Peanut Epicutaneous Phase II Immunotherapy Clinical Trial

Study Overview
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Brief Summary
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Food allergy occurs when the immune system reacts against foods. The immune system is the part of the body that protects us from illness and germs, but it can also cause allergies. Peanut allergy occurs in 1 - 2% of people in the United States and other Western countries. There is proof that allergy to peanut is increasing. Allergic reactions to peanut can be severe and life threatening. The only way that you can prevent an allergic reaction is to avoid exposure to peanuts. However, peanut proteins are found in a variety of foods and people can be accidently exposed to peanut proteins. Treatment for accidental exposure include antihistamines (medications like Benadryl), and injectable epinephrine (adrenalin) which must be carried at all times. DBV Technologies has developed an epicutaneous delivery system, a patch that puts the peanut protein on the skin.

Detailed Description
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This study will evaluate whether peanut epicutaneous immunotherapy can protect individuals who are allergic to peanuts from having severe allergic reactions, when accidentally exposed to peanuts. The study also looks at the safety of the treatment and the effects it has on the immune system.

Official Title
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Epicutaneous Immunotherapy (EPIT) for Peanut Allergy: A Randomized, Double-Blind, Placebo-Controlled, Phase II Study in Children and Adults (DAIT COFAR6)

Conditions
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Peanut Hypersensitivity, Food Hypersensitivity, Hypersensitivity, Hypersensitivity, Immediate

Intervention / Treatment
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* Biological: Placebo Viaskin® Patch
* Biological: Low-dose DBV712 Viaskin® Patch
* Biological: High-dose DBV712 Viaskin® Patch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Physician-diagnosed peanut allergy OR convincing history of peanut allergy A skin prick test positive to peanut (wheal diameter ≥3mm greater than the saline control) OR detectable peanut specific Immunoglobulin E (IgE) (ImmunoCAP >0.35 kUA/L) Positive reaction to a cumulative dose of ≤1044 mg peanut protein in the initial qualifying Oral Food Challenge (OFC) Use of 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 Ability to perform spirometry maneuvers in accordance with the American Thoracic Society (ATS) guidelines (1994). Children ages 4-11 years who have documented inability to adequately perform spirometry may be enrolled if Peak Expiratory Flow (PEF) is >80% of predicted Provide signed informed consent or assent where indicated Exclusion Criteria: History of anaphylaxis to peanut resulting in hypotension, neurological compromise or requiring mechanical ventilation Participation in a study using an investigational new drug in the last 30 days Participation in any interventional study for the treatment of food allergy in the past 6 months Pregnancy or lactation Current or known allergy to the Viaskin Peanut/Placebo patch device or excipients Current or known allergy to the placebo allergen (oat flour) in oral food challenge (OFC) Currently in a build-up phase of any allergen immunotherapy Severe or poorly controlled atopic dermatitis or greater than a mild flare of active disease at enrollment Forced Expiratory Volume in 1 Second (FEV1) value <80% predicted or any clinical features of moderate or severe persistent asthma baseline severity (as defined by the 2007 NHLBI Guidelines) and greater than high daily doses of inhaled corticosteroids (>500mcg of Fluticasone or equivalent) Use of steroid medications in the following manners: history of daily oral steroid dosing for >1 month during the past year, or burst or steroid course in the past 3 months, or >1 burst oral steroid course in the past year or use of oral or parenteral steroids for a non-asthma indication within the past 30 days Asthma requiring >1 hospitalization in the past year for asthma or >1 Emergency Department (ED) visit in the past 6 months for asthma Any previous intubation/mechanical ventilation due to allergies or asthma Use of omalizumab or other non-traditional forms of allergen immunotherapy or immunomodulatory or biologic therapy in the past year Use of beta-adrenergic blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, or calcium channel blockers in the past 30 days Inability to discontinue antihistamines for skin testing and OFC History of alcohol or drug abuse History of cardiovascular disease, uncontrolled hypertension, arrhythmias, chronic lung disease, active eosinophilic gastrointestinal disease, or other medical conditions including immunologic disorders or HIV infection which, in the opinion of the investigator, make the subject unsuitable for treatment or at increased risk of anaphylaxis or poor outcome

Ages Eligible for Study
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Minimum Age: 4 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo Patch<br>Subjects apply placebo Viaskin® patch daily for a 52-week blinded period. Patch application duration is initially 3 hours and gradually increased to 24 hours over a 21-day graduated dosing period; subsequently patch changed every 24 hours. At Week 52, subjects complete an oral food challenge (OFC) and are unblinded. Following blinded phase, subjects who have not demonstrated sustained unresponsiveness at the Week 52 OFC crossover to active treatment (using the same 21-day graduated dosing period used in the blinded phase) and dose with a high-dose DBV712 Viaskin® patch containing 250 μg peanut protein for a total active treatment period of 30 months (130 weeks). | Biological: Placebo Viaskin® Patch<br>* Placebo (e.g., no peanut) patch in an epicutaneous application for 24 hours every 24 hours.<br>|
| Experimental: 100 µg Peanut Patch<br>Subjects apply low-dose DBV712 Viaskin® patch containing 100 micrograms (μg) peanut protein daily for a 52-week blinded period. Patch application duration is initially 3 hours and gradually increased to 24 hours over a 21-day graduated dosing period; subsequently patch changed every 24 hours. At Week 52, subjects complete an OFC and are unblinded. Following blinded phase, subjects who have not demonstrated sustained unresponsiveness at the Week 52 OFC crossover to active treatment (using same 21-day graduated dosing period used in blinded phase for subjects 4-<6 years old at enrollment or who had Grade 2 reaction or higher within previous 2 months) and dose with a high-dose DBV712 Viaskin® patch containing 250 μg peanut protein for a total active treatment period of 30 months (130 weeks). | Biological: Low-dose DBV712 Viaskin® Patch<br>* 100 microgram (µg) dose of peanut proteins in an epicutaneous application for 24 hours every 24 hours.<br>|
| Experimental: 250 µg Peanut Patch<br>Subjects apply high-dose DBV712 Viaskin® patch containing 250 micrograms (μg) peanut protein daily for a 52-week blinded period. Patch application duration is initially 3 hours and gradually increased to 24 hours over a 21-day graduated dosing period; subsequently patch changed every 24 hours. At Week 52, subjects complete an OFC and are unblinded. Following blinded phase, subjects who have not demonstrated sustained unresponsiveness at the Week 52 OFC continue active treatment with a high-dose DBV712 Viaskin® patch for a total active treatment period of 30 months (130 weeks). | Biological: High-dose DBV712 Viaskin® Patch<br>* 250 microgram (µg) dose of peanut proteins in an epicutaneous application for 24 hours every 24 hours.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With a Successful Treatment Response | Treatment response is defined as a subject who can either (a) successfully consume a cumulative dose of peanut protein equal to or greater than 5044 mg or (b) successfully consume at least a 10-fold increase in peanut protein at the Week 52 oral food challenge (OFC), when compared to the cumulative successfully consumed dose at the baseline OFC. | Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Desensitized to Peanut Protein | Desensitization is defined based on successfully consumed dose in mg protein at the Week 130 oral food challenge (OFC) as follows: 1) 0-44 mg at BL, >=444 mg at Wk 130 2) >44-<444 mg at BL, 10-fold increase at Wk 130 3) >=444 mg at BL, >=5,044 mg at Wk 130. BL=Baseline, Wk 130=Week 130 (Month 30) | Week 130 (Month 30) | 
| Percentage of Subjects Who Can Successfully Consume 1044 mg or 5044 mg Peanut Protein | Subjects who successfully consumed without dose-limiting symptoms 1044 mg or 5044 mg peanut protein during the Week 130 oral food challenge (OFC). This is referred to as the successfully consumed dose (SCD). The maximum SCD for this OFC was 5044 mg peanut protein. | Week 130 (Month 30) | 
| Percentage of Desensitized Subjects in the Active Treatment Arms as Measured by 5044 mg Peanut Protein Oral Food Challenge (OFC) | Desensitization is defined based on successfully consumed dose in mg protein at the Week 52 oral food challenge (OFC) as follows: 0-44 mg at BL, >=444 mg at Wk52 2) >44-<444 mg at BL, 10-fold increase at Wk 52 3) >=444 mg at BL, >=5,044 mg at Wk 52. BL=Baseline, Wk 52=Week 52 | Week 52 | 
| Average Successfully Consumed Dose as Measured by 5044 mg Peanut Protein Oral Food Challenge (OFC) | The successfully consumed dose (SCD) is the cumulative dose consumed during an oral food challenge without dose-limiting symptoms that led to the termination of the challenge. | Week 52 | 
| Percentage of Subjects Who Pass an OFC to 5044 mg of Peanut Protein Followed by an Open Feeding of Peanut Butter After 8 Weeks or 20 Weeks of Discontinuation of Dosing Subsequent to Passing the Week 130 Oral Food Challenge (OFC) | Subjects who after passing the Week 130 (Month 30) discontinue dosing for 8 weeks and later 20 weeks successfully consumed 5044 mg peanut protein during an OFC followed by an open feeding of peanut butter. | 8 and 20 weeks after the Week 130 (Month 30) OFC | 
| Percentage of Subjects With Adverse Events Related to Therapy Through Week 52 and Through 30 Months | Adverse events (AEs) related to study therapy includes both unsolicited AEs where there was a reasonable possibility that the study product caused the event as well as solicited AEs related to dosing. | Week 52 and Month 30 (Week 130) | 
| Percentage of Subjects Who Successfully Complete the Dosing Regimen With no More Than Mild Symptoms Related to Peanut Patch Dosing After 30 Months of Therapy | Mild symptoms related to peanut patch dosing are defined as patch site reactions up to Grade 2 in severity or mild systemic dosing symptoms. | Month 30 (Week 130) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peanut Allergy, Food Allergy, Viaskin peanut patch, Allergen Immunotherapy, Epicutaneous Immunotherapy, Whole peanut extract, Allergenic product, Immediate hypersensitivity