Preventing Anaphylaxis With Acalabrutinib

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

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.

Study Overview

• Status: Completed
• Conditions: Food Allergy; Food Allergy Peanut
• Intervention / Treatment: Drug: Acalabrutinib

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Melanie C. Dispenza, MD, PhD, Johns Hopkins University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): December 16, 2021
• Primary Completion (Actual): December 8, 2022
• Study Completion (Actual): December 31, 2022

Study Registration Dates

• First Submitted: August 26, 2021
• First Submitted That Met QC Criteria: September 2, 2021
• First Posted (Actual): September 9, 2021

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Hypersensitivity; Peanut allergy; Anaphylaxis; Tree nut allergy
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Peanut Hypersensitivity; Food Hypersensitivity; Anaphylaxis; Antineoplastic Agents; Acalabrutinib
• Other Study ID Numbers: IRB00223615

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No