Active clinical trials for "Malaria"

This study aims to evaluate the safety and efficacy of a standard chloroquine drug regimen administration supplemented with dehydroepiandrosterone sulfate against drug-resistant malaria.

Malaria is still responsible for more than 627,000 deaths each year, predominantly among children under 5 years old. Current reductions in deaths have stagnated, and additional setbacks for malaria control programs due to the Coronavirus Disease 2019 (COVID-19) pandemic are expected. To achieve malaria elimination and eradication a leverage concerted approaches to reduce clinical disease and prevent new infections is a must. The existing malaria controls tools including the a recombinant protein-based malaria vaccine (RTS,S ,(trade name MosquirixMosquirix )), a malaria vaccine currently undergoing implementation studies and endorsed by the World Health Organization on October 7, 2021, can reduce disease burden for patients but cannot ultimately support malaria elimination and eradication since their effect on malaria transmission is at most partial. Consequently, complementary interventions, such as transmission-blocking vaccines (TBVs) may prove to be a cost-effective intervention that can reduce on-going residual transmission and the cascade of new infections.

Background: Mortality from severe malaria remains ~15% despite the use of the most rapidly parasiticidal antimalarial therapy, artesunate. Adjunctive treatments may improve outcome. Our overall goal is to determine if adjunctive treatment with L-arginine is safe and improves outcomes in severe malaria. In studies to date, we have shown that L-arginine is safe in moderately severe malaria, increases nitric oxide production and improves endothelial function. We now propose to extend these studies to patients with severe malaria. Aims: To determine the safety, preliminary efficacy, pharmacokinetics and pharmacodynamics of L-arginine infusion in severe malaria. Hypothesis: L-arginine will improve endothelial function, lactate clearance time and tissue oxygen delivery compared to saline with no clinically significant adverse effects. Methods: Based on previous pharmacokinetic modeling and simulations, we propose a phase 2A randomised controlled trial of L-arginine vs saline in severe malaria, each given over 8 hours. If safety is demonstrated this will be followed by a phase 2B open-label study of 24-hour infusion of L-arginine in severe malaria with safety and preliminary efficacy compared with the 8 hour infusions given in phase 2A. The primary outcomes will be the improvement in endothelial function and lactate clearance in patients given L-arginine infusion compared with those who received saline. Among the secondary outcomes will be safety and the effect of L-arginine vs saline on tissue oxygen delivery (NIRS). Data from both phase 2A and 2B will be used to generate a pharmacokinetic/ pharmacodynamic model.

This is a randomized, dose-escalation Phase I/IIa trial with controlled human malaria infection to evaluate safety, tolerability, immunogenicity (Part A) and efficacy (Part B) of an investigational RNA-based vaccine (BNT165e) for prevention of P. falciparum malaria in healthy malaria-naive adults. The multi-antigen malaria vaccine (designated BNT165e) is a combination of three distinct RNAs, BNT165c and BNT165d (composed of BNT165d1 and BNT165d2), encoding P. falciparum antigens encapsulated in lipid nanoparticles (LNPs). The BNT165c RNA encodes the Plasmodium falciparum circumsporozoite protein (PfCSP). The BNT165d1 and BNT165d2 RNAs both encode conserved, immunogenic segments of liver stage-expressed proteins.

Controlling malaria during pregnancy is a vital strategy in decreasing maternal and child mortality in Africa. There are data from clinical trials and program evaluations in stable transmission areas that show that intermittent preventive treatment (IPT) with two doses of sulfadoxine-pyrimethamine (SP) is safe, efficacious, and effective in preventing maternal anemia, placental parasitemia, and low birth weight (LBW). SP is also the first-line drug for the case-management of malaria in pregnancy. Resistance to SP, however, is increasing rapidly in East and Central Africa and compliance to the rescue treatment, 7-days of oral quinine, is low. There is an urgent need to find effective, safe and practical alternative drugs for the treatment of malaria in pregnancy. The synergistic antifolate combination chlorproguanil-dapsone (CD), has recently become available. It is inexpensive, well tolerated, is given as single daily treatment doses for 3 days, and is effective in the treatment of drug-resistant falciparum malaria. The investigators propose a small pharmacokinetic study of CD to determine if current fixed combination CD tablets provide an adequate dosage in pregnancy. Such a study is a necessary precursor to any large Phase II trials to further evaluate the safety and efficacy of CD for use in pregnant women. To accomplish this, a group of 66 parasitemic pregnant women in this open label trial will receive CD and be sampled by venipuncture at two of the seven follow-up visits scheduled for pharmacokinetic analyses, such that 11 patients are sampled at each of 12 time points. To serve as a reference, 66 non-pregnant women with symptomatic malaria will also be treated with CD and will have identical pharmacokinetic (PK) analyses performed. Pregnant women greater than or equal to 20 weeks gestation with P. falciparum parasitemia on peripheral blood film will be given an insecticide-treated net (ITN) and will receive CD (1.5 or 2 tablets daily for 3 days, depending on weight). All study drug dosing will be observed. Women will be examined, adverse events recorded, and blood samples collected at days 0, 1, 2, 3, 7, 14, 21, and 28 after treatment, and thereafter every 14 days until delivery. Women will be further randomized to receive additional blood draws for pharmacokinetic analyses using a modified rich PK schedule. Each woman will only have 2 additional blood draws. Women at delivery will have peripheral and placental blood films prepared. Newborns will be weighed, examined, and gestational age determined. Women requiring antimalarial treatment for parasitemia at any point between enrollment and delivery will be treated with quinine. Adverse effects will be assessed at each scheduled visit, any sick visits during the study, and at delivery.

This will be a double-blind, individually randomised trial, to assess the safety, tolerability, immunogenicity, and protective efficacy of two and three doses of the R21/Matrix-M1 malaria vaccine or placebo given at 4 week intervals in healthy women of childbearing potential (WOCBP), who are on pregnancy prevention during vaccination, but report plans to become pregnant in the near future. Participants will be randomised in Year 1 into three groups in a 1:1:1 ratio: Arm 1 (n=110): will receive three doses of R21/Matrix-M1 malaria vaccine at months 0, 1 and 2. Arm 2 (n=110): will receive normal saline (placebo) at month 0 and two doses of R21/Matrix-M1 malaria vaccine at months 1 and 2. Arm 3 (n=110): will receive three of doses normal saline (placebo) at months 0, 1 and 2. In Year 2: Non-pregnant participants in arms 1 and 2 will be randomised in a 1:1 ratio to receive a booster dose of R21/Matrix-M1 malaria vaccine or placebo at the beginning of the malaria transmission season. Participants in the control group (arm 3) will receive normal saline (placebo). Initial follow-up will be for two years after dose three, with an efficacy analysis at 6, 12, 18 and 24 months after dose 3. Participants will be monitored for safety, tolerability, immunogenicity, and malaria infection during the follow-up period. Participants will also be monitored for pregnancy over 12 months post primary and booster vaccination and those who become pregnant will be followed during their pregnancy and for 1 year post-delivery (as well as their offspring) for safety and malaria infection

This stepped-wedge cluster-randomized controlled trial with nested mixed methods study will assess the effectiveness, acceptability, feasibility and cost-effectiveness of a personal protection package to reduce malaria transmission among mobile and migrant populations (MMPs) and the general population in their residing villages in Lao People's Democratic Republic (PDR) and Cambodia.

This will be an open label cluster randomized study with two active intervention and one control arm. A cluster will be defined as a selected village. One district implementing seasonal malaria chemoprevention (SMC) will be selected, and six villages will be randomly selected in this district. These six villages will be randomly allocated to each of the three study arms; 1) Arm 1 will receive IPTsc with sulphadoxine-pyrimethamine plus amodiaquine (SPAQ); and 2) Arm 2 will receive dihydroartemisinin-piperaquine (DP) plus Ivermectin (IVM), all given monthly during the transmission season and 3) Control Arm which will have standard malaria control measures including case management and vector control measures as applicable.

This project is the third part of a 5-year research program entitled "Malaria Infection Studies in Thailand (MIST)" and known as MIST3. MIST3's primary objectives are to assess the safety of the PvRII/Matrix-M vaccine candidate in healthy adult Thai volunteers and to establish whether the PvRII/Matrix-M vaccine can demonstrate a reduced parasite multiplication rate in vaccinated volunteers compared to a controlled group (placebo vaccine) in a blood-stage controlled human malaria infection model. This study will recruit up to 36 eligible healthy volunteers aged 20-55 in Thailand at the Faculty of Tropical Medicine, Mahidol University. Eighteen volunteers will receive three doses of the PvRII/Matrix-M candidate vaccine, and 18 volunteers will receive three doses of the placebo vaccine. Safety and immunogenicity will be evaluated after each dose as per protocol. Approximately four weeks after receiving the third vaccination, 24 volunteers will undergo blood-stage CHMI with Plasmodium vivax. The volunteers will be monitored closely as in-patients in the Hospital for Tropical Diseases and treated according to the Research Proposal Submission Form. This study is funded by the UK Wellcome Trust. The grant reference number are Oxford/MORU: 212336/Z/18/Z and 212336/Z/18/A, and Mahidol University: 212336/A/18/Z and 212336/A/18/A

This is a two-arm, open label Treatment Study comparing the efficacy, safety, tolerability and pharmacokinetics of a three-day course of Dihydroartemisinin-Piperaquine (DP) with or without single-dose primaquine in patients with uncomplicated Plasmodium falciparum malaria. On the last day of DP therapy, volunteers will be randomized to receive either a single 45 mg dose of primaquine (PQ) or DP treatment only (no primaquine).