Beginning to Assess an Appropriate CONtrol for Oral Food Challenges in Alpha-Gal Syndrome (CoFAR-13) - BeACON4AG

Official title

Beginning to Assess an Appropriate CONtrol for Oral Food Challenges in Alpha-Gal Syndrome (CoFAR-13)

Overview

This is a multisite, randomized, double-blind, controlled cross-over trial with detailed characterization of participants with varying clinical sub-phenotypes of Alpha-gal Syndrome (AGS) who are then evaluated by oral food challenges with alpha-gal Knock Out (KO) pork versus Wild Type (WT) pork. Each participant will serve as their own control and ingest both alpha-gal-KO and WT pork on different days, with a minimum of an 8-day washout period between oral food challenges. The primary objective is to determine whether the odds of positive challenges among participants with suspected alpha-gal syndrome are lower with alpha-gal Knock Out (KO) pork as compared to Wild Type (WT) pork during Double Blind Food Challenge (DBFC)

Interventions

• Diagnostic test DBFC with 150g of Alpha-gal Knock Out (KO) pork
  Each participant will serve as their own control and ingest both alpha-gal-KO and WT pork on different days, with a minimum of an 8-day washout period between oral food challenges
• Diagnostic test DBFC with 150g of Wild Type (WT) pork
  Each participant will serve as their own control and ingest both alpha-gal-KO and WT pork on different days, with a minimum of an 8-day washout period between oral food challenges

Primary outcome measures

• Positive Double Blind Food Challenge (DBFC) result to 150 grams of either alpha-gal knockout (KO) pork or wild type (WT) pork. [Time frame: At Visit 1 (within 2 months of screening) or Visit 2 (between 8 and 30 days of Visit 1)]

Secondary outcome measures (3)

• Alpha-gal sub-phenotype as determined by symptoms resulting from Double Blind Food Challenge (DBFC) to wild-type (WT) pork. [Time frame: At Visit 1 (within 2 months of screening) or Visit 2 (between 8 and 30 days of Visit 1)]
• Gastrointestinal Symptom Rating Scale - Irritable Bowel Syndrome (GSRS-IBS) scores in response to 150 grams of Knock Out (KO) or Wild Type (WT) pork at each challenge visit [Time frame: At 7 days following completion of Double Blind Food Challenge (DBFC) at Visit 1 (within 2 months of screening) or Visit 2 (between 8 and 30 days of Visit 1)]
• Urticaria Activity Score (UAS7) in response to 150 grams of Knock Out (KO) or Wild Type (WT) pork at each challenge visit. [Time frame: At 7 days following completion of Double Blind Food Challenge (DBFC) at Visit 1 (within 2 months of screening) or Visit 2 (between 8 and 30 days of Visit 1)]

Eligibility criteria

Inclusion criteria

• Able to understand and provide informed consent and/or have a parent or guardian able to understand and provide informed consent. Participants 12-17 years old must be able to provide assent
• Participants who are willing to complete study procedures and follow-up
• Have clinical history consistent with Alpha-gal Syndrome (AGS)
• Have alpha-gal-specific Immunoglobin E (IgE) >= 0.1KU/L at screening
• Report reaction consistent with AGS within the previous 24 months (prior to enrollment)
• If with reproductive potential, agree to be abstinent or use an US Food and Drug Administration (FDA) approved method of birth control for the duration of the study
• Willing to be trained on the proper use of a device for the self-administration of epinephrine (i.e., autoinjector or intra-nasal spray) and willing to have two doses available for the duration of the study

Exclusion criteria

• Unwilling to consume pork (native/wild type or genetically modified to no longer contain alpha-gal) during Double Blind Food Challenge (DBFC)
• Have underlying health conditions suggesting that participants should not undergo an oral food challenge, including conditions that may be exacerbated by oral food challenge or treatment with epinephrine (e.g., history of ischemic heart disease, uncontrolled asthma, or cardiac arrhythmia)
• Likely to move away from the study site prior to completion of follow up or do not have regular access to a phone
• Have a history of severe anaphylaxis in response to pork or alpha-gal ingestion, defined as neurologic compromise or requiring intubation or cardiovascular compromise defined as myocardial infarction or other clinically significant cardiovascular events
• Unwilling or unable to stop use of medications that may interfere with oral food challenge interpretation, reaction, or treatment for 5 half-lives prior to the challenge (e.g., antihistamines, beta blockers, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
• Have used systemic immunomodulators (including biologics and monoclonal antibody therapy) within 6 months before study entry
• Have underlying health conditions that may increase the chance of false positive challenges (e.g., inflammatory bowel disease, chronic urticaria, systemic mastocytosis, and mast cell activating syndrome)
• Have used systemic steroids within 4 weeks of study entry
• Have used any investigational agent within 6 months of study entry
• Are on build-up of immunotherapy such as Antigen-based Immunotherapy (AIT), Oral Immunotherapy (OIT), Sublingual Immunotherapy (SLIT), or Epicutaneous Immunotherapy (EPIT)
• Have reacted to mammalian products with onset of symptoms within 30 minutes of oral ingestion
• Have current, diagnosed, mental illness or current, diagnosed or self-reported drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements
• Are pregnant or plan to become pregnant during the course of the study
• Have past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements, and/or may impact the quality or interpretation of the data obtained from the study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Diagnostic

Study locations

United States · 4 centers

• Arkansas Children's Hospital Research Institute: Department of Pediatrics, Allergy & Immun — Little Rock
• North Carolina Children's Hospital: Department of Pediatrics, Division of Allergy, Immunol — Chapel Hill
• Vanderbilt University Medical Center: Division of Pediatric Allergy, Immunology, and Pulmo — Nashville
• University of Virginia Health System: Division of Asthma & Immunology — Charlottesville

Identifiers

NCT: NCT07611435 · DAIT CoFAR-13

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗