Preventing Anaphylaxis With Acalabrutinib

Study Overview
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Brief Summary
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Food allergy is a potentially life-threatening condition, and its prevalence continues to increase despite public health efforts. There are currently no known therapies that can reliably prevent food-induced anaphylaxis. This is an open-label study designed to determine the ability acalabrutinib to prevent signs and symptoms of anaphylaxis during an oral food challenge in food-allergic adults.

Detailed Description
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Approximately 15 million people (including 8% of children) in the US have a food allergy and are at risk for life-threatening systemic reactions to foods. There is an unmet need for treatments capable of preventing such reactions. This is a phase II, single-center, open label trial involving the use of acalabrutinib (brand name Calquence®) to prevent food-induced anaphylaxis in adults with food allergy. Acalabrutinib is FDA-approved to treat certain medical conditions, but it is not approved to treat allergies. Adult participants with a physician-diagnosed food allergy to peanut and/or tree nuts will be enrolled. These participants will undergo an oral food challenge to peanut or a tree nut under close physician supervision to determine participants' baseline reactivity. After a rest period, the participants will take 4 oral doses of acalabrutinib 100 mg, and then repeat the oral food challenge to see if acalabrutinib will reduce participants' reactivity to peanut or tree nuts.

Official Title
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Preventing Life-Threatening Allergic Reactions With Acalabrutinib, an FDA-Approved Bruton's Tyrosine Kinase Inhibitor

Conditions
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Food Allergy, Food Allergy Peanut

Intervention / Treatment
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* Drug: Acalabrutinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of immunoglobulin E (IgE)-mediated food allergy to peanut or tree nut Positive skin prick test to the trigger food (either peanut or tree nut) Objective clinical reaction to the food allergen during baseline oral food challenge Women of child bearing potential must agree to two forms of highly effective contraception (hormonal, device, or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 7 days following completion of acalabrutinib therapy. Ability to understand and the willingness to sign a written informed consent Ability to clearly understand and speak English at an 8th grade reading level Exclusion Criteria: Participants who have been on immunomodulatory therapies or oral corticosteroids within 1 month prior to enrollment Participants with symptoms consistent with food reactions other than type 1 hypersensitivity History of allergic reaction to acalabrutinib History of idiopathic urticaria, dermatographism, idiopathic or unexplained anaphylaxis, or anaphylaxis (to foods or otherwise) resulting in intubation, prolonged hypotension, or neurological sequelae- History of cardiovascular disease History of a bleeding disorder, or those currently taking blood thinners History of stroke History of gastrointestinal ulcer History of cancer (other than skin cancer) Positive HIV status or history of other immunodeficiency Active or latent Hepatitis B or C infection based on laboratory testing Currently pregnant or nursing Current use of proton pump inhibitors (Note: participants currently receiving proton pump inhibitors who switch to H2-receptor antagonists or other antacids are eligible for enrollment to this study). Active significant infection Major surgical procedure within 28 days of enrollment Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura Difficulty swallowing oral medication, or significant gastrointestinal disease that would limit absorption of oral medication Concurrent participation in another therapeutic clinical trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acalabrutinib<br>Participants will be given acalabrutinib (four doses of 100 mg of acalabrutinib to be taken orally twice daily). | Drug: Acalabrutinib<br>* 100 mg oral capsule<br>* Other names: Calquence;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Highest Dose of Peanut That is Tolerated During Oral Food Challenge | The highest dose of peanut protein (in mg) tolerated during oral food challenge before and after acalabrutinib treatment was determined by assessing clinical symptoms and physcial exam findings in each organ system during the challenge. Symptoms were given a numeric score based on the American Academy of Allergy, Asthma, and Immunology/European Academy of Allergy and Clinical Immunology PRACTALL consensus system to grade symptom severity and the likelihood of their representing a true objective clinical reaction to peanut. | Baseline and Day 2 of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve Severity of Clinical Reaction to Peanut | The severity of participants' cliinical reaction during oral food challenge before and after acalabrutinib treatment was determined using the American Academy of Allergy, Asthma, and Immunology/European Academy of Allergy and Clinical Immunology PRACTALL consensus system to grade objective clinical findings on physical exam on a scale of 0 (absent) to 3 (severe) in 9 different organ system categories. Total symptom scores for each food dose ranged from a minimum if 0 (no symptoms) to 27 (severe objective symptoms in all organ systems), and the area under the curve for all scores during the food challenge were calculated for each participant. | Baseline and Day 2 of treatment | 
| Skin Prick Test Size to Peanut | The skin prick test to peanut extract wheal area (in square mm) was measured at baseline and after treatment. | Baseline and Day 2 of treatment | 
| Basophil Activation Testing | The percent of peripheral blood basophils activated by stimulation ex vivo with peanut extract was assessed by CD63 surface expression. | Baseline and Day 2 of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anaphylaxis, Peanut allergy, Tree nut allergy, Hypersensitivity