Peanut Hypersensitivity
Conditions
Keywords
Peanut, Allergy, Hypersensitivity
Brief summary
The purpose of this study is to determine whether the addition of anti-IgE treatment will make peanut oral immunotherapy safer, more tolerable, and more effective in treating peanut allergy.
Detailed description
The goal of this proposal is to produce a new treatment that would benefit subjects who have peanut allergy by lowering the risk of anaphylactic reactions (desensitization), and changing the peanut-specific immune response in subjects who have peanut allergy (tolerance). This project is designed to study if peanut oral immunotherapy (OIT) will desensitize subjects with peanut hypersensitivity by regulating their oral and systemic immune reactivity and cause long-term tolerance. This study will augment other ongoing studies by looking at whether anti-IgE therapy can reduce side effects and allow for an accelerated build up phase. Peanut allergic patients greater than 12 years old will undergo omalizumab (anti-IgE) treatment for 4 months prior to peanut OIT, and they will continue omalizumab until one month after maintenance therapy. Each subject will have an initial desensitization phase over 2 days to a goal of 950 mg of peanut powder followed by a build up phase over 4 months to goal maintenance dose of 8000 mg peanut powder. They will be randomized to continue maintenance for 12 or 24 months. They will then have an oral food challenge (OFC) immediately after stopping peanut OIT to test for desensitization. Four weeks later, off OIT, another food challenge will be done to assess tolerance. Outcome variables of interest include results of the OFCs, pre and post skin tests, CAP-FEIA values and basophil studies. These results will be compared between the starting point and the patient at the end of the study using appropriate statistical analysis.
Interventions
Peanut flour taken by mouth, given every day. Dose ranges from 0.2mg of peanut flour to 8000mg of peanut flour during the maintenance phase.
DRUGOmalizumab
Omalizumab (anti-IgE) will be given for 4 months prior to starting oral immunotherapy. The medication is given as a subcutaneous injection with dose based on total IgE levels and weight at the beginning of the study. This medication is given for a total of 10 months.
Sponsors
Genentech, Inc.
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 12 years and above of either sex, any race, any ethnicity at the time of the initial visit * The presence of IgE specific to peanuts (a positive skin prick test to peanuts (diameter of wheal \> 3.0 mm) and a positive in vitro IgE \[CAP-FEIA\] \> 5 kUA/L * A history of significant clinical symptoms (urticaria, angioedema, rhinorrhea, nasal congestion, pruritis, sneezing, abdominal pain, emesis, diarrhea, wheezing, shortness of breath, lip/tongue swelling, throat itching, throat swelling, impending sense of doom) occurring within 60 minutes after ingesting peanuts * Provide signed informed consent * Women who are sexually active, must agree to use appropriate contraceptive measures for the duration of the study and for 9 months afterwards
Exclusion criteria
* History of severe anaphylaxis to peanut or omalizumab as defined by hypoxia, hypotension, or neurological compromise (Cyanosis or oxygen saturation \< 92% at any stage, hypotension, confusion, collapse, loss of consciousness; or incontinence) * Currently participating in a study using an investigational new drug * Participation in any interventional study for the treatment of food allergy in the past 12 months * Subjects with a known oat or wheat (because of potential cross contamination with oat) food allergy will be excluded * Poor control or persistent activation of atopic dermatitis * Moderate to severe persistent asthma * Currently being treated with greater than medium daily doses of inhaled corticosteroids, as defined by the National Heart Lung and Blood Institute (NHLBI) guidelines * Inability to discontinue antihistamines for skin testing and oral food challenges (OFCs) * History of other serious underlying disease (i.e., heart disease, diabetes, etc.) * Women who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Subjects Who Pass the 20gm Peanut Flour (~50% Peanut Protein) Oral Food Challenge 2-4 Weeks After Discontinuing Peanut OIT Therapy | approximately 24 or 36 months | The primary efficacy outcome of the study is to evaluate whether the addition of anti-IgE therapy using Xolair to peanut oral immunotherapy is able to induce clinical tolerance as measured by passing an oral food challenge to 20 grams of peanut flour, 2-4 weeks after discontinuing peanut OIT therapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Percentage of Subjects Who Tolerate the Initial Desensitization Day(s) to 950mg of Peanut Flour. | 4 months | A secondary efficacy outcome of the study is to evaluate whether the addition of anti-IgE therapy using Xolair to a peanut oral immunotherapy protocol allows for a higher amount of peanut tolerated after the rush desensitization phase, thereby reducing the duration of buildup phase and achieving maintenance dosing more rapidly |
| The Percentage of Subjects Who Pass the 20gm Peanut Flour (~50% Peanut Protein) Oral Food Challenge Following the Desensitization Phase of the Study | approximately 24 or 36 months | A secondary efficacy outcome of the study is to evaluate whether the addition of anti-IgE therapy using Xolair to peanut oral immunotherapy is able to induce clinical desensitization as measured by passing an oral food challenge to 20 grams of peanut flour on the final day of peanut OIT dosing. |
| Incidence of All Serious Adverse Events During the Study | approximately 24 or 36 months | A secondary safety outcome of the study is to determine the frequency of SAEs during oral immunotherapy in order to assess whether the addition of anti-IgE therapy using Xolair to peanut oral immunotherapy can reduce the number of SAEs that occur during oral immunotherapy when compared to previously published results |
| Incidence of Side Effects During Initial Escalation and Build up Phase of Peanut Oral Immunotherapy | approximately 24 or 36 months | The primary safety outcome of the study is to determine the frequency of side effects during oral immunotherapy in order to assess whether the addition of anti-IgE therapy using Xolair to peanut oral immunotherapy can reduce the number of allergic symptoms that occur during oral immunotherapy when compared to previously published results |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 12 Month Maintenance of PnOIT Subjects randomized to receive maintenance oral peanut immunotherapy (PnOIT) for 12 months prior to the desensitization food challenge. | 7 |
| 24 Month Maintenance of PnOIT Subjects randomized to receive maintenance oral peanut immunotherapy (PnOIT) for 24 months prior to the desensitization food challenge. | 6 |
| Total | 13 |
Baseline characteristics
| Characteristic | 24 Month Maintenance of PnOIT | 12 Month Maintenance of PnOIT | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 6 Participants | 6 Participants | 12 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Continuous | 14.1 years | 14.4 years | 14.4 years |
| Region of Enrollment United States | 6 Participants | 7 Participants | 13 Participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 6 |
| other Total, other adverse events | 4 / 7 | 3 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 6 |
Outcome results
Primary
The Percentage of Subjects Who Pass the 20gm Peanut Flour (~50% Peanut Protein) Oral Food Challenge 2-4 Weeks After Discontinuing Peanut OIT Therapy
The primary efficacy outcome of the study is to evaluate whether the addition of anti-IgE therapy using Xolair to peanut oral immunotherapy is able to induce clinical tolerance as measured by passing an oral food challenge to 20 grams of peanut flour, 2-4 weeks after discontinuing peanut OIT therapy
Time frame: approximately 24 or 36 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 12 Month Maintenance of PnOIT | The Percentage of Subjects Who Pass the 20gm Peanut Flour (~50% Peanut Protein) Oral Food Challenge 2-4 Weeks After Discontinuing Peanut OIT Therapy | 3 Participants |
| 24 Month Maintenance of PnOIT | The Percentage of Subjects Who Pass the 20gm Peanut Flour (~50% Peanut Protein) Oral Food Challenge 2-4 Weeks After Discontinuing Peanut OIT Therapy | 1 Participants |
Secondary
Incidence of All Serious Adverse Events During the Study
A secondary safety outcome of the study is to determine the frequency of SAEs during oral immunotherapy in order to assess whether the addition of anti-IgE therapy using Xolair to peanut oral immunotherapy can reduce the number of SAEs that occur during oral immunotherapy when compared to previously published results
Time frame: approximately 24 or 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 12 Month Maintenance of PnOIT | Incidence of All Serious Adverse Events During the Study | 0 SAEs per 100 OIT doses taken |
| 24 Month Maintenance of PnOIT | Incidence of All Serious Adverse Events During the Study | 0 SAEs per 100 OIT doses taken |
Secondary
Incidence of Side Effects During Initial Escalation and Build up Phase of Peanut Oral Immunotherapy
The primary safety outcome of the study is to determine the frequency of side effects during oral immunotherapy in order to assess whether the addition of anti-IgE therapy using Xolair to peanut oral immunotherapy can reduce the number of allergic symptoms that occur during oral immunotherapy when compared to previously published results
Time frame: approximately 24 or 36 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 12 Month Maintenance of PnOIT | Incidence of Side Effects During Initial Escalation and Build up Phase of Peanut Oral Immunotherapy | 2.8 side effects reported per 100 OIT doses |
| 24 Month Maintenance of PnOIT | Incidence of Side Effects During Initial Escalation and Build up Phase of Peanut Oral Immunotherapy | 3.0 side effects reported per 100 OIT doses |
Secondary
The Percentage of Subjects Who Pass the 20gm Peanut Flour (~50% Peanut Protein) Oral Food Challenge Following the Desensitization Phase of the Study
A secondary efficacy outcome of the study is to evaluate whether the addition of anti-IgE therapy using Xolair to peanut oral immunotherapy is able to induce clinical desensitization as measured by passing an oral food challenge to 20 grams of peanut flour on the final day of peanut OIT dosing.
Time frame: approximately 24 or 36 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 12 Month Maintenance of PnOIT | The Percentage of Subjects Who Pass the 20gm Peanut Flour (~50% Peanut Protein) Oral Food Challenge Following the Desensitization Phase of the Study | 4 Participants |
| 24 Month Maintenance of PnOIT | The Percentage of Subjects Who Pass the 20gm Peanut Flour (~50% Peanut Protein) Oral Food Challenge Following the Desensitization Phase of the Study | 2 Participants |
Secondary
The Percentage of Subjects Who Tolerate the Initial Desensitization Day(s) to 950mg of Peanut Flour.
A secondary efficacy outcome of the study is to evaluate whether the addition of anti-IgE therapy using Xolair to a peanut oral immunotherapy protocol allows for a higher amount of peanut tolerated after the rush desensitization phase, thereby reducing the duration of buildup phase and achieving maintenance dosing more rapidly
Time frame: 4 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 12 Month Maintenance of PnOIT | The Percentage of Subjects Who Tolerate the Initial Desensitization Day(s) to 950mg of Peanut Flour. | 1 Participants |
| 24 Month Maintenance of PnOIT | The Percentage of Subjects Who Tolerate the Initial Desensitization Day(s) to 950mg of Peanut Flour. | 2 Participants |