Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in Food Allergic Participants

Inclusion Criteria:

Individuals who meet all of the following criteria are eligible for enrollment as study participants:

1. Participant and/or parent/legal guardian must be able to understand and provideinformed consent and/or assent, as applicable;

2. Peanut allergic: participant must meet all of the following criteria to minimize thechance that the participant will develop natural tolerance to peanut over the courseof the study:

3. Positive skin prick test (SPT) defined as ≥4 mm wheal greater than salinecontrol) to peanut,

4. Positive peanut immunoglobulin E (IgE), ≥6 kUA/L, at Screening or within threemonths of Screening, determined by ImmunoCap, and

5. Positive double-blind placebo-controlled food challenge (DBPCFC), defined asexperiencing dose-limiting symptoms at a single dose of ≤100 mg of peanutprotein.

6. Allergic to at least two of the six other foods (milk, egg, wheat, cashew, hazelnut,walnut): each participant must meet all of the following criteria for at least twoof the six other foods to minimize the chance that the participant will developnatural tolerance to at least two of the six other foods over the course of thestudy:

7. Positive SPT (≥4 mm wheal) to food,

8. Positive food specific IgE (≥6 kUA/L) at Screening or within three months ofScreening, determined by ImmunoCap, and

9. Positive DBPCFC, defined as experiencing dose-limiting symptoms at a singledose of ≤300 mg of food protein.

10. With body weight (as measured at Screening) and total serum IgE level (as measuredwithin three months of Screening) suitable for omalizumab dosing;

11. If female of child-bearing potential, must have a negative urine or serum pregnancytest;

12. For women of childbearing potential, must agree to,during the treatment period andfor 60 days after the last dose of study drug:

• remain abstinent (refrain from heterosexual intercourse), or

• use acceptable contraceptive methods (barrier methods, or

• oral, injected, or implanted hormonal methods of contraception, or

• other forms of hormonal contraception that have comparable efficacy).

7. Plan to remain in the study area of an OUtMATCH clinical research unit (CRU) duringthe trial; and

8. Be willing to be trained on the proper use of an epinephrine autoinjector for theduration of the study.

Exclusion Criteria:

Individuals who meet any of the following criteria are not eligible for enrollment as study participants:

1. Inability or unwillingness of a participant and/or parent/legal guardian to givewritten informed consent and/or assent or comply with the study protocol;

2. Clinically significant laboratory abnormalities at Screening;

3. Dose-limiting symptoms to the placebo portion of the Screening DBPCFC;

4. Sensitivity or suspected/known allergy to any ingredients (including excipients) ofthe

• active or placebo oral food challenge (OFC) material,

• multi-allergen oral immunotherapy (OIT), or

• drugs related to omalizumab (e.g., monoclonal antibodies, polyclonal gammaglobulin).

• Note: Guidance for determination of sensitivity to excipients will bedetailed in the study's Manual of Procedures (MOP).

5. Poorly controlled atopic dermatitis (AD) at Screening, per the PrincipalInvestigator's PI's) discretion;

6. Poorly controlled or severe asthma/wheezing at Screening, defined by at least one ofthe following criteria:

7. Global Initiative for Asthma (GINA) criteria regarding asthma control latestguidelines,

8. History of two or more systemic corticosteroid courses within six months ofScreening or one course of systemic corticosteroids within three months ofScreening to treat asthma/wheezing,

9. Prior intubation/mechanical ventilation for asthma/wheezing,

10. One hospitalization or Emergency Department (ED) visit for asthma/wheezingwithin six months of Screening,

11. Forced expiratory volume in one second (FEV1) <80 percent of predicted orFEV1/forced vital capacity (FVC) <75 percent, with or without controllermedications (only for participants who are aged seven years or older and areable to perform spirometry), or

12. Inhaled corticosteroid (ICS) dosing of >500 mcg daily fluticasone (orequivalent ICS based on the National Institutes of Health, National Heart,Lung, and Blood Institute (NHLBI) dosing chart).

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

14. Treatment with a burst of oral, intramuscular (IM), or intravenous (IV) steroids ofmore than two days for an indication other than asthma/wheezing within 30 days ofScreening;

15. Currently receiving oral, intramuscular, or intravenous corticosteroids, tricyclicantidepressants, or beta-blockers (oral or topical);

16. Past or current history of eosinophilic gastrointestinal (GI) disease within threeyears of Screening;

17. Past or current history of cancer, or currently being investigated for possiblecancer;

18. Previous adverse reaction to omalizumab;

19. Past or current history of any immunotherapy to any of the foods being treated inthis study (e.g., OIT, sublingual immunotherapy [SLIT], EPIT) within 6 months ofScreening;

20. Treatment with monoclonal antibody therapy, such as omalizumab (Xolair®), dupilumab (Dupixent®), benralizumab (Fasenra™), mepolizumab (Nucala®), reslizumab (Cinqair®),or other immunomodulatory therapy within six months of Screening;

21. Currently on "build-up phase" of inhalant allergen immunotherapy (i.e., has notreached maintenance dosing). Note: Individuals tolerating maintenance allergenimmunotherapy can be enrolled;

22. Inability to discontinue antihistamines for the minimum wash-out periods requiredfor SPTs,or OFCs;

23. Current participation in another therapeutic or interventional clinical trial orparticipation within 90 days of Screening;

24. Use of investigational drugs within 24 weeks of Screening;

25. Pregnant or breastfeeding, or intending to become pregnant during the study orwithin 60 days after the last dose of omalizumab or placebo for omalizumab;

26. Has a first-degree relative already enrolled in the study; or

27. Past or current medical problems (e.g., severe latex allergy), history of otherchronic diseases (other than asthma/wheezing, AD, or rhinitis) requiring therapy (e.g., heart disease, diabetes), findings from physical assessment, or abnormalitiesin clinical laboratory testing that are not listed above, which, in the opinion ofthe PI, may:

• pose additional risks from participation in the study,

• may interfere with the participant's ability to comply with study requirements,or

• may impact the quality or interpretation of the data obtained from the study.