Dengue Fever

This research aims to develop a safe controlled human infection model for dengue fever using an attenuated dengue virus serotype 3 (DEN3) in adult volunteers aged 21 to 45 years. It will analyze the clinical, viral, and immune responses to better understand dengue fever's pathophysiology. The study is designed to establish a reproducible infection in at least 80% of participants and to provide data to support future vaccine and treatment studies, including a planned follow-up dengue vaccine efficacy trial. Participants will receive a subcutaneous injection of a GMP-produced rDEN3delta30 virus, which is an attenuated form of the dengue virus developed by the National Institutes of Health. The study will monitor infection and immune responses in detail, including clinical symptoms, blood tests, and immune profiling. The challenge virus dose and safety protocols are based on prior studies conducted in the US. The study includes a quarantine period and follow-up evaluations to track viral kinetics and immune markers. During the study, participants will undergo regular clinical assessments, laboratory tests including blood samples, and safety monitoring from the day of viral challenge through at least 28 days post-inoculation, with longer-term immune response follow-up lasting up to three years. Researchers will measure occurrence and severity of adverse events, infection rates, viral load, symptom severity, and immune responses. The study requires contraception use during and after the trial for safety. Participation involves quarantine and multiple visits to collect data on dengue infection and immune responses.

Researchers are evaluating the safety, tolerability, and how the body processes (pharmacokinetics) single and multiple intravenous doses of a drug called BWC0977 in healthy adult volunteers. This Phase 1 study involves a total of 64 healthy adults aged 18 to 55 years and is designed as a randomized, double-blind, placebo-controlled trial with multiple dose groups. The study focuses on measuring any treatment-emergent adverse events and serious adverse events to understand the drug's safety profile. Participants will be divided into two main groups: single ascending dose (SAD) and multiple ascending dose (MAD) cohorts. In the SAD phase, volunteers receive one intravenous infusion of BWC0977 or placebo over 2 hours at doses of 750 mg or 1500 mg. In the MAD phase, participants receive multiple intravenous infusions of BWC0977 or placebo over 30 minutes to 2 hours daily for 7 to 10 consecutive days. Dose levels will increase sequentially based on safety and tolerability data collected during the study. During the study, participants will undergo various assessments including physical exams, vital signs, ECGs, laboratory tests, and blood sampling at specific times before, during, and after infusions to monitor safety and measure drug levels in the body. Researchers will track adverse events for up to 8 days after single dosing and up to 16 days after multiple dosing. Volunteers must comply with study visits and requirements throughout the trial, which lasts until August 2026.

Researchers are investigating whether adding a rapid biomarker test to current clinical guidelines can better identify young children with fever who are at risk of serious infections in sub-Saharan Africa. This study compares standard care based on integrated management of childhood illness (IMCI) guidelines alone to an approach enhanced by measuring suPAR levels, a biomarker, during the first clinical assessment. The goal is to see if this combined strategy improves decisions about hospital admission or discharge and leads to better health outcomes for children aged 2 to under 60 months. The trial is a multi-country, open-label, randomized study with two groups: one receiving the standard IMCI-based care and the other receiving IMCI care plus a point-of-care suPAR test. Blood samples will be taken from all children, but only the intervention group will have their suPAR levels measured immediately. Clinicians will use these results along with IMCI guidelines to decide whether to admit or discharge each child during the first clinical visit. A second, more detailed clinical assessment will also be performed on all participants to confirm or adjust decisions and ensure safety. Children will be followed up on days 3 and 7 after enrollment with additional visits if clinical worsening occurs. A day 28 follow-up will collect information on serious events, hospitalizations, or deaths, with an optional extra interview at three months. Participants with respiratory symptoms may join a substudy involving lung exams and sample collections. The study team will measure outcomes like the appropriateness of discharge decisions, hospital admissions, severity of illness, and mortality to evaluate the new triage approach's effectiveness and safety over these timeframes.

Researchers are studying the effectiveness of a tetravalent dengue vaccine (TDV) in reducing hospital stays due to dengue in children and adolescents aged 6 to 12 years living in Southeast Asian countries with high dengue transmission, including Thailand, Indonesia, and Malaysia. This observational study focuses on participants in a community-based cohort who may or may not receive the vaccine as part of a pilot public vaccination program where TDV is already approved. The study particularly aims to assess the vaccine's effectiveness against less common dengue virus types DENV-3 and DENV-4. The study includes a nested case-control design with two groups: cases who are hospitalized children or adolescents with confirmed dengue infection, and matched controls who live in the same neighborhood but have not been hospitalized with dengue. Participants are followed individually for up to 3 years within the cohort. The study is non-interventional, observing outcomes based on vaccination status within the existing vaccination program. Participants will be monitored through active hospital surveillance to identify dengue hospitalizations confirmed by laboratory testing. Data collected includes blood samples for RT-PCR testing, clinical diagnosis, and hospitalization records. Researchers will measure the rate of hospitalization due to dengue virus infections by serotype and baseline dengue immune status. The primary outcome is dengue-related hospitalization up to 36 months. Parents or legal representatives provide consent and assent for participants, including agreement for blood sample collection and follow-up over the study period.

Researchers are evaluating the safety and immune response of the Dengue Tetravalent Vaccine (TDV) in children younger than 2 years old. This Phase 3 randomized, double-blind, placebo-controlled trial focuses on infants and toddlers aged 6 to 20 months to understand how well the vaccine activates their immune systems and its safety profile. The study aims to provide detailed information about vaccination with TDV in this young age group. Participants will be divided into groups based on age: 6 to <12 months and 12 to <21 months. Each group will receive two doses of either the TDV vaccine or a placebo (normal saline) injected subcutaneously on Day 1 and Day 90. The study follows an age-descending design, and both vaccinations and placebo injections are administered within the routine vaccination schedule. During the trial, participants will visit the clinic eight times for vaccinations, blood draws, and health checks. Blood samples are collected before vaccination and at several points afterward to assess immune response. Researchers will monitor local and systemic adverse events, medically attended events, and serious adverse events throughout the study, which lasts up to approximately three years. The main outcomes include safety within days after vaccination and immune response measured by antibody levels.

Researchers are evaluating the safety, effectiveness, and antiviral activity of CP-COV03 in adults with dengue infection in this randomized, double-blind, placebo-controlled Phase 2/3 clinical trial. The study aims to better understand how well CP-COV03 works compared to a placebo in treating dengue and dengue-like illnesses. In Phase 2, about 210 patients diagnosed with NS1-positive dengue within 72 hours of fever onset will be randomly assigned to receive either placebo or CP-COV03 at doses of 450 mg, 900 mg, or 1,350 mg per day for seven days. An independent Data and Safety Monitoring Board will analyze results to decide the best dose for Phase 3. Participants in Phase 3 include those with dengue and dengue-like illnesses such as zika, influenza, or COVID-19. During the study, researchers will monitor adverse events and serious adverse events from day 1 to day 29. They will measure dengue viral load at several time points up to day 15 and track symptom improvement. Additional tests will assess the drug's behavior in the body, including how much is absorbed and how long it stays in the bloodstream. Participants can expect regular visits for evaluations, monitoring, and safety follow-up during the trial period, which starts in April 2026 and continues until May 2027.

Dengue fever is a viral infection that can affect adults and elderly people, especially in areas where dengue is common. Researchers are studying the Dengue Tetravalent Vaccine (TDV) in adults aged 45 to 60 years and elderly adults aged over 60 to 79 years. The study aims to understand the side effects of TDV and how well it triggers an immune response, including in those with other health conditions like diabetes, high blood pressure, or kidney disease. Participants will receive two injections of TDV or a placebo during the study, with the second dose given three months after the first. Adults aged 45 to 60 years will receive TDV openly, while elderly participants over 60 will be randomly assigned to receive either TDV or a placebo. Injections are given under the skin, and the study is conducted in multiple centers. Throughout the study, participants will visit the clinic five times for monitoring. Researchers will check for local and systemic side effects shortly after each vaccination, assess antibody levels against the dengue virus, and monitor for any serious health events. The study will continue for up to nine months to observe safety and immune responses in all participants.

Researchers are studying the effects of EYU688, an oral medication, compared with a placebo in patients with dengue fever. The study aims to understand how EYU688 affects dengue viral load, fever clearance time, and clinical signs and symptoms. This randomized, participant- and investigator-blinded, placebo-controlled trial includes two parallel groups with different pharmacokinetic sampling schedules. Participants will receive either EYU688 or a matching placebo capsule orally. The study consists of two cohorts running at the same time with intensive pharmacokinetic sampling in one and sparse sampling in the other. The research evaluates safety, efficacy, and pharmacokinetic properties of EYU688 over a treatment period. During the study, participants will undergo assessments including viral load measurement, fever monitoring, laboratory tests for blood counts and liver enzymes, and evaluation of dengue severity signs. Safety will be monitored through adverse event tracking up to 35 days. The primary outcome focuses on viral load reduction 48 hours after treatment starts, with secondary outcomes covering fever duration, clinical recovery, and other health indicators up to 15 days post-fever onset.

Researchers are evaluating the antiviral effects of several experimental drugs in patients with early dengue infection, defined as those with confirmed dengue and less than 48 hours of fever. This adaptive platform trial aims to determine how well these drugs work against the dengue virus and assess their safety and tolerability. The study also explores how these drugs affect various physiological and clinical markers in dengue patients. Participants are randomly assigned to one of four groups: standard care with no study drug, molnupiravir taken orally twice daily for five days, a single intravenous dose of a dengue monoclonal antibody called VIS513, or remdesivir dosed according to weight over five days. The trial is open-label and adaptive, allowing for the addition of new treatments or removal of less effective ones based on ongoing results. During the trial, participants will be monitored from randomization through day 5 for viral clearance and safety, with further follow-up visits at 30 and 60 days after enrollment. Researchers will assess virus levels, fever duration, clinical progression, and laboratory measures such as platelet count and liver enzymes. Safety events and adverse effects are also tracked up to 30 days post-enrollment to ensure participant well-being throughout the study.

Researchers are conducting an international observational study to better understand acute infections in adults who are hospitalized. This study focuses on collecting data and biospecimens to characterize various infectious diseases, including respiratory infections, infections outside the respiratory tract, established infectious diseases, and newly emerging infections. The aim is to gather information that will help identify risk factors, clinical features, and management strategies, as well as to aid in designing future clinical trials. Participants include adults admitted to the hospital with suspected or confirmed acute infections. There is no intervention or treatment being tested, as this is an observational study. The research involves monitoring patients during their hospital stay to collect vital data and samples related to their infection. Participants will be observed over time, with researchers assessing outcomes such as mortality by day 28, time to recovery, clinical improvement by day 7, organ support-free days, and organ failure scores. Data collection includes clinical assessments and biospecimen sampling to better understand infection progression and patient recovery. The study begins in August 2025 and continues through June 2027, allowing for extensive data gathering and analysis.