Trial Outcomes & Findings for Preventing Anaphylaxis With Acalabrutinib (NCT NCT05038904)

Last Updated: 2023-09-28

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Baseline and Day 2 of treatment

Results posted on

2023-09-28

Participant Flow

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.

In this open-label trial, all eligible participants were given study drug.

Participant milestones

Participant milestones
Measure	Acalabrutinib All participants received four oral doses of 100 mg of acalabrutinib twice daily.
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Preventing Anaphylaxis With Acalabrutinib

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Acalabrutinib n=10 Participants Participants will be given acalabrutinib (four doses of 100 mg of acalabrutinib to be taken orally twice daily). Acalabrutinib: 100 mg oral capsule
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	10 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	28 years n=5 Participants
Sex/Gender, Customized Gender · Male	5 Participants n=5 Participants
Sex/Gender, Customized Gender · Female	5 Participants n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	10 Participants n=5 Participants
Serum peanut-specific IgE	4.9 kUA/L n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 2 of treatment

Outcome measures

Outcome measures
Measure	Acalabrutinib n=10 Participants Participants will be given acalabrutinib (four doses of 100 mg of acalabrutinib to be taken orally twice daily). Acalabrutinib: 100 mg oral capsule
Highest Dose of Peanut That is Tolerated During Oral Food Challenge Baseline	29 mg Interval 1.0 to 444.0
Highest Dose of Peanut That is Tolerated During Oral Food Challenge Aftet treatment	4,044 mg Interval 444.0 to

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Acalabrutinib n=10 Participants Participants will be given acalabrutinib (four doses of 100 mg of acalabrutinib to be taken orally twice daily). Acalabrutinib: 100 mg oral capsule
Area Under the Curve Severity of Clinical Reaction to Peanut Baseline	27.83 score on a scale*mg Interval 15.91 to 39.75
Area Under the Curve Severity of Clinical Reaction to Peanut After treatment	3.76 score on a scale*mg Interval 0.12 to 7.39

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Acalabrutinib n=10 Participants Participants will be given acalabrutinib (four doses of 100 mg of acalabrutinib to be taken orally twice daily). Acalabrutinib: 100 mg oral capsule
Skin Prick Test Size to Peanut Baseline	126 square mm Interval 27.5 to 480.0
Skin Prick Test Size to Peanut After treatment	57.7 square mm Interval 0.0 to 345.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Acalabrutinib n=10 Participants Participants will be given acalabrutinib (four doses of 100 mg of acalabrutinib to be taken orally twice daily). Acalabrutinib: 100 mg oral capsule
Basophil Activation Testing Baseline	31.7 percent of basophils activated Interval 3.5 to 70.7
Basophil Activation Testing After treatment	1.56 percent of basophils activated Interval 0.0 to 4.6

Adverse Events

Acalabrutinib

Serious events: 3 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Acalabrutinib n=10 participants at risk All participants who received acalabrutinib
Injury, poisoning and procedural complications Sports-related concussion	20.0% 2/10 • Number of events 2 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.
Injury, poisoning and procedural complications Sports-related injury	10.0% 1/10 • Number of events 1 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.
Injury, poisoning and procedural complications Emergency room visit after baseline food challenge	10.0% 1/10 • Number of events 1 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.

Other adverse events

Other adverse events
Measure	Acalabrutinib n=10 participants at risk All participants who received acalabrutinib
Blood and lymphatic system disorders Neutropenia	10.0% 1/10 • Number of events 1 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.
Blood and lymphatic system disorders Anemia	20.0% 2/10 • Number of events 2 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.
Hepatobiliary disorders Elevated liver function tests	10.0% 1/10 • Number of events 1 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.
Blood and lymphatic system disorders Eosinophilia	10.0% 1/10 • Number of events 1 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.
Infections and infestations COVID-19 infection	10.0% 1/10 • Number of events 1 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.
Blood and lymphatic system disorders Leukocytosis	10.0% 1/10 • Number of events 1 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.
General disorders Hypokalemia	10.0% 1/10 • Number of events 1 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.
General disorders Hypoalbuminemia	10.0% 1/10 • Number of events 1 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.
Metabolism and nutrition disorders Hyperglycemia	20.0% 2/10 • Number of events 2 • 6 months This study followed the FDA Guidance For Industry ("Toxicity grading scale for healthy adult and adolescent volunteers enrolled in preventative vaccine clinical trials") grading system for adverse events.

Additional Information

Melanie C. Dispenza, MD, PhD

Johns Hopkins University School of Medicine

Phone: 410-550-2301

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place