Planning for Na-GST-1 Hookworm Vaccine Phase 2 CHIM Efficacy Trial

Project Summary/Abstract This R34 grant proposal is to plan a clinical trial that will test the proof-of-concept that the lead candidate hookworm vaccine antigen, Na-GST-1, can have a meaningful biological impact on hookworm infection. This trial will utilize an innovative paradigm for early assessment of investigational vaccine antigens by challenging human volunteers using a controlled human infection model (CHIM) after vaccination. Hookworm is one of the most important parasitic infections, with over 400 million people infected worldwide, most with the Necator americanus species. The clinical hallmark of hookworm infection is iron deficiency anemia resulting from intestinal blood loss. Na-GST-1 is a critical component of the blood-feeding pathway of N. americanus and was selected for clinical development based on its protective efficacy in animal trials. Recombinant Na-GST-1, formulated on Alhydrogel, has been shown to be safe when administered to healthy adults and children in Phase 1 trials. In a small pilot Phase 2a CHIM proof-of-concept study conducted in hookworm-naïve volunteers, Na-GST-1/Alhydrogel administered in combination with the CpG 10104 immunostimulant, provided significant protection against a single challenge with NaL3 larvae. In the proposed study, healthy hookworm‐naïve adult volunteers will be vaccinated with Na-GST-1/Alhydrogel/CpG 10104 according to different doses followed by challenging them with repeated doses of infective N. americanus larvae to assess the effect of vaccination on infection, as assessed by parasitologic, immunologic and hematologic parameters. Repeated challenges will more faithfully mimic exposure conditions in endemic areas, and will also provide more insight into the duration of protection afforded by the vaccine. Traditionally, proof-of-concept for novel investigational vaccines is tested in large field trials in endemic areas. These can take considerable time depending on the incidence of infection in the control arm of the study. The objective of this R34 proposal is to plan a study in which proof-of-concept is tested early in the clinical development of new vaccines for hookworm, one of the most prevalent and important of the Neglected Tropical Diseases. The results of this trial will permit critical Go/No-Go decisions to be made on further development of the Na-GST-1 hookworm vaccine, prior to conducting larger, more costly Phase 2 and 3 trials.