Baked Milk Oral Immunotherapy for Cow's Milk Allergy

Study Overview
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Brief Summary
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The purpose of this study is to determine whether baked milk oral immunotherapy is safe in the treatment of cow's milk allergy.

Detailed Description
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This study is designed to assess the safety of baked milk oral immunotherapy among patients who are milk allergic and who do not pass a baked milk challenge.

Official Title
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Phase II Study of Baked Milk Oral Immunotherapy for the Treatment of Cow's Milk Allergy

Conditions
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Cow's Milk Allergy

Intervention / Treatment
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* Drug: Baked non-fat cow's milk powder
* Drug: Placebo: Tapioca Powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who meet all of the following criteria are eligible for enrollment as study participants, including participants who: Are age 3-18 years, either sex, any ethnicity or race Provide signed informed consent by parent or legal guardian and informed assent if applicable Have a history of symptomatic reactivity to cow's milk (i.e. eczema, urticarial, upper or lower respiratory symptoms, gastrointestinal disturbances, rash, oral symptoms) Have a skin prick test positive to milk (diameter of wheal 3 mm ≥ negative control) and serum milk-specific immunoglobulin E (IgE) level >5 kilo Units (kU)/L within the past 6-12 months Have a positive reaction to a cumulative dose of ≤444 mg of baked milk powder in the initial qualifying double blind placebo-controlled food challenge. Use an effective method of contraception by females of childbearing potential to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of their participation in the study. Have self-injectable epinephrine available at all times Exclusion Criteria: Patients who meet any of these criteria are not eligible for enrollment as study participants, including participants who: Have a history of severe anaphylaxis resulting in hypotension, neurological compromise, or mechanical ventilation Have a history of intubation related to asthma Tolerate more than 444 mg of baked milk powder at the initial qualifying double blind placebo controlled food challenge. Allergy to placebo ingredients or reacts to any dose of placebo during the qualifying oral food challenge. Poor control of atopic dermatitis Are unable to tolerate at least 3 mg of baked milk protein on dose escalation day Are pregnant or lactating Have severe asthma defined by 2007 National Heart Lung and Blood Institute (NHLBI) Criteria Steps 5 or 6 Have severe or poorly controlled asthma defined by with any of the following criteria: Forced expiratory volume in 1 second (FEV1) <80% of predicted Inhaled corticosteroid dosing dosing of >500 mcg daily of fluticasone (or equivalent inhaled corticosteroids based on NHLBI dosing chart) or ≥ 1 hospitalization in the past year for asthma or > 1 emergency department visit in the past 6 months for asthma Use of steroid medications (oral steroids, such as prednisone or Medrol, steroid injections, such as Kenalog, or intravenous or oral corticosteroid burst) in the following manners: History of daily oral steroid dosing within 4 weeks prior to baseline visit or for > 1 month during the past year or >2 burst oral steroid courses in the past 6 months. Are unable to discontinue antihistamines for 5 days for long acting and 3 days for short acting prior to skin testing or food challenges Are receiving omalizumab, mepolizumab, beta- blocker, angiotensin-converting-enzyme inhibitor (ACE-I), angiotensin-receptor blockers, calcium channel blockers, or tricyclic antidepressant therapy Have used immunomodulatory therapy (not including corticosteroids) or biologic therapy within the past year Have participated in any interventional study for treatment of a food allergy in the past 6 months Are on 'build up phase' of environmental allergen immunotherapy. Subjects tolerating maintenance allergen immunotherapy can be enrolled. Have a history of eosinophilic esophagitis in the past 3 years Have a chronic disease (other than asthma, atopic dermatitis, rhinitis) requiring therapy (e.g., heart disease, diabetes) Have used an investigational drug within 90 days or plan to use an investigational drug during the study period Severe reaction at initial double blind placebo controlled food challenge, defined as: Life-threatening anaphylaxis Requiring overnight hospitalization

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 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: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Baked Milk Immunotherapy<br>Subjects will receive baked milk oral immunotherapy with baked non-fat cow's milk powder as the intervention. Subjects will undergo an initial dose escalation, build-up, and then a maintenance period. | Drug: Baked non-fat cow's milk powder<br>* Oral immunotherapy with increasing quantities of baked milk.<br>* Other names: Investigational New Drug (IND) 17114;|
| Placebo Comparator: Placebo<br>Subjects will receive oral immunotherapy with the placebo control (tapioca powder). Subjects will undergo an initial dose escalation, build-up, and then a maintenance period. | Drug: Placebo: Tapioca Powder<br>* Placebo control.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Adverse events will be recorded per CTCAE version 4.0. Events per dose on baked milk oral immunotherapy will be compared to adverse events per dose on placebo. Data will be collected over the first year of treatment. Analysis of cumulative adverse reactions per dose of oral immunotherapy or placebo will be performed at the end of year 1. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Who Are Able to Tolerate 4 Grams of Baked Milk Protein After One Year of Treatment | The investigators will perform baked milk challenges to 4044 mg of baked milk protein and calculate the proportion of subjects who tolerate 4 grams of baked milk protein after one year of baked milk oral immunotherapy. This measure reports the number of participants that were able to tolerate 4 grams of baked milk protein. | 1 year | 
| Proportion of Subjects Who Are Able to Tolerate 2 Grams of Unheated Milk Protein After 2 Years of Treatment | The investigators will perform unheated milk challenges to up to 8000 mg of unheated milk protein and calculate the proportion of subjects who tolerate 2 grams of unheated milk protein after 2 years of treatment. This measure reports the number of participants that were able to tolerate 2 grams of unheated milk protein. | 2 years | 
| Change in Maximum Tolerated Dose of Baked Milk | Change in maximum tolerated dose (milligrams) of baked milk from baseline to end of year 1 and end of year 2. | Baseline, 1 year and 2 years | 
| Change in Milk-specific IgE Level | Change in milk-specific immunoglobulin E (IgE) level measured in kU/L. | Baseline and up to year 4 | 
| Change in Milk-specific IgG4 Level | Change in milk-specific immunoglobulin G4 (IgG4) level measured in mg/L. | Baseline and up to year 4 | 
| Change in Milk Skin Prick Test Responses | Change in milk skin prick test responses measured as a change in wheal size in millimeters. | Baseline and up to year 4 | 
| Change in Quality of Life as Assessed by the Food Allergy Questionnaire | The food allergy questionnaire has an overall score range of 0-6 with 6 indicating the worst quality of life. | Baseline and up to year 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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food allergy, oral immunotherapy