Follow-up of the VIPES Study to Evaluate Efficacy and Safety of Viaskin Peanut in Adults and Children

Study Overview
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Brief Summary
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The objectives of this open-label follow-up study for subjects who previously were randomized and have completed the VIPES study for the treatment of peanut allergy, are: To assess the efficacy of Viaskin Peanut after up to 36 months of treatment. To evaluate the safety of long-term treatment with Viaskin Peanut. To evaluate sustained unresponsiveness to peanut after a period of 2 months without treatment in subjects showing desensitization to peanut after 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 OLFUS-VIPES study is an open-label follow-up study for subjects who previously were randomized and have completed the VIPES efficacy and safety study. Subjects will be offered enrollment in this follow-up study to receive an additional 24 months of Viaskin Peanut treatment followed by a period of 2 months without treatment while maintaining a peanut-free diet. The trial will be conducted at the same sites as the VIPES study 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. According to the current amended study protocol, all subjects enrolling into the OLFUS-VIPES study after having completed the VIPES study will receive the highest dose of Viaskin Peanut, i.e. 250 mcg peanut protein, regardless of prior treatment (placebo, 50 mcg, 100 mcg or 250 mcg Viaskin Peanut) they were receiving in the VIPES study. Subjects who already enrolled into the OLFUS-VIPES study under the initial protocol design will all switch to receive the 250 mcg dose at Month 6 or at Month 12 of treatment in the OLFUS-VIPES study upon approval of the amended protocol at their sites. The study will remain blinded for all subjects until the VIPES study is unblinded. All subjects completing the OLFUS-VIPES study should receive overall 24 months of active treatment followed by a period of 2 months without treatment for those subjects being assessed for sustained unresponsiveness.

Official Title
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Open-label Follow-up Study of the VIPES Study to Evaluate Long-term Efficacy and Safety of the Viaskin Peanut

Conditions
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Peanut Allergy

Intervention / Treatment
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* Biological: Viaskin Peanut 250 mcg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult and pediatric subjects (≥7 years) who completed the VIPES study, with a mandatory and documented DBPCFC at Month 12 in the VIPES study. Signed informed consent from adult subjects or parent(s)/guardian(s) of children <18 years and children's assent for children >7 years or as per country-specific regulations or laws. This consent should be signed no later than Visit 11 in the VIPES study. Negative pregnancy test for women of childbearing potential at Visit 10 in the VIPES study. Female subject of childbearing potential 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. Documented sexual abstinence will be accepted as an effective method of contraception for girls below 15 years of age. Subjects and/or parents/guardians willing to comply with all study requirements during their participation in the study. Exclusion Criteria: Severe reaction during the DBPCFC at Month 12 in the VIPES study, defined as need for intubation, hypotension persisting after epinephrine administration, and/or the need for more than two doses of epinephrine. Pregnancy or lactation. Females of childbearing potential planning a pregnancy in the coming 2 to 3 years. Subjects who became allergic to chocolate or who do not want to consume the chocolate study challenge vehicle anymore. Subjects who developed hypersensitivity to excipients of the Viaskin patches or of the food challenge formula used during the VIPES study. 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 with asthma that has evolved and now fulfills any of the criteria 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 year. Subjects receiving β-blocking agents, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant therapy. Subjects receiving or planning to receive anti-tumor necrosis factor drugs or anti-IgE drugs (such as omalizumab) or any biologic immunomodulatory therapy. Subjects receiving or planning to receive any type of immunotherapy to any food (e.g. oral immunotherapy, sublingual immunotherapy, specific oral tolerance induction) during their participation in the study. Subjects receiving or planning to receive any aeroallergen immunotherapy during their participation in the study. Allergy or known history of reaction to Tegaderm® with no possibilities to use an alternative dressing approved by the sponsor. Subjects suffering from generalized dermatologic disease (e.g. severe atopic dermatitis, uncontrolled generalized eczema, ichthyosis vulgaris) with no intact zones to apply the patches. Any new disorder in which epinephrine is contraindicated such as coronary artery disease, uncontrolled hypertension, or serious ventricular arrhythmias. A history of non compliance in the VIPES study. Non compliance is defined as subjects not applying the patch at all for 60 days or more (this can be either consecutive or intermittent non-application of the patches) during the whole VIPES study duration Participation in another clinical intervention study in the past year, other than the VIPES study. Subjects on any experimental drugs in the past year, other than those used in the VIPES study. Other inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 56 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 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>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Treatment Responders at Months 12 and 24 | A treatment responder was defined as a participant with a peanut protein eliciting dose (ED) equal to or greater than 1000 milligram (mg) peanut protein or with at least a 10-fold increase of the ED compared to their initial ED observed at the VIPES baseline, as determined by double-blind placebo-controlled food challenge (DBPCFC) at Months 12 and 24. At Month 12, participants had received 24 months of active treatment for those who received Viaskin Peanut in the VIPES study, and 12 months of active treatment for those who received placebo in the VIPES study. At Month 24, participants had received 36 months of active treatment for those who received Viaskin Peanut in the VIPES study, and 24 months of active treatment for those who received placebo in the VIPES study. The percentage of responders at Month 12 and Month 24 are presented according to whether participants received Viaskin Peanut or placebo during the VIPES study. | Month 12 and Month 24 (end of treatment) of the OLFUS-VIPES study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Unresponsive to a Cumulative Dose of at Least 1440 mg Peanut Protein at Month 24 | Participants were considered unresponsive if they showed no objective symptoms leading to stopping the challenge during the Month 24 DBPCFC with a cumulative dose of at least 1440 mg of peanut protein, up to a cumulative dose of 5044 mg peanut protein. The percentage of unresponsive participants is presented according to whether participants received Viaskin Peanut or placebo during the VIPES study. | Month 24 (end of treatment) of the OLFUS-VIPES study | 
| Percentage of Participants With a Sustained Unresponsiveness to a Cumulative Dose of at Least 1440 mg Peanut Protein at Month 26 | Participants who were unresponsive to a cumulative dose of 1440 mg of peanut protein or above at the Month 24 DBPCFC, had an additional 2-month period without treatment and continued on a peanut-free diet to assess for sustained unresponsiveness by a DBPCFC at Month 26. The percentage of participants with this sustained unresponsiveness, i.e, who showed no objective symptoms leading to stopping the challenge during the DBPCFC to a cumulative dose of 1440 mg of peanut protein or above at Month 26, are presented according to whether participants received Viaskin Peanut or placebo during the VIPES study. | Month 26 (2 months post-treatment) of the OLFUS-VIPES study | 
| Median Cumulative Reactive Dose of Peanut Protein at Months 12 and 24 | The cumulative reactive dose was defined as the sum of all peanut protein doses taken by the participant during the DBPCFC. To distinguish participants who reached the highest dose of the DBPCFC without objective symptoms 1000 mg was added to the cumulative reactive dose to obtain an adjusted value. The median cumulative reactive doses at Months 12 and 24 are presented according to whether participants received Viaskin Peanut or placebo during the VIPES study. | Month 12 and Month 24 (end of treatment) of the OLFUS-VIPES study | 
| Mean Cumulative Reactive Dose of Peanut Protein at Months 12 and 24 | The cumulative reactive dose was defined as the sum of all peanut protein doses taken by the participant during the DBPCFC. To distinguish participants who reached the highest dose of the DBPCFC without objective symptoms 1000 mg was added to the cumulative reactive dose to obtain an adjusted value. The mean cumulative reactive doses at Months 12 and 24 are presented according to whether participants received Viaskin Peanut or placebo during the VIPES study. | Month 12 and Month 24 (end of treatment) of the OLFUS-VIPES study | 
| Change From VIPES Baseline in Peanut-Specific Immunoglobulin E (IgE) at Months 6, 12, 18 and 24 | The change from the VIPES Baseline in peanut-specific IgE values at Months 6, 12, 18 and 24 of the OLFUS-VIPES study are presented according to whether participants received Viaskin Peanut or placebo during the VIPES study. | VIPES Baseline to Months 6, 12, 18 and 24 (end of treatment) of the OLFUS-VIPES study | 
| Change From VIPES Baseline in Peanut-Specific Immunoglobulin G Subtype 4 (IgG4) at Months 6, 12, 18 and 24 | The change from the VIPES Baseline in peanut-specific IgG4 values at Months 6, 12, 18 and 24 of the OLFUS-VIPES study are presented according to whether participants received Viaskin Peanut or placebo during the VIPES study. | VIPES Baseline to Months 6, 12, 18 and 24 (end of treatment) of the OLFUS-VIPES study | 
| Change From VIPES Baseline in Wheal Diameter During Skin Prick Testing at Months 6, 12, 18 and 24 | The change from the VIPES Baseline in the wheal diameter from the undiluted skin prick tests at Months 6, 12, 18 and 24 of the OLFUS-VIPES study are presented according to whether participants received Viaskin Peanut or placebo during the VIPES study. | VIPES Baseline to Months 6, 12, 18 and 24 (end of treatment) in the OLFUS-VIPES study | 

 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)