Peanut Oral Immunotherapy and Anti-Immunoglobulin E (IgE) for Peanut Allergy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Peanut OIT & Anti-IgE: Peanut Oral Immunotherapy and Anti-IgE Treatment for Peanut Allergy {NIH R21 Combined Peanut Oral Immunotherapy and Anti-IgE: Mechanistic Studies}

Conditions
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Peanut Hypersensitivity

Intervention / Treatment
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* Drug: Peanut Oral Immunotherapy
* Drug: Omalizumab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 12 month maintenance of PnOIT<br>Randomized subjects who will stay on the maintenance dose of oral peanut immunotherapy (PnOIT) for 12 months. The study has 4 phases: anti-IgE therapy before immunotherapy (Omalizumab), an initial desensitization day(s), a buildup period, and a daily home maintenance phase with a final dose of 8000mg peanut flour ( 50% peanut protein). Then all subjects will be randomized to an additional 1 or 2 years (12 or 24 months) of maintenance OIT. An OFC will be performed at the end of the long-term maintenance in all groups. | Drug: Peanut Oral Immunotherapy<br>* 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.<br>* Other names: PnOIT;Drug: Omalizumab<br>* 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.<br>* Other names: Xolair;|
| Active Comparator: 24 month maintenance of PnOIT<br>All subjects will be on the same intervention until Randomization. Randomized subjects who will stay on the maintenance dose of peanut oral immunotherapy (PnOIT) for 24 months. The study has 4 phases: anti-IgE therapy before immunotherapy (Omalizumab), an initial desensitization day(s), a buildup period, and a daily home maintenance phase with a final dose of 8000mg peanut flour ( 50% peanut protein). Then all subjects will be randomized to an additional 1 or 2 years (12 or 24 months) of maintenance OIT. An OFC will be performed at the end of the long-term maintenance in all groups. | Drug: Peanut Oral Immunotherapy<br>* 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.<br>* Other names: PnOIT;Drug: Omalizumab<br>* 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.<br>* Other names: Xolair;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | approximately 24 or 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 4 months | 
| 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. | approximately 24 or 36 months | 
| 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 | approximately 24 or 36 months | 
| 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 | approximately 24 or 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peanut, Allergy, Hypersensitivity