Efficacy and Safety of Several Doses of Viaskin Peanut in Adults and Children With Peanut Allergy

Study Overview
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Brief Summary
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The objectives of this dose-finding study for the treatment of peanut allergy are: To determine the efficacy of 3 doses of Viaskin Peanut (50 mcg ,100 mcg and 250 mcg peanut protein per patch) to significantly desensitize peanut-allergic subjects to peanut after 12 months of treatment. To evaluate the safety of a long-term treatment with Viaskin Peanut.

Detailed Description
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Peanut allergy is a common allergy in the United States, with a prevalence in the general population as high as 1%. Peanut allergy management is based on strict peanut avoidance and injectable epinephrine after the allergic systemic reactions have started. Specific Immunotherapy methods currently available have shown some limitations in their use because of safety issues. Hence, there is an important unmet medical need for efficient and safe treatment of peanut allergy. DBV Technologies has developed an epicutaneous delivery system, called Viaskin, a method based on delivering precise quantity of the allergen on the upper layers of the skin. Avoiding contact between the allergen and the bloodstream should confer to epicutaneous immunotherapy (EPIT) a higher level of safety as systemic reactions should be circumvented The VIPES study is a 12-month double-blind, placebo-controlled,randomized trial to study the efficacy and safety of Viaskin Peanut in subjects from 6 to 55 years old with a history of immediate hypersensitive reaction to peanut protein. The trial will be conducted at sites with investigators and staff trained and experienced in the diagnosis and the management of peanut allergy and anaphylaxis, and who are capable of performing a double-blind placebo-controlled food challenge (DBPCFC) in adult and/or pediatric subjects. Three doses of peanut proteins, i.e. 50 mcg, 100 mcg and 250 mcg will be evaluated for the study. Following the confirmation of peanut allergy at screening, subjects will be randomized in a 1:1:1:1 ratio into four different treatment groups, including 50 mcg, 100 mcg and 250 mcg peanut protein or placebo. Treatment will be comprised of daily applications of Viaskin Peanut or placebo patch for 12 months. Each subject will undergo two DBPCFCs: one at screening and one at Month 12. A follow up visit will be performed 2 weeks after completion of treatment and the last DBPCFC.

Official Title
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A Double-blind, Placebo-controlled, Randomized Trial to Study the Viaskin Peanut's Efficacy and Safety for Treating Peanut Allergy in Children and Adults.

Conditions
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Peanut Allergy

Intervention / Treatment
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* Biological: Viaskin Peanut 50 mcg
* Biological: Viaskin Peanut 100 mcg
* Biological: Viaskin Peanut 250 mcg
* Biological: Viaskin Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Peanut-allergic subjects between 6 and 55 years of age, with a well-documented medical history of systemic reactions after ingestion of peanut and currently following a strict peanut-free diet. Peanut-specific immunoglobulin E (IgE) level (Phadia CAP-system) > 0.7 kU/L and a positive skin prick test to peanut with a largest wheal diameter ≥ 8 mm Positive double-blind placebo-controlled food challenge (DBPCFC) at ≤ 300 mg of peanut proteins: the eliciting dose of peanut proteins during the DBPCFC is capped at 300 mg, i.e. subjects must react to peanut before reaching or at the dose of 300 mg peanut proteins. Negative pregnancy test for women of childbearing potential. Females of childbearing age must use effective methods of contraception to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of participation in the study. Sexual abstinence will be accepted as an effective method of contraception for girls below 15 years of age. Ability to perform spirometry maneuvers in accordance with the American Thoracic Society guidelines (2005) for subjects 9 years of age and above Subjects below 9 years of age can perform peak expiratory flow (PEF) instead. Willing to comply with all study requirements during their participation in the study. Provide signed informed consent and assent as appropriate. Exclusion Criteria: Subjects with a history of severe anaphylaxis to peanut with the following symptoms: hypotension, hypoxia, neurological compromise (collapse, loss of consciousness or incontinence). Pregnancy or lactation. FEV1 <80% of the predicted value at screening for subjects 9 years of age and above. PEF < 80% of predicted for subjects below 9 years of age. Subjects who did not react at or below the dose of 300 mg of peanut proteins during the DBPCFC at screening. Known allergy or known hypersensitivity to placebo excipients either of the Viaskin patches or of the food challenge formulas. Subjects reacting objectively to the placebo formula at screening. Severe reaction during the screening food challenge, defined as need for intubation, hypotension persisting after epinephrine administration, or the need for more than two doses of epinephrine. Inability to discontinue short-acting antihistamines for three days or long-acting antihistamines for five to seven days (depending on half-life) prior to skin prick testing or food challenges. Subjects treated with systemic long-acting corticosteroids (depot corticosteroids) within 12 weeks prior to the screening visit and/or systemic short-acting corticosteroid within 4 weeks prior to the screening visit or any systemic corticosteroid at screening. Subjects with asthma defined as follows: uncontrolled persistent asthma by National Asthma Education and Prevention Program Asthma guidelines (2007) or by Global Initiative for Asthma (2011) or being treated with combination therapy of medium dose inhaled corticosteroid with a long acting inhaled β2-agonists; at least two systemic corticosteroid courses for asthma in the past year or one oral corticosteroid course for asthma in the past three months; prior intubation for asthma in the past two years. Subjects on β-blocking agents, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant therapy. Subjects undergoing any type of immunotherapy to any food within one year prior to the screening visit. Subjects presently on aeroallergen immunotherapy and unwilling or unable to discontinue. Subjects currently treated with anti-tumor necrosis factor drugs or anti-IgE drugs (such as omalizumab) or any biologic immunomodulatory therapy within one year prior to the screening visit. Allergy or known history of reaction to Tegaderm®. Subjects suffering from generalized dermatologic diseases (e.g. severe atopic dermatitis, uncontrolled generalized eczema, keratosis pilaris, ichthyosis vulgaris) with no intact skin zones to apply the patches. Any disorder in which epinephrine is contraindicated such as coronary artery disease, uncontrolled hypertension, or serious ventricular arrhythmias. Participation in another clinical intervention study in the three months prior to the screening visit. Subjects on any experimental drugs or treatments. Other inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 55 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: Viaskin Peanut 50 mcg<br> | Biological: Viaskin Peanut 50 mcg<br>* Subjects epicutaneously administered for 24 hours every 24 hours with a patch containing 50 mcg peanut proteins as whole peanut extract<br>|
| Experimental: Viaskin Peanut 100 mcg<br> | Biological: Viaskin Peanut 100 mcg<br>* Subjects epicutaneously administered for 24 hours every 24 hours with a patch containing 100 mcg peanut proteins as whole peanut extract<br>|
| Experimental: Viaskin Peanut 250 mcg<br> | Biological: Viaskin Peanut 250 mcg<br>* Subjects epicutaneously administered for 24 hours every 24 hours with a patch containing 250 mcg peanut proteins as whole peanut extract<br>|
| Placebo Comparator: Viaskin Placebo<br> | Biological: Viaskin Placebo<br>* Subjects epicutaneously administered for 24 hours every 24 hours with a patch containing a matching placebo formulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Treatment Responders at Month 12; Analyzed in Overall Population | A treatment responder was defined as a participant with a peanut protein eliciting dose equal to or greater than 1,000 mg peanut proteins based on the results of the DBPCFC after 12 months of treatment or a participant with a >=10-fold increase of the eliciting dose at 12 months, compared to the initial eliciting dose. For participants with missing treatment response at Month 12, last observation carried forward (LOCF) imputation was used (i.e., participants were considered as non-responders). | At Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Treatment Responders at Month 12; Analyzed in Children (6-11 Years of Age) | A treatment responder was defined as a participant with a peanut protein eliciting dose equal to or greater than 1,000 mg peanut proteins based on the results of the DBPCFC after 12 months of treatment or a participant with a >=10-fold increase of the eliciting dose at 12 months, compared to the initial eliciting dose. For participants with missing treatment response at Month 12, LOCF imputation was used (i.e., participants were considered as non-responders). | At Month 12 | 
| Percentage of Treatment Responders at Month 12; Analyzed in Adolescents (12-17 Years of Age) | A treatment responder was defined as a participant with a peanut protein eliciting dose equal to or greater than 1,000 mg peanut proteins based on the results of the DBPCFC after 12 months of treatment or a participant with a >=10-fold increase of the eliciting dose at 12 months, compared to the initial eliciting dose. For participants with missing treatment response at Month 12, LOCF imputation was used (i.e., participants were considered as non-responders). | At Month 12 | 
| Percentage of Treatment Responders at Month 12; Analyzed in Adults (18-55 Years of Age) | A treatment responder was defined as a participant with a peanut protein eliciting dose equal to or greater than 1,000 mg peanut proteins based on the results of the DBPCFC after 12 months of treatment or a participant with a >=10-fold increase of the eliciting dose at 12 months, compared to the initial eliciting dose. For participants with missing treatment response at Month 12, LOCF imputation was used (i.e., participants were considered as non-responders). | At Month 12 | 
| Mean Eliciting Doses of Peanut Proteins at Month 12; Analyzed in Overall Population | The peanut protein eliciting dose was defined as the first dose of peanut protein administered to the participant during the DBPCFC procedure which caused an objective allergic reaction. This was capped to 300 mg at the screening DBPCFC and to 2000 mg at the Month 12 DBPCFC. For participants with missing treatment response at Month 12, LOCF imputation was used (i.e., participants were considered as non-responders). | At Month 12 | 
| Mean Eliciting Doses of Peanut Proteins at Month 12; Analyzed in Children (6-11 Years of Age) | The peanut protein eliciting dose was defined as the first dose of peanut protein administered to the participant during the DBPCFC procedure which caused an objective allergic reaction. This was capped to 300 mg at screening DBPCFC and to 2000 mg at the Month 12 DBPCFC. For participants with missing treatment response at Month 12, LOCF imputation was used (i.e., participants were considered as non-responders). | At Month 12 | 
| Mean Eliciting Doses of Peanut Proteins at Month 12; Analyzed in Adolescents (12-17 Years of Age) | The peanut protein eliciting dose was defined as the first dose of peanut protein administered to the participant during the DBPCFC procedure which caused an objective allergic reaction. This was capped to 300 mg at screening DBPCFC and to 2000 mg at the Month 12 DBPCFC. For participants with missing treatment response at Month 12, LOCF imputation was used (i.e., participants were considered as non-responders). | At Month 12 | 
| Mean Eliciting Doses of Peanut Proteins at Month 12; Analyzed in Adults (18-55 Years of Age) | The peanut protein eliciting dose was defined as the first dose of peanut protein administered to the participant during the DBPCFC procedure which caused an objective allergic reaction. This was capped to 300 mg at screening DBPCFC and to 2000 mg at the Month 12 DBPCFC. For participants with missing treatment response at Month 12, LOCF imputation was used (i.e., participants were considered as non-responders). | At Month 12 | 
| Mean Cumulative Reactive Dose of Peanut Proteins at Month 12; Analyzed in Overall Population | The peanut protein cumulative reactive dose was defined as the sum of all peanut protein doses up to and including the eliciting dose ingested during the peanut challenge. For participants with missing treatment response at Month 12, LOCF imputation was used (i.e., participants were considered as non-responders). | At Month 12 | 
| Change From Baseline in Severity of Symptoms Based on the Oral Food Challenge (OFC) Symptom Score Sheet at Month 12; Analyzed in Overall Population | The symptoms of erythematous rash, pruritus, urticaria/angioedema, rash, sneezing/itching, nasal congestion, rhinorrhea, laryngeal symptoms (example, throat clearing, occasional cough, hoarseness, frequent dry cough, inspiratory stridor), wheezing, subjective complaints, objective complaints and cardiovascular symptoms (example, color change, weakness, dizziness, mental status change, tachycardia, decreased blood pressure, etc) were observed. The OFC score ranges from 0 to 3 for each symptom (0=Absent, 1=mild, 2=moderate or 3=severe). The total symptom score for each participant was calculated. Higher scores indicate worst outcome. For participants with missing treatment response at Month 12, LOCF imputation was used (i.e., participants were considered as non-responders). | Baseline and Month 12 | 
| Number of Participants With an Average Wheal Diameter Ratio ≤0.5 and >0.5 at Each Skin Prick Test Dilution at Months 3, 6 and 12; Analyzed in Overall Population | The mean wheal diameter of skin prick test (sum of the orthogonal diameters divided by 2) at each time point is calculated for the 5 skin prick tests at baseline and at each time point, i.e., Months 3, 6 and 12: undiluted, diluted 1:10 millimeter (mm), diluted 1:100 (mm), diluted 1:1,000 (mm), diluted 1:10,000 (mm). The ratio of the mean wheal diameter at each time point for a specific dilution versus the baseline value for that specific dilution was calculated and classified as <=0.5 or >0.5, allowing to assess the number of participants of those mean wheal diameters that have been at least halved from the baseline value. | Baseline and Months 3, 6 and 12 | 
| Change From Baseline in Peanut-Specific Immunoglobulin E (IgE) at Months 3, 6 and 12; Analyzed in Overall Population | Venous blood samples were taken for assessment of the peanut-specific IgE at 3, 6 and 12 months. Results are presented using multiple imputation to replace missing values. | Baseline and Months 3, 6 and 12 | 
| Change From Baseline in Peanut-Specific IgE at Months 3, 6 and 12; Analyzed in Children (6-11 Years of Age) | Venous blood samples were taken for assessment of the peanut-specific IgE at 3, 6 and 12 months. Results are presented using multiple imputation to replace missing values. | Baseline and Months 3, 6 and 12 | 
| Change From Baseline in Peanut-Specific IgE at Months 3, 6 and 12; Analyzed in Adolescents (12-17 Years of Age) | Venous blood samples were taken for assessment of the peanut-specific IgE at 3, 6 and 12 months. Results are presented using multiple imputation to replace missing values. | Baseline and Months 3, 6 and 12 | 
| Change From Baseline in Peanut-Specific IgE at Months 3, 6 and 12; Analyzed in Adults (18-55 Years of Age) | Venous blood samples were taken for assessment of the peanut-specific IgE at 3, 6 and 12 months. Results are presented using multiple imputation to replace missing values. | Baseline and Months 3, 6 and 12 | 
| Change From Baseline in Peanut-Specific Immunoglobulin G Subtype 4 (IgG4) at Months 3, 6 and 12; Analyzed in Overall Population | Venous blood samples were taken for assessment of the peanut-specific IgG4 at 3, 6 and 12 months. Results are presented using multiple imputation to replace missing values. | Baseline and Months 3, 6 and 12 | 
| Change From Baseline in Peanut-Specific IgG4 at Months 3, 6 and 12; Analyzed in Children (6-11 Years of Age) | Venous blood samples were taken for assessment of the peanut-specific IgG4 at 3, 6 and 12 months. Results are presented using multiple imputation to replace missing values. | Baseline and Months 3, 6 and 12 | 
| Change From Baseline in Peanut-Specific IgG4 at Months 3, 6 and 12; Analyzed in Adolescents (12-17 Years of Age) | Venous blood samples were taken for assessment of the peanut-specific IgG4 at 3, 6 and 12 months. Results are presented using multiple imputation to replace missing values. | Baseline and Months 3, 6 and 12 | 
| Change From Baseline in Peanut-Specific IgG4 at Months 3, 6 and 12; Analyzed in Adults (18-55 Years of Age) | Venous blood samples were taken for assessment of the peanut-specific IgG4 at 3, 6 and 12 months. Results are presented using multiple imputation to replace missing values. | Baseline and Months 3, 6 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food allergy, Immediate hypersensitivity, Whole peanut extract, Allergenic product, Specific Immunotherapy, Epicutaneous Immunotherapy (EPIT)