Clinical Study Using Biologics to Improve Multi OIT Outcomes (COMBINE)

Inclusion Criteria:

• Age 4 through 55 years (inclusive).

• Clinical history of peanut allergy and 1 or 2 additional foods from the followingfoods: milk, almond, shellfish, fish, cashew, hazelnut, egg, walnut, sesame seeds,soy, and wheat. Allergy to milk and egg is defined as unable to tolerate both cookedand uncooked forms.

• Positive allergy test determined by:

• ImmunoCAP serum IgE level >4 kUA/L for each allergen within the past 12 months OR

• Skin prick test (SPT) ≥6 mm wheal diameter to each allergen.

• A clinical reaction during a DBPCFC to small doses of food defined as a cumulativedose of =/<444 mg food protein.

• No clinical reaction observed during the placebo (oat) challenge.

• Subject and/or parent guardian must be able to understand and provide informedconsent.

• Written informed consent from adult participants.

• Written informed consent from parent/guardian for minor participants.

• Written assent from minor participants as appropriate (e.g., at and above the age of 7 years).

• Use of effective birth control by female participants of childbearing potential.

Exclusion Criteria:

• History of cardiovascular disease, including uncontrolled or inadequately controlledhypertension.

• Individuals less than 15 kg in weight at start of the study

• History of severe anaphylaxis to participant-specific foods that will be used inthis study, defined as neurological compromise or requiring intubation.

• History of chronic disease (other than asthma, atopic dermatitis or allergicrhinitis) that is, or is at significant risk of becoming, unstable or requiring achange in chronic therapeutic regimen.

• History of eosinophilic esophagitis (EoE), another eosinophilic gastrointestinaldisease, chronic, recurrent, or severe gastroesophageal reflux disease (GERD),symptoms of dysphagia (e.g., difficulty swallowing, food "getting stuck"), orrecurrent gastrointestinal symptoms of undiagnosed etiology.

• Severe asthma (NAEPP EPR-3 Medication Criteria Steps 5 or 6)

• Mild or moderate asthma (NAEPP EPR-3 Medication Criteria Steps 1-4), if uncontrolledor difficult to control.

• Uncontrolled asthma as evidenced by:

• FEV1 < 80% of predicted, or ratio of FEV1 to forced vital capacity (FEV1/FVC) < 75% of predicted, with or without controller medications (only for age 6 orgreater and able to do spirometry reliably. If unable to do spirometry, PEF of >80% is acceptable) or;

• One overnight admission to a hospital in the past year for asthma or;

• Emergency room (ER) visit for asthma within six months prior to screening.

• Inability to tolerate biological (antibody) therapies.

• Use of immunomodulator therapy (not including corticosteroids).

• Use of beta-blockers (oral), angiotensin-converting enzyme (ACE) inhibitors,angiotensin-receptor blockers (ARB) or calcium channel blockers.

• Current participation or within the last 4 months in any other interventional study.

• Pregnancy or lactation.

• Allergy to oat (placebo in DBPCFC).

• Use of investigational drugs within 16 weeks of participation.

• In build up phase of immunotherapy for aeroallergens or venom.