The PEPITES study evaluates the efficacy and safety of Viaskin Peanut 250 µg peanut protein to induce desensitization to peanut in peanut-allergic children 4 through 11 years of age after a 12-month treatment by epicutaneous immunotherapy (EPIT).

This is a 12-month, Phase III, double-blind, placebo-controlled, randomized study to assess the efficacy and safety of Viaskin Peanut, dosed at 250µg peanut protein (per patch) in peanut-allergic children from 4 through 11 years of age.

The overall maximum study duration for each subject is approximately 61 weeks (6-week screening period, 12-month treatment period and 2-week follow-up period).

During the screening period, subjects will undergo a first screening visit and an entry double-blind, placebo-controlled food challenge (DBPCFC) to peanut to confirm their allergy and their entry peanut eliciting dose (ED). The starting dose of the challenge will be 1 mg peanut protein and will escalate up to a highest dose of 300mg peanut protein. Subjects who react at or below the dose of 300mg peanut protein are considered eligible.

Randomization of eligible subjects will occur in a 2:1 ratio to Viaskin Peanut dosed at 250µg peanut protein (active treatment) or placebo. Subjects will be stratified at randomization by their entry/screening DBPCFC ED in 1 of the following 2 strata and by study center:

• Stratum 1: children with a screening ED of 1mg, 3mg or 10mg;
• Stratum 2: children with a screening ED of 30mg, 100mg or 300mg.

Subjects will apply a Viaskin patch containing either peanut protein or placebo daily for a period of 12 months. At Month 12, a post-treatment DBPCFC to peanut will be performed, with a starting dose of 1 mg peanut protein with escalation up to a highest dose of 2,000 mg peanut protein. This evaluation will help determine the primary efficacy endpoint of this pivotal study.

Main Inclusion Criteria:

1. Male or female children aged 4 through 11 years;

2. Physician-diagnosis of peanut allergy or children with a well documented medical history of IgE-mediated symptoms after ingestion of peanut and currently following a strict peanut-free diet, but without a physician diagnosis;

3. Peanut-specific IgE level (ImmunoCAP system) >0.7 kU/L;

4. Positive peanut skin prick test (SPT) with a largest wheal diameter:

   • ≥6 mm for children 4 through 5 years of age at Visit 1,
   • ≥8 mm for children 6 years and above at Visit 1;

5. Positive DBPCFC at ≤300 mg peanut protein.

Main Exclusion Criteria:

1. History of severe anaphylaxis to peanut with any of the following symptoms: hypotension, hypoxia, neurological compromise (collapse, loss of consciousness or incontinence);

2. Generalized dermatologic disease

3. Diagnosis of mast cell disorders, including mastocytosis or uricaria pigmentosa as well as hereditary or idiopathic angioedema;

4. Diagnosis of asthma that fulfills any of the following criteria:

   • Uncontrolled persistent asthma as defined by National Asthma Education and Prevention Program Asthma guidelines 2007 or by Global Initiative for Asthma guidelines 2015,
   • Asthma treated with either a high daily high dose of inhaled corticosteroid or with a combination therapy of a medium or high daily dose of inhaled corticosteroid with a long acting inhaled β2 agonist or with a combination therapy of a high daily dose of inhaled corticosteroid with a long acting inhaled β2 agonist. Asthmatic subjects treated with a medium daily dose of inhaled corticosteroids are eligible. Intermittent asthmatic subjects who require intermittent use of inhaled corticosteroids for rescue are also eligible,
   • Two or more systemic corticosteroid courses for asthma in the past year or 1 oral corticosteroid course for asthma within 3 months prior to Visit 1, or during screening period,
   • Prior intubation/mechanical ventilation for asthma within 1 year prior to Visit 1, or during screening;

5. Receiving β-blocking agents, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium channel blockers or tricyclic antidepressant therapy;

6. Received anti-tumor necrosis factor drugs or anti-IgE drugs (such as omalizumab) or any biologic immunomodulatory therapy within 1 year prior to Visit 1, during screening period or during study participation;

7. Use of systemic long-acting corticosteroids within 12 weeks prior to Visit 1 and/or use of systemic short-acting corticosteroids within 4 weeks prior to Visit 1 or during screening;

8. Prior or concomitant history of any immunotherapy to any food;

9. Receiving or planning to receive any aeroallergen immunotherapy during their participation in the study. Aeroallergen immunotherapy must be discontinued at the time of Visit 1;

10. Any disorder in which epinephrine is contraindicated such as coronary artery disease, uncontrolled hypertension, or serious ventricular arrhythmias.