Adjuvant Treatment With Abatacept to Promote Remission During Peanut Oral Immunotherapy

Study Overview
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Brief Summary
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This is a phase 2a, multi-center, randomized and double-blind placebo-controlled trial comparing 24 weeks of abatacept versus placebo used as adjuvant to oral immunotherapy to induce remission in adolescents and adults with persistent severe peanut allergy. This is a proof-of-concept trial in which the primary outcome will be the suppression of the initial peanut specific IgE surge during OIT, which is used as a proxy outcome of peanut allergy remission. Adolescents and adults with persistent severe peanut allergy (n=14) will be randomized to either abatacept or placebo at a ratio 1:1 for a total period of 24 weeks. Peanut oral immunotherapy will be initiated the day following the first administration of the investigational product. Sustained tolerance to peanut will be assessed at 36 weeks.

Official Title
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A Double-blind Randomized Controlled Trial of 6-month of Abatacept vs Placebo as Adjuvant to Peanut Oral Immunotherapy to Induce Immunologic Changes in Patients With Severe Persistent Peanut Allergy

Conditions
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Peanut Allergy

Intervention / Treatment
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* Drug: Abatacept
* Drug: Placebo
* Other: Peanut oral immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female subjects 14 to 50 years old at screening visit History of IgE mediated allergy to peanut protein ImmunoCAP IgE level > 50 kU/L for peanut; Total IgE level < 5000 kU/L Willing to comply to all study requirements during participation in the study; Exclusion Criteria: Previous adverse reactions to abatacept; Known hypersensitivity to abatacept or any of its components; Patients at risk of sepsis, such as immunocompromised or HIV positive; Patient undergoing a treatment with any other biologic agent; Uncontrolled asthma; Unstable angina, significant arrhythmia, uncontrolled hypertension, chronic sinusitis, or other chronic or immunological diseases that, in the judgment of the investigator, might interfere with the evaluation, administration of the test drug or pose additional risk to the subject (e.g., gastrointestinal or gastroesophageal disease, chronic infections, scleroderma, hepatic and gallbladder disease, chronic non-allergic pulmonary disease); Current users of oral, intramuscular, or intravenous corticosteroids, tricyclic antidepressants or beta-blocker Concurrent/prior use of immunomodulatory therapy (within 6 months); A diagnosis of eosinophilic esophagitis, eosinophilic colitis, or eosinophilic gastritis; Pregnant or breastfeeding women;

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 50 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: Abatacept<br> | Drug: Abatacept<br>* 24 week treatment of IV abatacept following recommended dosages from the monograph<br>Other: Peanut oral immunotherapy<br>* Peanut oral immunotherapy, following a patient-driven protocol, starting 24 to 72h after the first administration of abatacept or placebo.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 24 week treatment of IV placebo following recommended dosages from the abatacept monograph<br>Other: Peanut oral immunotherapy<br>* Peanut oral immunotherapy, following a patient-driven protocol, starting 24 to 72h after the first administration of abatacept or placebo.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peanut specific/total IgE at week 24 | Relative change in peanut specific/total IgE from baseline to week 24 | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peanut-specific IgG4/IgE ratio at week 24 | Relative change in peanut-specific IgG4/IgE ratio from baseline to week 24 | 24 weeks | 
| Peanut-specific IgG4 at week 24 | Absolute change in peanut-specific IgG4 from baseline to week 24 | 24 weeks | 
| Sustained tolerance | Maximum period of avoidance after which a oral food challenge with 300 mg peanut protein is still tolerated | Assessed between week 36 and week 48 | 
| Food dosing reactions | Mean cumulative function of food dosing allergic reactions | 48 weeks | 
| Desensitization | Highest tolerated dose on an oral food challenge at week 36 | 36 weeks | 
| Desensitization speed | Time from the onset of oral immunotherapy to the maintenance dose of 300mg | 36 weeks | 
| Adverse events | Overall rate of adverse events | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peanut allergy, Abatacept, Oral immunotherapy