Active clinical trials for "Malaria"

This study aims to compare the efficacy of monthly IPTp-DP with monthly IPTp-SP to determine if IPTp-DP is associated with a reduction in malaria infection at delivery among HIV-negative women in an area with high levels of SP resistance in Malawi.

Targeted malaria elimination (TME), which comprises appropriate case management by village health workers, vector control and mass drug administration, is currently being implemented through pilot projects in selected villages in the Greater Mekong Subregion (GMS) and the scale-up of the intervention to the regional level are underway. Based on mathematical modelling, extending the post-TME parasitaemia-free period in the majority of villagers for as short as 200 days will substantially increase the chances of achieving the interruption of malaria transmission. Immunogenicity of RTS,S is greater in older children, and the short term malaria protective effect is stronger than the overall effect assessed over 1-2 years. Addition of mass RTS,S/AS01E vaccination to the TME arsenal could provide this much needed additional protection. Currently there are no safety and immunogenicity data for the use of RTS,S/AS01 in Asian populations. This trial will generate the required data for the use of this vaccine in Asian populations. For integration with the current TME activities, which provide mass drug administrations at months M0, M1, and M2, it would be most efficient and practical to provide the vaccine at the same intervals. To address a two round intervention (M0, M2) where a three round intervention is not feasible, one study arm will look at the immune response generated by only two doses of vaccine and antimalarial medications. Recent evidence suggests that a vaccination schedule which includes a fractional dose of RTS,S/AS01 (1/5th of the standard dose) could be similarly or more protective than a schedule with three standard full doses, while requiring less vaccine and resources. The trial therefore includes study arms which will assess the safety and immunogenicity of fractional dose schedules. Each participant will be randomized into one of the following study arms in a ratio of 20:20:30:30:30:30:30, as follows: RTS,S/AS01B Fractional dose group (Group 1) Double RTS,S /AS01E Fractional dose group (Group 2) RTS,S/AS01E Standard dose group (Group 3) RTS,S/AS01E + DHA-PIP+PQ Standard dose group (Group 4) RTS,S/AS01E Fractional dose group (Group 5) RTS,S/AS01E + DHA-PIP+PQ Fractional dose group (Group 6) RTS,S/AS01E + DHA-PIP+PQ Fractional two-dose group (Group 7)

In the underlying study, a genetically modified P. berghei parasite is used. P. berghei is one of the four Plasmodium species that causes malaria in rodents. The hypothesis is that immunization of humans with P. berghei will induce a cross-species immune response without the risk of a breakthrough infection. To further increase the potential for protective efficacy, the P. falciparum circumsporozoite (CS)- protein gene has been integrated in the P. berghei parasite, generating a genetically modified P. berghei parasite, abbreviated as Pb(PfCS@UIS4).

A double-blind, individual randomised trial will be undertaken in 6000 children under the age of five years living in areas of Burkina Faso or Mali where the transmission of malaria is intense and highly seasonal to determine whether the malaria vaccine RTS,S/AS01 is (a) as effective as SMC with SP + AQ in preventing clinical malaria (b) provides additional, useful protection when given together with SMC. The primary trial end-point will be the incidence of clinical episodes of malaria detected by passive case detection.

This will be a single-arm observational cohort study. Malaria patients with Plasmodium vivax and meeting study inclusion criteria, who give consent to be enrolled in the study, will have their G6PD status measured by the CareStart™ G6DP rapid diagnostic test (G6PD RDT), and primaquine prescribed according to the result. According to the G6PD RDT result, primaquine will be prescribed at 0.25mg/kg/day for 14 days (normal patients) or 0.75mg/kg weekly for eight weeks (deficient patients). All will receive treatment with chloroquine to clear asexual stages of infection. Patients will be reviewed at day 2, day 7 and day 14. At these visits patients will undergo a brief clinical assessment and a small blood sample will be taken for repeat haemoglobin measurement and dried blood spot for carboxyprimaquine measurement (day 7 and day 14 only). In general, antimalarial treatment will be unsupervised to reflect field conditions. However a subset of 25 G6PD normal patients at a single site will have each day of their primaquine treatment administered and observed at the treatment centre. This is to determine a calibration curve for primaquine pharmacokinetic studies. Dried blood spots will be stored appropriately. Day zero samples will be genotyped in Bangkok (MORU, Dr. Mallika Imwong) after DNA extraction. PCR-RFLP will be used to detect the allele associated with the Mediterranean variant of G6PD deficiency. In addition DNA extracts will be sent for more systematic genetic testing for known G6PD variants through existing collaborations with the Wellcome Trust Sanger Institute. The day 7 and 14 dried blood spot samples will be analysed in the MORU pharmacology laboratory for primaquine and carboxyprimaquine concentrations, from which adherence to primaquine can be determined retrospectively, using the subset of 25 patients receiving directly observed therapy to calibrate the results. Funder: WellcomeTrust, Grant reference: 107548/Z/15/Z

Single center, randomized, placebo-controlled, double-blinded trial using PfSPZ Challenge (NF54) under A/P chemoprophylaxis for immunization and PfSPZ Challenge (NF54) and PfSPZ Challenge (7G8) for repeat CHMI. A total of 30 adult, healthy, malaria naïve volunteers will receive three injections by Direct Venous Inoculation (DVI) of either placebo (n = 10), 51,200 PfSPZ Challenge (NF54) (n = 10), or 150,000 PfSPZ Challenge (NF54) (n = 10) under chemoprophylaxis with A/P at 4 week intervals. The placebo will be normal saline (0.9% NaCl). Ten weeks after the last dose of PfSPZ Challenge (NF54) for immunization, volunteers will undergo first CHMI and followed until asexual blood stage parasitemia, detected by quantitative real time PCR (qPCR) or thick blood smear microscopy. If parasitemic, they will be treated with A/P (used in this case as a standard treatment regimen). In the event of no parasitemia, volunteers will be followed until Day 28 post-CHMI and will not receive A/P. Sixteen to forty-four weeks after the last immunization, a second CHMI will be administered to assess longevity and cross-strain protection. All volunteers will be followed up to 28 days post-inoculation. Those developing parasitemia will be treated with A/P. Volunteers of Group A will have CHMI with PfSPZ Challenge (NF54) followed by PfSPZ Challenge (7G8). Volunteers of Group B will have CHMI with PfSPZ Challenge (NF54) or PfSPZ Challenge (7G8) followed by PfSPZ Challenge (7G8). In the case that protective efficacy in Group A is ≥75% CHMI sequence will be 7G8-7G8. In the case that protective efficacy against homologous Challenge in Group A is <75%, volunteers will receive the same sequence as in Group A (NF54-7G8).

This phase I trial of the replication-intact PfSPZ Challenge vaccine given under CQ cover will enroll 28 healthy volunteers to receive PfSPZ or placebo, as well as suppressive doses of chloroquine (CQ)on varying schedules. 10 weeks post 3rd immunization subjects will be subjected to controlled human malarial infection. The primary objective of this study is to evaluate the safety and tolerability of escalating doses of Sanaria PfSPZ Challenge administered by DVI on varying schedules to healthy malaria-naïve adults taking suppressive doses of CQ (PfSPZ-CVac).

This Phase 1 study will be conducted to explore the dose regimen in humans and to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and toxicological effects of meplazumab in healthy subjects, thus providing a new macromolecule antibody drug for the prevention and treatment of P. falciparum infection.

This community-based cluster randomized controlled trial aims to evaluate the effectiveness of time-limited, community-wide mass drug administration (MDA) with dihydroartemisinin-piperaquine (DHA-PPQ) and single low-dose primaquine (SLD-PQ) on Plasmodium falciparum transmission compared to standard-of-care seasonal malaria chemoprevention (SMC). The study will be conducted in a moderate-to-low malaria transmission setting of Senegal with optimized malaria control measures (e.g., proactive community case management and piperonyl butoxide pyrethroid long-lasting insecticidal nets (PBO LLINS)).

This is a randomized, double blind, placebo-controlled, single site, trial of a condensed regimen of PfSPZ Vaccine administered on Days 1, 8 and 29 by direct venous inoculation (DVI) to assess safety, tolerability, immunogenicity and vaccine efficacy (VE) against heterologous controlled human malaria infection (CHMI) conducted at varying time intervals after the third immunization (14, 42 or 70 days). The trial is designed to simulate pre-deployment immunization of military personnel. Prior studies with this regimen show high level protection (>80%) against CHMI at 21 days, but the onset and duration of protection have not been fully defined.