Malaria

Researchers are evaluating the safety and feasibility of a controlled human Plasmodium vivax malaria infection (CHMI) in healthy adult Thai volunteers. This study aims to find the best dose of cryopreserved P. vivax infected red blood cells for future studies by experimentally injecting these infected cells into volunteers. The study involves up to 48 participants, who will be closely monitored in a hospital setting, with the goal of understanding the infection process and treatment responses. Participants will receive one of four doses of infected red blood cells, ranging from a whole vial to diluted amounts, administered by injection. Each dose will be tested in groups of volunteers to identify which dose reliably produces infection. The study includes a screening period, a challenge day for infection, a monitoring phase until treatment criteria are met, and a follow-up period lasting one year after treatment. Volunteers will be admitted to the hospital for close monitoring, including daily health checks and blood tests to detect malaria parasites and assess immune responses. After infection is confirmed, blood samples will be taken twice daily until participants meet treatment criteria, at which point antimalarial drugs will be given. Follow-up visits will occur over the next year to monitor health, immune response, and possible parasite transmission. Safety and infection outcomes will be analyzed throughout the study period.

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 evaluating a revised weight-based dose of tafenoquine (target dose 7.5mg/kg) to treat patients with vivax malaria. This Phase 3 trial aims to determine if this revised regimen is not worse than a high dose of primaquine given over seven days and if it is better than the standard fixed dose of tafenoquine. The study also looks at how well patients tolerate the revised dose and whether it is practical to use. Participants will be randomly assigned to one of three groups. One group will receive a single weight-based oral dose of tafenoquine along with schizontocidal treatment. Another group will receive a single fixed oral dose of 300mg tafenoquine plus schizontocidal treatment. The third group will receive schizontocidal treatment plus a high dose of primaquine given orally over seven days. The trial will monitor safety and effectiveness over several months. During the study, participants will be followed for six months. Researchers will assess the occurrence of vivax parasitaemia at 4 and 6 months as the main outcome. Other measurements include symptomatic vivax parasitaemia, anemia incidence at different time points, hemoglobin changes, adverse events, and methemoglobin levels. Participants must provide informed consent and live in the study area to allow regular follow-up and monitoring throughout the trial.

Researchers are evaluating the safety, tolerability, and how the body processes (pharmacokinetics) a new oral drug called E1018 in healthy adult volunteers. This early phase 1 study aims to understand how E1018 behaves in the body after a single dose and to monitor any possible side effects. The study includes adults from 18 to 55 years old who do not smoke or vape and have a healthy body mass index. Participants will receive single ascending doses of oral E1018 or a matching placebo in different groups. The study is randomized and double-blinded, meaning neither the participants nor the researchers know who receives the active drug or placebo to ensure unbiased results. Dosages are given on specified days, and the study includes several cohorts to assess the effects of increasing doses. During the study, participants will be closely monitored through physical exams, vital signs, laboratory tests, electrocardiograms (ECGs), and urine and blood sample collections to measure drug levels and safety markers. The primary outcomes include tracking any adverse events, dose-limiting toxicities, and detailed pharmacokinetic measurements up to 20 days after dosing. Participation involves regular visits for assessments and lasts through the observation period to ensure safety and gather data.

Researchers are evaluating the safety and immune response of a multi-stage malaria vaccine candidate combining R21 with RH5.1 and/or R78C in Matrix-M adjuvant. This Phase Ib open-label study includes healthy adults aged 18 to 35 years and children aged 5 to 17 months in Burkina Faso. The study aims to test different combinations of these vaccines to better understand their effects in populations living in malaria-endemic areas. Participants are divided into six groups. Adults receive three doses of 5 µg R21 plus 10 µg RH5.1 and 10 µg R78C. Children receive different combinations of 5 µg or 10 µg doses of R21, RH5.1, and R78C vaccines. Each participant receives three intramuscular injections at months 0, 1, and 6, either in the deltoid muscle for adults or the anterolateral thigh for children. Safety monitoring includes staggered recruitment, sentinel participants, and Data Safety Monitoring Board reviews before age de-escalation and subsequent vaccinations. Participants will undergo safety assessments for solicited and unsolicited adverse events at multiple time points up to one year following the first vaccination. Blood samples for immunology testing will be collected at screening, vaccination days, and several follow-ups up to day 365. The study includes ongoing monitoring of serious adverse events and immune responses to evaluate how well the vaccine combinations are tolerated and stimulate the immune system over time.

Researchers are studying the safety and immune response of different dosing schedules and reduced doses of the RTS,S/AS01E malaria vaccine in healthy children aged 5 to 60 months living in areas where malaria is common. This Phase 2a open-label randomized study aims to find the best vaccination regimen to protect young children against malaria, a serious infectious disease. The study is sponsored by GlaxoSmithKline and targets healthy children who have completed routine immunizations. Participants are randomly assigned to receive three doses of the RTS,S/AS01E vaccine on one of three schedules: Day 1, Month 1, and Month 2; Day 1, Month 1, and Month 7; or Day 1, Month 2, and Month 7. The vaccine is given as an injection into the muscle. The study follows participants for up to 19 months to compare immune responses and safety across these different dosing schedules. During the study, children will have blood tests at multiple time points to measure antibodies against malaria and hepatitis B, along with monitoring for any side effects following vaccination. Researchers will track any adverse events, including serious ones, for up to 19 months after the first dose. Parents or guardians will complete diaries and attend follow-up visits to help monitor health and vaccine effects throughout the study period.

Malaria, caused by Plasmodium parasites, remains a leading cause of illness and death worldwide, with Plasmodium falciparum responsible for most fatalities, especially in young children. This study aims to evaluate a new combination therapy of ZY19489 and ferroquine (FQ) designed to treat asymptomatic adult carriers of P. falciparum with a shorter dosing regimen. The goal is to assess the safety and tolerability of this combination given as a one- or two-day oral treatment. Participants will be randomly assigned to receive the ZY19489-FQ combination or placebo orally after fasting for at least 10 hours. Three dosing cohorts will be tested: one with 600 mg each of ZY19489 and FQ once daily, another with 900 mg each once daily, and a third cohort receiving 600 mg each daily for two days. The study includes a total of 36 adults divided across the cohorts. Each participant will be involved in screening visits followed by approximately 64 days of follow-up, totaling around 10 weeks in the trial. Researchers will monitor safety by recording any adverse events and evaluate pharmacokinetics, including drug concentration and elimination measures from the time of dosing until study completion. Participants will undergo scheduled visits for assessments, laboratory tests, and adherence monitoring throughout the study period.

Researchers are evaluating the effectiveness, safety, and tolerability of a new fixed-dose triple combination therapy called artemether-lumefantrine-amodiaquine (ALAQ) compared to two existing artemisinin-based combination therapies (ACTs) for treating uncomplicated Plasmodium falciparum malaria. This open-label, randomized, controlled trial aims to determine whether ALAQ works as well and is as safe and tolerable as the current standard two-drug treatments. The study includes participants from Africa and Asia, with some sites incorporating a single low-dose primaquine treatment depending on local policies. Participants will be randomly assigned to one of three treatment groups: ALAQ, artemether-lumefantrine (AL), or artesunate-amodiaquine (ASAQ). Treatments are given under direct observation over three days, with ALAQ and AL administered in six doses spaced between the start time and 60 hours later, while ASAQ is given once daily for three days. Participants stay in an inpatient unit for the first three days to receive treatment and undergo study procedures, followed by weekly visits up to day 42 for monitoring. During the study, researchers will perform daily malaria parasite counts, physical exams, vital sign checks, symptom questionnaires, and laboratory tests including blood counts, liver and kidney function, and heart monitoring with electrocardiograms. Pharmacokinetic studies and parasite genetic testing will also be conducted to understand drug levels and resistance patterns. Safety, efficacy at 28 and 42 days, and treatment tolerability will be closely tracked. Participants may visit the clinic between scheduled visits if they experience any symptoms. The total participation lasts up to 42 days from treatment start.

Researchers are evaluating the safety and pharmacokinetics of GSK4024484, a drug given orally, in healthy adult volunteers aged 18 to 60 years. This phase 1 study aims to understand how the drug behaves in the body within controlled dose ranges and to assess the effect of food on the drug's absorption and action. The study includes both single and multiple doses of GSK4024484 as well as placebo comparisons to monitor safety and reactions. Participants receive various single oral doses of GSK4024484 ranging from 6 mg up to 400 mg, all administered with 240 mL of water in a fasting state, with one group receiving a dose in a fed state to test food effects. There are also groups receiving multiple ascending doses over three days (150 mg or 300 mg per day) and corresponding placebo groups. Some optional dose groups allow adjustments if dose escalation needs modification or repetition. During the study, participants undergo medical evaluations including physical exams, laboratory tests, cardiac assessments, and monitoring for adverse events. Researchers track serious and non-serious side effects from the time of informed consent through follow-up days extending up to around 38 to 40 days post-dose. Pharmacokinetic measures such as drug concentration in blood over time and half-life are also recorded to understand how the drug is processed. The total participation time covers initial dosing through follow-up contacts to ensure safety and gather data.