Preventing Anaphylaxis With Acalabrutinib
Primary Purpose
Food Allergy, Food Allergy Peanut
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Acalabrutinib
Sponsored by
About this trial
This is an interventional treatment trial for Food Allergy focused on measuring Anaphylaxis, Peanut allergy, Tree nut allergy, Hypersensitivity
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
Sites / Locations
- Johns Hopkins Bayview Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Acalabrutinib
Arm Description
Participants will be given acalabrutinib (four doses of 100 mg of acalabrutinib to be taken orally twice daily).
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
Basophil Activation Testing
The percent of peripheral blood basophils activated by stimulation ex vivo with peanut extract was assessed by CD63 surface expression.
Full Information
NCT ID
NCT05038904
First Posted
August 26, 2021
Last Updated
September 27, 2023
Sponsor
Johns Hopkins University
Collaborators
AstraZeneca
1. Study Identification
Unique Protocol Identification Number
NCT05038904
Brief Title
Preventing Anaphylaxis With Acalabrutinib
Official Title
Preventing Life-Threatening Allergic Reactions With Acalabrutinib, an FDA-Approved Bruton's Tyrosine Kinase Inhibitor
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
December 16, 2021 (Actual)
Primary Completion Date
December 8, 2022 (Actual)
Study Completion Date
December 31, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
AstraZeneca
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Food Allergy, Food Allergy Peanut
Keywords
Anaphylaxis, Peanut allergy, Tree nut allergy, Hypersensitivity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Acalabrutinib
Arm Type
Experimental
Arm Description
Participants will be given acalabrutinib (four doses of 100 mg of acalabrutinib to be taken orally twice daily).
Intervention Type
Drug
Intervention Name(s)
Acalabrutinib
Other Intervention Name(s)
Calquence
Intervention Description
100 mg oral capsule
Primary Outcome Measure Information:
Title
Highest Dose of Peanut That is Tolerated During Oral Food Challenge
Description
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.
Time Frame
Baseline and Day 2 of treatment
Secondary Outcome Measure Information:
Title
Area Under the Curve Severity of Clinical Reaction to Peanut
Description
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.
Time Frame
Baseline and Day 2 of treatment
Title
Skin Prick Test Size to Peanut
Description
The skin prick test to peanut extract wheal area (in square mm) was measured at baseline and after treatment.
Time Frame
Baseline and Day 2 of treatment
Title
Basophil Activation Testing
Description
The percent of peripheral blood basophils activated by stimulation ex vivo with peanut extract was assessed by CD63 surface expression.
Time Frame
Baseline and Day 2 of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melanie C. Dispenza, MD, PhD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Bayview Medical Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
37384412
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.
Results Reference
result
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Preventing Anaphylaxis With Acalabrutinib
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