS and PGT121.414.LS, given as intravenous infusions once at study entry alongside daily oral ART, or a placebo infusion with daily ART. The study involves several steps, including treatment initiation, analytic treatment interruption, and monitoring phases. The bNAbs are administered intravenously at specific doses over 15 to 60 minutes at enrollment. ART consists of a daily oral tablet containing bictegravir, emtricitabine, and tenofovir alafenamide. During the study, participants attend scheduled visits for safety assessments, blood tests measuring viral load and immune cells, and monitoring for side effects or adverse events. Researchers track the time to viral rebound after stopping ART, changes in immune cell counts, and drug levels in the blood. Participants who meet criteria for restarting ART will do so and continue to be monitored. The total participation includes treatment and follow-up periods, with close observation to evaluate safety and treatment effects up to 24 weeks after ART interruption.

Researchers are evaluating the safety and immune response of an influenza virus split vaccine in adults aged 60 years and older through a randomized, double-blind, controlled phase I clinical trial. The study includes 120 participants divided into three groups to compare an experimental vaccine dose, a control vaccine dose, and a placebo. This research aims to understand how well the vaccine works and its side effects in this age group. Participants receive one injection of either the experimental influenza vaccine (0.7 mL), a control vaccine (0.5 mL), or a placebo, each administered into the upper arm muscle. Forty individuals are randomly assigned to each group in equal proportions. Laboratory tests are performed before vaccination and on the fourth day after vaccination to monitor immune response and safety. During the study, participants are closely monitored for any side effects for up to 30 days, including both expected and unexpected adverse events. Serious side effects are tracked for six months after vaccination. Researchers measure immune responses 30 days post-vaccination by checking antibody levels and rates of immune reaction. The study involves follow-up visits to assess safety and vaccine effectiveness, with participation lasting several months.

Researchers are evaluating a combination of immune-targeted therapy and lysogenic herpes simplex virus (HSV) virotherapy as a neoadjuvant treatment for patients with surgically resectable head and neck squamous cell carcinoma (HNSCC). This study aims to improve surgical success and reduce the risk of recurrence and metastasis by using these therapies before surgery. The trial is a prospective, single-arm study focused on the safety and tolerability of this innovative approach for patients with locally advanced HNSCC without distant metastasis. Participants will receive tislelizumab on days 1 and 22, afatinib daily from days 1 to 42, and injections of lysogenic HSV virus into lymph nodes in two doses spaced two weeks apart. The virus dose will be adjusted based on lymph node size, with a dose-escalation phase followed by a dose-expansion phase using the most effective dose. After these treatments, patients will undergo standard surgery to remove the tumor. During the study, researchers will monitor participants for dose-limiting toxicities during surgery and evaluate responses such as major pathologic response and complete pathologic response. Additional assessments include adverse events up to 12 weeks, objective response rate up to 8 weeks, and one-year disease-free survival. Participants will attend scheduled visits for treatment administration, surgery, and follow-up to assess safety and treatment effects throughout the trial period.

Researchers are conducting a randomized, double-blind, placebo and positive control Phase Ia clinical trial to evaluate the safety, tolerability, and pharmacokinetics of the SIBP-A16 injection in healthy adults aged 18 to 45. The study focuses on understanding how this injection behaves in the body and its safety profile. It involves healthy volunteers without significant medical conditions to ensure reliable results for the Respiratory Syncytial Virus (RSV) research. Participants will be assigned randomly to different groups organized in five queues, with varying doses of SIBP-A16 injection, placebo, or the active comparator Nirsevimab. The injections will be given either intramuscularly or intravenously in single doses across four different dose levels. Each queue undergoes a 14-day safety observation before the next dose level is administered based on safety committee review. During the study, participants will be monitored for adverse events, serious adverse events, and special adverse events of interest from day one up to 361 days after administration. Blood samples will be collected to measure drug levels over time, including peak concentration and time to peak. Various health assessments like physical exams, vital signs, ECGs, chest X-rays, and lab tests will be performed to ensure participant safety and measure outcomes throughout the nearly one-year follow-up.