Arkansas Center for Food Allergy Research (ArCOFAR) - PROJECT SUMMARY/ABSTRACT Alpha-gal syndrome (AGS) is an IgE-mediated allergy syndrome with the key allergenic epitope denoted as the oligosaccharide galactose-alpha-1, 3-galactose (alpha-gal) found in non-primate mammalian meat and mammal- derived products. Patients with AGS are known to be potentially at risk for a wide variety of clinical presentations, including delayed onset allergic reactions with exposure to alpha-gal in foods (including mammalian meat, gelatin, dairy), medication ingredients, and medical devices. Reactions to consumption of mammalian meat products in AGS patients manifest as IgE-mediated allergic reactions typically with a delayed onset by 2-6 hours from exposure. Reported reactions are associated with highly variable symptom severity including reports of anaphylaxis in some while others report cutaneous or GI symptoms only. There is also a high prevalence of sensitization to alpha-gal without symptoms that has been observed in populations with exposure to the relevant ticks. In IgE-mediated food allergy, the reference standard for diagnosis is prospective oral food challenges; however, patients with positive IgE against alpha-gal have only rarely undergone oral food challenges. The field is lacking in tests and biomarkers of disease, including appropriate alpha-gal-free control products and standardized methods for oral food challenge, that define AGS with diagnostic accuracy and predict disease activity. Recent FDA-approval of an alpha-gal knock-out (KO) pig as a food source animal (Revivicor) and the commercial availability of pork products derived from these alpha- gal KO pigs (GalSafe™) presents a unique opportunity to understand mechanistically whether the presence of alpha-gal allergen in porcine mammalian tissues is both necessary and sufficient to trigger reactions in participants with positive alpha-gal-specific IgE whose clinical history is consistent with allergy. It also presents an opportunity to identify whether this product could serve as a control for future clinical trials of therapeutic strategies in AGS. Oral food challenges with pork from alpha-gal KO and wild-type (WT) pigs also present an opportunity to identify mechanistic biomarkers that might characterize a reaction to alpha-gal containing meat. The Beginning to Assess an Appropriate Control for Oral Food Challenges in Alpha-Gal Syndrome (BeACON4AG) Trial, also known as CoFAR-13, is a 4-center trial conducted within the Consortium for Food Allergy Research (CoFAR) network and lead by Vanderbilt University Medical Center (PI, L. Bacharier) with inclusion of 3 other centers located within regions of high prevalence of AGS, including the University of Arkansas for Medical Sciences and Arkansas Children’s Hospital (site PI, S. Jones), the University of North Carolina Chapel Hill (site PI, S. Commins) and the University of Virginia (site PI: J. Wilson). The study is designed to assess the efficacy and safety of alpha-gal KO pork product as a control for double-blind food challenges (DBFC) using a Phase II, randomized, multisite, two-period, two-sequence, double-blind, controlled cross-over trial in participants ages 12 to 50 years old with suspected AGS. The study’s primary objective is to determine whether the proportion of positive challenges among participants with suspected AGS is lower with alpha-gal KO pork product as compared to WT pork during DBFC. Secondary objectives include focused evaluations among sub- phenotypes of AGS, safety, and identification of biomarkers. This Administrative Supplement is requested for the Arkansas Center for Food Allergy Research (U01AI181962) as a participating site for CoFAR network trials. This request is specific to the CoFAR-13 network trial and encompasses several purposes: 1) secure acquisition of alpha-gal containing WT and alpha-gal KO (GalSafeTM) pork sources for testing via blinded oral food challenges, 2) supply materials to all study sites for safe preparation of pork products and c
