Food Allergy, Food Allergy Peanut
Conditions
Keywords
Anaphylaxis, Peanut allergy, Tree nut allergy, Hypersensitivity
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.
Interventions
DRUGAcalabrutinib
100 mg oral capsule
Sponsors
AstraZeneca
Johns Hopkins University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Highest Dose of Peanut That is Tolerated During Oral Food Challenge | Baseline and Day 2 of treatment | 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
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve Severity of Clinical Reaction to Peanut | Baseline and Day 2 of treatment | 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 | Baseline and Day 2 of treatment | The skin prick test to peanut extract wheal area (in square mm) was measured at baseline and after treatment. |
| Basophil Activation Testing | Baseline and Day 2 of treatment | The percent of peripheral blood basophils activated by stimulation ex vivo with peanut extract was assessed by CD63 surface expression. |
Countries
United States
Participant flow
Recruitment details
All study visits occurred between December 2021 and October 2022. Patients were recruited from the Johns Hopkins University Allergy and Clinical Immunology outpatient clinic and through IRB-approved advertising on social media. Patients who responded to advertisements were initially screened by telephone to determine eligibility. If determined eligible, patients were remote consented prior to Visit 1 by teleconference in compliance with FDA 21 CFR Part 11.
Pre-assignment details
In this open-label trial, all eligible participants were given study drug.
Participants by arm
| Arm | Count |
|---|---|
| Acalabrutinib Participants will be given acalabrutinib (four doses of 100 mg of acalabrutinib to be taken orally twice daily).
Acalabrutinib: 100 mg oral capsule | 10 |
| Total | 10 |
Baseline characteristics
| Characteristic | Acalabrutinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 28 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 10 Participants |
| Serum peanut-specific IgE | 4.9 kUA/L |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 4 Participants |
| Sex/Gender, Customized Gender Female | 5 Participants |
| Sex/Gender, Customized Gender Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 5 / 10 |
| serious Total, serious adverse events | 3 / 10 |
Outcome results
Primary
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.
Time frame: Baseline and Day 2 of treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Acalabrutinib | Highest Dose of Peanut That is Tolerated During Oral Food Challenge | Baseline | 29 mg |
| Acalabrutinib | Highest Dose of Peanut That is Tolerated During Oral Food Challenge | Aftet treatment | 4,044 mg |
p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Baseline and Day 2 of treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Acalabrutinib | Area Under the Curve Severity of Clinical Reaction to Peanut | Baseline | 27.83 score on a scale*mg |
| Acalabrutinib | Area Under the Curve Severity of Clinical Reaction to Peanut | After treatment | 3.76 score on a scale*mg |
p-value: 0.0014t-test, 2 sided
Secondary
Basophil Activation Testing
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
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Acalabrutinib | Basophil Activation Testing | Baseline | 31.7 percent of basophils activated |
| Acalabrutinib | Basophil Activation Testing | After treatment | 1.56 percent of basophils activated |
Comparison: Participants' ex vivo basophil activation during acalabrutinib treatment was compared to their own baseline level.p-value: 0.002Wilcoxon (Mann-Whitney)
Secondary
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.
Time frame: Baseline and Day 2 of treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Acalabrutinib | Skin Prick Test Size to Peanut | Baseline | 126 square mm |
| Acalabrutinib | Skin Prick Test Size to Peanut | After treatment | 57.7 square mm |
p-value: 0.002Wilcoxon (Mann-Whitney)