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).
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Assess safety, namely adequacy of attenuation, of PfSPZ-LARC2 Vaccine by measuring number of trial participants with presence of breakthrough blood stage infection
Timeframe: First 28 days after immunization with PfSPZ-LARC2 Vaccine
Assess the safety of PfSPZ-LARC2 administration by measuring incidence of related grade 3 solicited and unsolicited adverse events (AEs) in the 28 days after PfSPZ-LARC2 Vaccine administration
Timeframe: First 28 days after immunization with PfSPZ-LARC2 Vaccine
Assess the safety of PfSPZ-LARC2 administration by measuring incidence of related grade 3 abnormal laboratory values one week after PfSPZ-LARC2 Vaccine administration
Timeframe: 7 days after immunization with PfSPZ-LARC2 Vaccine
Assess the safety of PfSPZ-LARC2 administration by measuring incidence of related serious adverse events (SAEs) throughout the study period
Timeframe: Entire study period (approximately 6 months)