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NCT06652737
This is a first-in-humans randomized, double-blind, placebo-controlled, age de-escalation Phase 1 trial of Plasmodium falciparum (Pf) late liver stage-arresting replication-competent (LARC) sporozoite (SPZ) malaria vaccine (Sanaria® PfSPZ-LARC2 Vaccine) administered to healthy, malaria-exposed adults and children by direct venous inoculation (DVI) to determine safety, tolerability, and immunogenicity. The PfSPZ comprising PfSPZ-LARC2 Vaccine contain a double gene deletion, of the Mei2 and LINUP genes. As a result, they undergo developmental arrest in the late liver stages without releasing merozoites into the blood stream (no blood stage parasites are produced, either asexual or sexual). Because Pf parasites with the LARC phenotype replicate in the liver before disintegrating, they amplify and diversify parasite protein expression and are expected to be a potent immunogen to induce anti-malarial immunity, equaling or exceeding the potency and efficacy of the replication-competent chemo-attenuated Sanaria® PfSPZ-CVac (chloroquine). Because the parasites are intrinsically attenuated, they are also expected to be safe and well tolerated, similar to radiation-attenuated Sanaria® PfSPZ Vaccine and to the single-gene(Mei2)-deleted GA2 parasites (also LARC phenotype) tested at the Leiden University Medical Center (LUMC), which, like PfSPZ-LARC2 Vaccine, disintegrate after replicating in the liver. PfSPZ-LARC2 Vaccine thus avoids the safety concerns associated with PfSPZ-CVac, which uses fully infectious, non-attenuated parasites to achieve replication and depends on co-administered chloroquine for attenuation. In summary, the genetically attenuated PfSPZ-LARC2 Vaccine should combine the best-in-class immunogenic potency and protective efficacy of PfSPZ-CVac (chloroquine) with the excellent safety and tolerability of intrinsically attenuated PfSPZ Vaccine and GA2 vaccine. This trial is designed to test the hypotheses that: 1. The vaccine is safe and well tolerated in each age group. 2. The true rate of breakthrough blood stage infection (or other concerning adverse events) is less than about 5%, with an 95% confidence level (this will be the level of confidence that there are no breakthroughs if no breakthroughs occur in the 50 participants receiving PfSPZ-LARC2 Vaccine).
NCT07362498
This implementation study evaluated the health systems feasibility, economic costs, and stakeholder acceptability of deploying multiple first-line therapies (MFTs) that were of the artemisinin-based combination therapies (ACTs) type, for uncomplicated malaria in Western Kenya. The study included a nested observational molecular surveillance of antimalarial resistance markers in Plasmodium falciparum parasites. The implementation program involved adaptive cycling of four ACTs across 28 health facilities over 28 months (June 2020 - October 2022) with and extension to January 2024 in one geographic area (Mfangano Island). Health systems outcomes (feasibility, costs, acceptability) are reported in Cole et al., Malaria Journal 2024. Molecular surveillance outcomes (resistance marker prevalence and temporal trends) are reported in a companion manuscript currently under peer-review.