Omalizumab to Accelerate a Symptom-driven Multi-food OIT

Study Overview
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Brief Summary
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This study will determine the dose-related efficacy of a 20-week treatment of omalizumab started 8 weeks before the onset of a symptom-driven multi-food oral immunotherapy (OIT) protocol at decreasing time to OIT maintenance dose. Two dosages of omalizumab will be compared to placebo during an oral immunotherapy protocol for three simultaneous food allergens.

Detailed Description
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This is a phase 2b, multi-center randomized controlled trial comparing 2 doses of omalizumab to placebo in subjects 6 to 25 years old with multiple food allergies undergoing a symptom-driven multi-food OIT protocol. Subjects will undergo a screening period involving a DBPCFC to a mix of three allergens which will determine their eligibility and eliciting dose. Eligible subjects will be randomized to one of 2 omalizumab dosages or placebo at a ratio of 2:2:1 for a total period of 20 weeks. They will undergo initial food escalation (IFE) to determine their starting food treatment mix dose for three simultaneous food allergens after a pre-treatment period of 8 weeks with the study drug. Subjects will undergo up-dosing OIT visits at the clinic every two weeks, until a maintenance dose of 1500mg of protein (500mg per food) is reached (primary endpoint).

Official Title
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A 15 Months, Double-Blind, Randomized Controlled Trial Comparing 20 Weeks of Two Dosages of Omalizumab to Placebo to Accelerate a Symptom-driven Oral Immunotherapy Schedule in Subjects Aged 6 to 25 Years With Multiple Food Allergies

Conditions
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Omalizumab, Food IgE-mediated Allergy, Immunotherapy, Physiological Effects of Drugs

Intervention / Treatment
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* Biological: Omalizumab 16mg/kg
* Biological: Omalizumab 8mg/kg
* Biological: Placebo
* Other: Multi-food oral immunotherapy (OIT)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male or female subjects 6 to 25 years old at screening visit. History of IgE-mediated allergy to at least three foods within the following list: peanut, milk, egg, wheat, oat, soy, barley, rye, buckwheat, hazelnut, pecan, cashew, pistachio, almond, walnut and sesame. Subjects currently following a strict avoidance of these three foods. Positive SPT with a largest wheal diameter ≥ 6 mm to all three foods. Food-specific IgE level greater than 15 kU/L for all three foods Positive DBPCFC to treatment food mix with an eliciting dose ≤ 300 mg of total food protein. Signed informed consent and assent. Exclusion criteria Subjects reacting objectively to the placebo during the screening DBPCFC. Severe asthma as defined by GINA 201948. Active or past confirmed eosinophilic oesophagitis. Subject currently under allergen immunotherapy. Subject/parent with excessive anxiety unlikely to cope with study conditions as per investigator's opinion. Subject/parent unwillingness to comply with study requirements. Subject unwillingness to ingest a daily food dose of up to 1500 mg of allergen protein. Inability to discontinue anti-histamine medication prior to study procedures. Known allergy to omalizumab or its excipients. Known allergy to components of the placebo food treatment mix that cannot be substituted without interfering with the blind (e.g.: dates, banana, chocolate syrup) Use of immunosuppression or immunomodulatory drug (including omalizumab) or food oral immunotherapy or investigational treatment or procedure within 1 year. Relative contraindication or inability to use epinephrine auto-injector. Subjects receiving beta-blockers or angiotensin converting-enzyme (ACE) inhibitors. Pregnancy or lactation for the duration of the study. Any condition that is not compatible with the study treatment or procedures as per investigator judgment.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 25 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: Omalizumab 16 mg/kg<br>Participants will receive omalizumab 16 mg/kg monthly doses for 12 weeks, followed by omalizumab 8 mg/kg monthly for 4 weeks and then omalizumab 4 mg/kg monthly for 4 weeks. Multi-food oral immunotherapy following a symptom-driven schedule will begin 8 weeks after starting study drug. | Biological: Omalizumab 16mg/kg<br>* Participants will receive omalizumab 16 mg/kg monthly doses for 12 weeks, followed by omalizumab 8 mg/kg monthly for 4 weeks and then omalizumab 4 mg/kg monthly for 4 weeks, for a total of 20 weeks including a taper period.<br>Other: Multi-food oral immunotherapy (OIT)<br>* Multi-food oral immunotherapy will be conducted to a mix of three foods. It will be started 8 weeks after study drug with an initial food escalation. Participants will undergo biweekly increase until they tolerate a maintenance dose of 1500 mg (500 mg per food) of food protein.<br>|
| Experimental: Omalizumab 8 mg/kg<br>Participants will receive omalizumab 8 mg/kg monthly doses for 12 weeks, followed by omalizumab 4 mg/kg monthly for 4 weeks and then omalizumab 2 mg/kg monthly for 4 weeks. Multi-food oral immunotherapy following a symptom-driven schedule will begin 8 weeks after starting study drug. | Biological: Omalizumab 8mg/kg<br>* Participants will receive omalizumab 8 mg/kg monthly doses for 12 weeks, followed by omalizumab 4 mg/kg monthly for 4 weeks and then omalizumab 2 mg/kg monthly for 4 weeks, for a total of 20 weeks including a taper period.<br>Other: Multi-food oral immunotherapy (OIT)<br>* Multi-food oral immunotherapy will be conducted to a mix of three foods. It will be started 8 weeks after study drug with an initial food escalation. Participants will undergo biweekly increase until they tolerate a maintenance dose of 1500 mg (500 mg per food) of food protein.<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo doses for 20 weeks. The doses will be injected every 2 or 4 weeks depending on the weight of the participant. Multi-food oral immunotherapy following a symptom-driven schedule will begin 8 weeks after starting study drug. | Biological: Placebo<br>* Participants will receive placebo for 8 weeks prior to the initiation of oral immunotherapy and 12 weeks after for a total of 20 weeks including a taper period.<br>Other: Multi-food oral immunotherapy (OIT)<br>* Multi-food oral immunotherapy will be conducted to a mix of three foods. It will be started 8 weeks after study drug with an initial food escalation. Participants will undergo biweekly increase until they tolerate a maintenance dose of 1500 mg (500 mg per food) of food protein.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the efficacy of omalizumab at decreasing time-to-maintenance during a symptom-driven multi-food OIT protocol. | Time from IFE to target multi-food protein maintenance dose of 1500 mg of total food protein | Assessed up to 52 weeks after IFE | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in reactivity threshold to food treatment mix after pre-treatment with study drug. | Measured as the amount of food allergen eliciting an objective allergic reaction on double-blinded oral food challenge or initial food escalation. | Measured 8 weeks after starting investigational product | 
| Average up-dosing speed while on study drug. | Average of (log of escalation %)/(days since last escalation) for all escalation visits while on study drug | From week 0 to week 12 post IFE | 
| Mean cumulative function of allergic adverse events attributable to food dosing throughout the trial. | AEs will be captured using the daily dosing diary throughout the trial, including during maintenance. Any systemic reaction having occurred since the last visit will be reviewed and graded by the investigator according to the CoFAR grading system. | For one year following IFE | 
| Rate of treatment failure | Subject which stop daily ingestion of food treatment mix, prior to achieving study maintenance dose, for a period of 14 days or more | At any time during the 12-month OIT phase | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multi-food OIT, oral immunotherapy, omalizumab, symptom-driven protocol, double-Blind, randomized controlled trial