Clinical trial NCT05038904: Preventing Anaphylaxis With Acalabrutinib
Official title: Preventing Life-Threatening Allergic Reactions With Acalabrutinib, an FDA-Approved Bruton's Tyrosine Kinase Inhibitor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Food Allergy
Food Allergy Peanut
Keywords: Anaphylaxis
Peanut allergy
Tree nut allergy
Hypersensitivity
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2021-09-09
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Highest Dose of Peanut That is Tolerated During Oral Food Challenge
timeFrame: Baseline and Day 2 of treatment
Secondary outcomes:
measure: Area Under the Curve Severity of Clinical Reaction to Peanut
timeFrame: Baseline and Day 2 of treatment
measure: Skin Prick Test Size to Peanut
timeFrame: Baseline and Day 2 of treatment
measure: Basophil Activation Testing
timeFrame: Baseline and Day 2 of treatment
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Bayview Medical Center
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Melanie C. Dispenza, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Suresh RV, Dunnam C, Vaidya D, Wood RA, Bochner BS, MacGlashan DW Jr, Dispenza MC. A phase II study of Bruton's tyrosine kinase inhibition for the prevention of anaphylaxis. J Clin Invest. 2023 Aug 15;133(16):e172335. doi: 10.1172/JCI172335.