Food Allergy, Peanut Allergy
Conditions
Keywords
peanut, allergy
Brief summary
The purpose of this study is to determine if treatment with omalizumab (Xolair, anti-IgE) can eliminate or reduce symptoms of peanut allergy.
Detailed description
The study will evaluate if omalizumab is an effective treatment for peanut allergy. In addition we will further evaluate the role of allergic cells (mast cells and basophils) and IgE in food allergy.
Interventions
DRUGomalizumab
omalizumab subcutaneously every 2-4 weeks depending on participant weight and total IgE
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Johns Hopkins University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Male or Female (non-pregnant), age 18-50 * Females must be: Surgically sterile (hysterectomy, bilateral oophorectomy, bilateral tubal ligation), OR postmenopausal (at least 1 year since last menses), OR using one of the following medically acceptable forms of birth control throughout the duration of the study: * Systemic contraceptives * Diaphragm with intravaginal spermicide * Cervical cap * Intrauterine device * Condom with intravaginal spermicide Females in certain categories (not sexually active, vasectomized partner) will be admitted at the discretion of the investigator on a case-by-case basis. Females, excluding those more than 1 year postmenopausal or who are surgically sterile, must have a negative urine pregnancy test at Visit 1 and other visits specified in this protocol. If a subject becomes pregnant during the study participation, they will be discharged from the study and followed for any adverse events until termination of the pregnancy or delivery is complete. Given that the drug is in pregnancy category B, we will follow the pregnant mother for any adverse events for the duration of the study. * Physician diagnosed peanut allergy OR convincing clinical history of peanut allergy with its onset in early childhood. * Positive puncture skin test to peanut greater than or equal to 3 mm diluent control * Positive ImmunoCAP to peanut ≥0.35 kU/L. * In vitro basophil responsiveness to peanut allergen, with greater than 20% histamine release or 10-19% if greater than 50% of an optimal anti-IgE response (at baseline visit). * Subjects must have a positive oral food challenge to peanut as defined by having objective signs of a clear allergic reaction at a cumulative dose of peanut protein \<1000 mg. Objective allergic signs may include oral urticaria, cutaneous urticaria, rhinorrhea, sneezing, coughing, wheezing, or vomiting.
Exclusion criteria
* Asthma with Forced Expiatory Volume in 1 second (FEV1) \< 80% predicted or severe persistent asthma per National Asthma Education and Prevention Program (NAEPP) Standards (2007 National Asthma Education and Prevention Program Expert Panel Report III guidelines) or poorly controlled asthma with oral corticosteroid use for exacerbation in last 6 months. * History of severe allergic reaction to peanut requiring intubation or ICU admission. * Late onset peanut allergy, defined as subjects who had previously tolerated peanut on a regular basis before their initial reaction. * Patients with biopsy proven eosinophilic enteropathy will be excluded. * Patients with total serum IgE levels less than 30 IU/mL or greater than 700 IU/mL at the time of enrollment will be excluded. * Patients with hematocrit \< 32%, White Blood Cell (WBC) count \<4000/microliter, platelet \< 75000/microliter, creatinine \> 141.4 micromolar/L, or Aspartate Aminotransferase (AST) \> 100 IU/L will be excluded if these abnormalities are present at the time of enrollment. * Body weight less than 30 kg or greater than 150 kg at enrollment will be excluded. * Patients with plans to become pregnant or breastfeed will be excluded from the study. Patients must indicate they will use methods to avoid pregnancy. * Other significant medical conditions (e.g., liver, gastrointestinal, kidney, cardiovascular, pulmonary disease, or blood disorders), which, in the opinion of the Investigator, make the subject unsuitable for induction of food reactions. * Current or prior use of omalizumab in the past 12 months. * Use of non-traditional forms of allergen immunotherapy (e.g., oral or sublingual) or immunomodulator (not including corticosteroids) or biologic therapy within the past year. * Use of beta-blockers (oral or ocular), angiotensin-converting enzyme (ACE) inhibitors, or angiotensin-receptor blockers (ARB) within 72 hours prior to either of the qualification Oral Food Challenge (OFC). * Use of antihistamines (within 3 days for short acting and 5 days for long acting) prior to the screening OFC. * Use of antihistamines (within 3 days for short acting and 5 days for long acting) prior to the study OFC. These procedures should be rescheduled when off antihistamines for the required time. * Inability to discontinue antihistamines for routine study tests. * History of ischemic cardiovascular disease (i.e., previous Myocardial Infarction, angina etc) or uncontrolled hypertension. * Significant upper respiratory tract infection (URI) within 7 days of any OFC; OFCs should be rescheduled within 7 days following resolution of URI. * Mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements. * Inability or unwillingness of a participant to give written informed consent or comply with study protocol. * Use of any investigational drugs within 8 weeks of participation. * Any contraindication to omalizumab including patients with a previous hypersensitivity to omalizumab.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced a Decrease in Pn-BHR Area Under the Curve (AUC) of > 80% Compared With Baseline Values Before Week 8 | up to 6 months | Presence or absence of this change |
| Percent Change in Peanut Specific Immunoglobulin E (IgE) From Baseline to After Pn-BHR Response | change from baseline to up to 6 months | percentage |
| Peanut Specific Immunoglobulin E (IgE) After Pn-BHR Response | up to 6 months | kU/L (range) |
| Total Immunoglobulin E (IgE) After Pn-BHR Response | up to 6 months | kU/L (range) |
| Dose of Peanut Protein Inducing Allergic Symptoms at Oral Food Challenge (OFC) 1 | up to 8 weeks | mg |
| Dose of Peanut Protein Inducing Allergic Symptoms at OFC 2 | up to 8 weeks | mg |
| Dose of Peanut Protein Inducing Allergic Symptoms at OFC 3 | up to 8 weeks | mg |
| Omalizumab Received Before OFC 2 | up to 6 months | Number of doses |
Countries
United States
Participant flow
Pre-assignment details
51 participants underwent screening history and laboratory evaluation. Of those, 14 underwent a screening food challenge and were randomized to subsequent arms.
Participants by arm
| Arm | Count |
|---|---|
| Open Label Omalizumab Group A Omalizumab was dosed according to package insert. Patients who have a decrease in peanut allergen induced basophil histamine release (Pn-BHR) to less than 20% of baseline will be assigned to this group.
omalizumab: omalizumab subcutaneously every 2-4 weeks depending on participant weight and total IgE | 5 |
| Open Label Omalizumab Group B Omalizumab was dosed according to package insert. Patients who do not have a decrease in peanut allergen induced basophil histamine release (Pn-BHR) to less than 20% of baseline will be assigned to this group.
omalizumab: omalizumab subcutaneously every 2-4 weeks depending on participant weight and total IgE | 9 |
| Total | 14 |
Baseline characteristics
| Characteristic | Open Label Omalizumab Group A | Open Label Omalizumab Group B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants | 9 Participants | 14 Participants |
| Region of Enrollment United States | 5 participants | 9 participants | 14 participants |
| Sex: Female, Male Female | 4 Participants | 7 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 9 |
| other Total, other adverse events | 0 / 5 | 0 / 9 |
| serious Total, serious adverse events | 0 / 5 | 0 / 9 |
Outcome results
Primary
Dose of Peanut Protein Inducing Allergic Symptoms at OFC 2
mg
Time frame: up to 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label Omalizumab Group A | Dose of Peanut Protein Inducing Allergic Symptoms at OFC 2 | 6500 mg |
| Open Label Omalizumab Group B | Dose of Peanut Protein Inducing Allergic Symptoms at OFC 2 | 6790 mg |
Primary
Dose of Peanut Protein Inducing Allergic Symptoms at OFC 3
mg
Time frame: up to 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label Omalizumab Group A | Dose of Peanut Protein Inducing Allergic Symptoms at OFC 3 | 8540 mg |
| Open Label Omalizumab Group B | Dose of Peanut Protein Inducing Allergic Symptoms at OFC 3 | 2455 mg |
Primary
Dose of Peanut Protein Inducing Allergic Symptoms at Oral Food Challenge (OFC) 1
mg
Time frame: up to 8 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label Omalizumab Group A | Dose of Peanut Protein Inducing Allergic Symptoms at Oral Food Challenge (OFC) 1 | 80 mg |
| Open Label Omalizumab Group B | Dose of Peanut Protein Inducing Allergic Symptoms at Oral Food Challenge (OFC) 1 | 80 mg |
Primary
Number of Participants Who Experienced a Decrease in Pn-BHR Area Under the Curve (AUC) of > 80% Compared With Baseline Values Before Week 8
Presence or absence of this change
Time frame: up to 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open Label Omalizumab Group A | Number of Participants Who Experienced a Decrease in Pn-BHR Area Under the Curve (AUC) of > 80% Compared With Baseline Values Before Week 8 | 5 Participants |
| Open Label Omalizumab Group B | Number of Participants Who Experienced a Decrease in Pn-BHR Area Under the Curve (AUC) of > 80% Compared With Baseline Values Before Week 8 | 9 Participants |
Primary
Omalizumab Received Before OFC 2
total mg
Time frame: up to 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label Omalizumab Group A | Omalizumab Received Before OFC 2 | 300 mg |
| Open Label Omalizumab Group B | Omalizumab Received Before OFC 2 | 900 mg |
Primary
Omalizumab Received Before OFC 2
Number of doses
Time frame: up to 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label Omalizumab Group A | Omalizumab Received Before OFC 2 | 1 number of doses |
| Open Label Omalizumab Group B | Omalizumab Received Before OFC 2 | 3 number of doses |
Primary
Peanut Specific Immunoglobulin E (IgE) After Pn-BHR Response
kU/L (range)
Time frame: up to 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label Omalizumab Group A | Peanut Specific Immunoglobulin E (IgE) After Pn-BHR Response | 2.1 kU/L |
| Open Label Omalizumab Group B | Peanut Specific Immunoglobulin E (IgE) After Pn-BHR Response | 30.5 kU/L |
Primary
Percent Change in Peanut Specific Immunoglobulin E (IgE) From Baseline to After Pn-BHR Response
percentage
Time frame: change from baseline to up to 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label Omalizumab Group A | Percent Change in Peanut Specific Immunoglobulin E (IgE) From Baseline to After Pn-BHR Response | 1.9 percentage change Peanut specific IgE |
| Open Label Omalizumab Group B | Percent Change in Peanut Specific Immunoglobulin E (IgE) From Baseline to After Pn-BHR Response | 32 percentage change Peanut specific IgE |
Primary
Total Immunoglobulin E (IgE) After Pn-BHR Response
kU/L (range)
Time frame: up to 6 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Open Label Omalizumab Group A | Total Immunoglobulin E (IgE) After Pn-BHR Response | 201 kU/L |
| Open Label Omalizumab Group B | Total Immunoglobulin E (IgE) After Pn-BHR Response | 129 kU/L |