Oral Immunotherapy for Peanut Allergic Patients

Study Overview
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Brief Summary
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Multicenter, double-blind, randomized, placebo-controlled phase I/II study to determine the safety, tolerability, potential efficacy and dose finding of INP20, an oral immunotherapy in peanut-allergic patients. The overall study design consists of two sequential periods of Part A and Part B. Part A is a dose escalation study in patients from 12 to 65 years old with a history of immediate hypersensitive reaction to peanut protein. Six diferent oral-dose of INP20 will be administered to 6 cohorts of patients once daily for 2 weeks. Part B is a 6-month double-blind, placebo-controlled, randomized and parallel groups study. Patients will be randomized in a 1:1:1 ratio into three (3) different treatment groups, including placebo and the two doses of peanut protein selected from Part A. They will recieve INP20 once daily for 6 months.

Official Title
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A Multicenter Double-blind, Randomized, Placebocontrolled Phase I/II Study to Determine the Safety, Tolerability, Potential Efficacy and Dose Finding of INP20, an Oral Formulation for Treatment of Immunotherapy in Peanut-allergic Patients

Conditions
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Peanut Allergy

Intervention / Treatment
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* Drug: INP20
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The presence of specific IgE to peanuts (a positive skin prick test to peanuts (diameter of wheal > 3.0 mm) and a positive peanut IgEs [CAP-FEIA] > 0.35 kUA/L. A history of significant clinical symptoms occurring within 60 minutes after ingesting peanuts. Have a positive double-blind placebo-controlled food challenge (DBPCFC) to peanut at a cumulative dose of less than 10 grams of peanut protein. Provide signed informed consent for the participation in the study. Have self-injectable epinephrine available at home and be trained on its proper use. Potentially fertile women must agree to be sexually inactive or to use appropriate contraceptive measures for the duration of the study and for 1 month afterward. Exclusion Criteria: History of severe anaphylaxis to peanut as defined by respiratory distress with cyanosis, hypoxemia (O2 Sat <92%) or, in the absence of other clinical records, severe dyspnea; hypotension with or without loss of consciousness; or relaxation of sphincters. Currently participating in another study using an investigational new drug. Participation in any interventional study, specific oral or sublingual immunotherapy building up phase for the treatment of food allergy in the past 12 months. Allergic to placebo ingredients or reacts to any dose of placebo during study entry DBPCFC. Patients allergic to corn food. Poor control or persistent activation of severe atopic dermatitis. Moderate to severe persistent asthma. Prior intubation/mechanical ventilation for asthma. Currently being treated with greater than medium daily doses of inhaled corticosteroids (fluticasone >500 μg per day, ciclesonide >400 μg per day or budesonide >800 μg per day) or montelukast. Chronic gastrointestinal diseases. Primary or secondary immunodeficiency. Have a severe reaction at initial DBPCFC (life-threatening anaphylaxis or reaction requiring hospitalization). Chronic use of beta blockers, angiotensin converting enzyme inhibitors, or monoamine oxidase inhibitors, proton pump inhibitors, H2-bloquers, prokinetic drugs and laxatives. Inability to discontinue antihistamines for 7 days before skin testing and oral food challenges (OFCs). Patients diagnosed with other serious food allergies defined as those who have required intubation and/or ICU admission. Women of childbearing potential (unless they are using highly effective methods of contraception during dosing and for at least 1 month after stopping medication), who are pregnant, planning to become pregnant, or breastfeeding. Past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the participant's ability to comply with study requirements or that may impact the quality or interpretation of the data obtained from the study may also exclude a participant from the study.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 65 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INP20 (Oral Immunotherapy)<br> | Drug: INP20<br>* Part A: Oral INP20 administration at ascending doses once daily for 2 weeks. Part B: Two doses of oral INP20 derived from Part A once daily for 6 months.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Part A: Oral placebo administration onces daily for 2 weeks. Part B: Oral placebo administration onces daily for 6 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate, severity, and relationship to treatment of adverse events (AEs) and serious adverse events (SAEs) | Safety of the investigational product | Week 4 and Week 25 | 
| Number of patients experiencing any dose limiting toxicity (DLT) | Tolerability of the investigational product | Week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Immunoglobulin G subtype (IgG4) and basophil activation on the BAT (basophil activation test). | Pharmacodynamics | Week 4 | 
| Differences in reaction thresholds (challenge test) to peanut of treatment groups versus the placebo after 6 months of INP20 treatment. | Efficacy of the investigational product | Week 24 |