Malaria Falciparum

This study aims to evaluate whether GSK3772701 alters the pharmacokinetics (PK) of midazolam (MDZ), a standard probe substrate for the CYP3A4 enzyme. The findings are planned to be used to determine whether GSK3772701 acts as an inducer and/or inhibitor of CYP3A4 and will help guide recommendations for safe co-administration with CYP3A4 substrates.

This is a randomized, double-blind, placebo-controlled Phase 1 trial of Plasmodium falciparum (Pf) sporozoite (SPZ) late-arresting replication-competent (LARC) malaria vaccine (PfSPZ-LARC2 Vaccine) administered to healthy, malaria-naive study participants in Germany by direct venous inoculation (DVI) to determine safety, tolerability, and vaccine efficacy (VE) against controlled human malaria infection (CHMI). PfSPZ-LARC2 Vaccine contains a deletion of two genes, the Mei2 and LINUP genes, and undergoes developmental arrest in the late liver stages without releasing merozoites into the blood stream (blood stage parasites). The primary objective of the study is to assess the safety and tolerability of administration of PfSPZ-LARC2 Vaccine, with special attention to the adequacy of attenuation, in the intention-to-treat (ITT) population.

This is a single-centre, participant- and investigator-blind, randomised, placebo controlled, single ascending dose study to assess the safety, tolerability and PK of a single dose of IM depot injection(s) of LAI formulations of MMV055 administered alone (Part A) and in combination with MMV371 (Part B) in healthy participants. It is planned to enroll up to 6 sequential cohorts of 8 healthy male participants and healthy female participants of non-childbearing potential in Part A. In Part B, up to 3 sequential cohorts of 8 healthy male participants and healthy non-pregnant, non-lactating female participants will be enrolled. In each cohort, participants will be randomised in a ratio of 6 active investigational medicinal product (IMP) to 2 placebo. Part A of the study will include two components, Parts A1 and A2. Part A1 includes two initial cohorts, with planned doses of 40 and 100mg, respectively. It is intended to document the human elimination T1/2 of MMV055, which will then be used to shorten the proposed End of Study (EOS) of 48 weeks, if possible. All cohorts will follow a sentinel dosing design. On Day 1, two sentinel participants (sentinel group) will be randomly assigned to receive a single IM dose of either active IMP or placebo (1 participant each) to assess safety and tolerability (including ISRs). The sentinel group will be dosed concomitantly at least 7 days prior to the rest of the cohort (main group). The main group will comprise 6 participants randomly assigned to receive a single IM dose of either active IMP or placebo in a 5:1 ratio to assess safety and tolerability (including ISRs).

This study will assess the safety, tolerability, and pharmacokinetic properties of GSK4425689A monoclonal antibody (mAb) in healthy adults, when administered by either intravenous (IV) or subcutaneous (SC) routes.

This Phase 1b study will assess the safety, tolerability and pharmacokinetics (PK, this measures the levels of study drug in the body) of a single injection of MMV371 in healthy adult and adolescent participants in Rwanda. MMV371 has been designed as a long acting injection (LAI). Protective efficacy (PE) will be assessed as an exploratory endpoint. Protective efficacy measures if participants are protected from becoming ill with malaria whilst the MMV371 is still present in their body. The study will enroll approximately 80 healthy male and female participants, aged 12 to 50 years. Before starting the study participants will be given a standard approved course of artemether lumifantrine (AL) to clear any malaria infection they have. Once the AL course has been completed the study drug will be given by injection in the muscle of the upper arm, the side of the thigh, or the hip. Three out of four participants will receive MMV371 and 1 in four participants will receive placebo. Placebo is a dummy medicine. All participants have an equal chance of being assigned to receive the injection in the upper arm, outer thigh or hip. Neither the participants nor the researchers treating the participants will know who received MMV371 or placebo until after the study is completed. Key study features include: * Study duration for each participant: up to 7 months * MMV371 or placebo given: a single intramuscular (IM) injection * Visit schedule: Participants will remain in-clinic on Days -1-2 (2 overnight stays), followed by 15 follow-up visits: Day 4, then weekly for 1 month, and subsequently every 2 weeks until the End-of-Study (EoS) visit at Week 24. These frequent visits are necessary to monitor safety, the levels of MMV371 in the body, and to perform malaria detection testing until EoS (Week 24).

The study will evaluate the safety and efficacy of a new antimalarial drug GSK3772701 (a pyrrolidinamide), using different doses and treatment durations, in adult participants with uncomplicated Plasmodium (P.) falciparum malaria.

The primary purpose of the study is to characterise the safety of GSK4024484 in healthy participants within a controlled pharmacokinetic (PK) range, and the effect of food on the study intervention.

The resilience of P. vivax to malaria elimination efforts is due to its ability to form dormant liver stages (hypnozoites) that reactivate weeks to months after the initial infection causing recurrent episodes of malaria (relapses) and ongoing parasite transmission. Relapses account for a majority of recurrent infections and clinical cases of P. vivax malaria, and therefore have a significant effect on morbidity at the individual level. With current technology, it is not possible to directly measure hypnozoite biomarkers. Rather than directly detecting hypnozoites, our team developed an indirect approach by measuring antibodies induced by the primary blood-stage infection. Antibodies to different blood-stage antigens decay at different rates. Measuring antibodies to a carefully selected panel of P. vivax antigens can aid to identify individuals who have been infected within the previous 9 months (approximately the lifespan of hypnozoites). A serological test based on selected P. vivax antigens can detect recent exposure and predict future relapses. Coupling this test with a safe and efficacious primaquine treatment regimen, results in a population-based intervention to target the hypnozoite reservoir. This intervention is referred to as Plasmodium vivax Serological Testing and Treatment (PvSeroTAT). PvSTATEM is a cluster randomised trial in Madagascar and Ethiopia. This study will provide insights into the feasibility, acceptability, and efficacy of the PvSeroTAT approach. In this study, individuals, randomised by clusters, will be tested for the presence of serological markers of a recent P. vivax infection, followed by a targeted drug treatment intervention aimed at killing P. vivax hypnozoites.

Previous malaria control studies in Ghana have shown that community-wide approaches can substantially reduce malaria infections. In a mass testing, treatment and tracking (MTTT) study, more than 75% of people in target communities were reached, leading to a 24% reduction in asymptomatic malaria after one year. However, rapid diagnostic tests (RDTs) can miss very low-level infections, meaning some infected individuals are not treated and can continue to spread malaria. A pilot malaria mass drug administration (MDA) study using artemether-lumefantrine (AL) in the Eastern Region of Ghana showed a very large reduction (over 95%) in parasite carriage after repeated rounds of treatment. Despite this success, malaria infections later fluctuated, possibly because some parasites remained in mosquitoes and because mature gametocytes-the parasite stage responsible for transmission-are not fully eliminated by standard malaria medicines. To better interrupt malaria transmission, this study will use MDA with dihydroartemisinin-piperaquine (DHAP) combined with a single low dose of primaquine (PQ), which targets these transmission stages. The intervention will be given to the whole community every two months (six times per year) and compared with the current standard malaria control measures. The study will examine whether this approach reduces malaria parasite carriage, whether malaria returns after treatment stops, and whether repeated MDA affects malaria drug resistance markers in the population. This two-year implementation research will generate practical evidence to guide national malaria policy in Ghana and inform the potential use of MDA in other malaria-endemic African countries.

Malaria remains a major cause of pediatric deaths and morbidity in Africa. An affordable malaria vaccine, R21, is being deployed in Uganda and other African countries with high malaria transmission, but efficacy is incomplete and wanes rapidly, and R21 does not provide protection until infants complete the primary vaccination series, or \~9 months of age. The goal of this study is to see whether combining R21 vaccination with two novel perennial malaria chemoprevention regimens can enhance protection against malaria compared with R21 alone. This study will take place at Masafu General Hospital (MGH) in Busia District, a rural area in Southeastern Uganda bordering Lake Victoria.

The goal of this clinical trial is to learn if the genetically-modified malaria parasite NF54/iGP3 will safely infect humans with malaria. The investigators will also determine how the parasite grows in humans, and the effect of anti-malarial drugs. Researchers will use a controlled human malaria infection (CHMI) model to infect participants with malaria to observe the development of the disease, collect malaria-infected blood, and then treat the participants to cure the malaria infection. The collected malaria-infected blood will be used to create a frozen stock of malaria parasites for use in future research.