Preventing Anaphylaxis With Acalabrutinib

Sponsor

Johns Hopkins University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05038904

Collaborator

AstraZeneca (Industry)

Enrollment

Location

Arm

24.5

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Food Allergy Food Allergy Peanut	Drug: Acalabrutinib	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 16, 2021

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acalabrutinib Participants will be given acalabrutinib (four doses of 100 mg of acalabrutinib to be taken orally twice daily).	Drug: Acalabrutinib 100 mg oral capsule Other Names: Calquence

Arm

Intervention/Treatment

Experimental: Acalabrutinib

Participants will be given acalabrutinib (four doses of 100 mg of acalabrutinib to be taken orally twice daily).

Drug: Acalabrutinib

100 mg oral capsule

Other Names:

Calquence

Outcome Measures

Primary Outcome Measures

Change in the highest dose of peanut or tree nut that is tolerated during oral food challenge before and after taking acalabrutinib, as defined by the PRACTALL consensus grading system [Baseline and Day 2]
Change in the highest dose of peanut or tree nut tolerated during oral food challenge before and after acalabrutinib treatment will be 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).

Secondary Outcome Measures

Change in severity of clinical reaction [Baseline and Day 2]
Change in the severity of reaction during oral food challenge before and after acalabrutinib treatment will be 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).
Change in skin prick test size change in wheal and/or flare diameter of skin prick tests to peanut or tree nut extract [Baseline and Day 2]
Skin prick testing will be performed on the forearm or back with peanut or tree nut extract. Wheal and flare diameter will be measured in millimeters.
Change in percent of basophils activated after stimulation with peanut/tree nut protein or anti-FcERI [Baseline and Day 2]
Basophil activation testing will be performed using whole blood samples stimulated with peanut or tree nut protein or anti-FcERI. The percent of activated basophils (those with CD63 surface upregulation) will be assessed by flow cytometry
Adverse reactions or toxicities from the study drug [Up to 3 months]
Participants will be monitored for adverse effects or toxicities from acalabrutinib treatment using laboratory testing and clinical exam.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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