Long-term Evaluation of DBV712 in Pediatric Peanut Allergy: An Open-label Extension Study on Clinical Benefit and Safety

The primary objective of this study is to assess the **clinical benefit** of Viaskin Peanut after up to 3 years of epicutaneous immunotherapy (EPIT) in inducing or maintaining desensitization to peanuts in children with a **peanut allergy**. This is clinically relevant as it aims to provide a long-term therapeutic option for managing peanut allergies, which can significantly impact the quality of life and reduce the risk of severe allergic reactions. Additionally, the study seeks to evaluate the safety of long-term treatment with Viaskin Peanut in this pediatric population, ensuring that the therapy is not only effective but also safe for extended use.

The clinical trial involves a total of **276 participants** who are children with a **peanut allergy**. The study population includes both male and female subjects, specifically within the age range of 2 to 17 years. Participants were selected based on their completion of the EPITOPE study, which included a documented double-blind, placebo-controlled food challenge (DBPCFC) at Month 12. The trial does not involve a vulnerable population. Participants are expected to comply with all study requirements, as agreed upon by their parents or guardians. The trial aims to assess the clinical benefit and safety of Viaskin Peanut for inducing or maintaining desensitization to peanuts through epicutaneous immunotherapy over a period of up to three years. No specific lifestyle considerations such as diet or physical activity are highlighted for this study.

The clinical trial is designed to evaluate the long-term clinical benefit and safety of **Viaskin Peanut** in children with **peanut allergy**. This study is a randomized, double-blind, controlled trial with a duration of up to 36 months. Participants will be randomly assigned to receive either the active treatment or a placebo. The trial will include several key phases, starting with an inclusion visit, followed by multiple follow-up visits, and concluding with an end-of-study visit. The inclusion visit will involve screening procedures to confirm eligibility, including the completion of a double-blind, placebo-controlled food challenge (DBPCFC) at Month 12 of the preceding EPITOPE study. Follow-up visits will occur periodically to monitor the participants' response to treatment and assess any adverse events. The end-of-study visit will evaluate the overall outcomes and safety of the treatment.

Participants are expected to be involved in the study for the entire duration of 36 months unless specific conditions necessitate early termination. These conditions include the occurrence of serious adverse events, non-compliance with study protocols, or withdrawal of consent by the participant or their guardians. The primary endpoints of the study include the proportion of subjects achieving a specific level of desensitization to peanut protein and the assessment of treatment responders. Secondary endpoints will explore additional immunological markers and quality of life measures. The study aims to provide comprehensive data on the efficacy and safety of long-term treatment with Viaskin Peanut, contributing valuable insights into the management of peanut allergy in children.

The clinical trial involves the use of several treatments, including both experimental and non-experimental medications. The **experimental medication** is "Viaskin Peanut," a cutaneous patch containing **arachis hypogaea extract**. This patch is designed for cutaneous use and is applied to the skin. The maximum daily dose is 250 micrograms, with a total maximum dose of 273,750 micrograms over a treatment period of up to 36 months. This formulation is of biological origin and is specifically developed for pediatric use. The patch does not have a CE mark, indicating it is not certified for compliance with European health, safety, and environmental protection standards.

The study also includes a **placebo formulation** known as "Peanut food challenge, oral paste 'placebo'." This placebo is an oral paste containing **arachis hypogaea flour** and is administered orally. The maximum daily dose is 2000 milligrams, with a total maximum dose of 10,332 milligrams over a 6-month period. The placebo is not a pediatric formulation and is used to compare the effects of the experimental treatment.

Additionally, the trial utilizes two auxiliary treatments: "Peanut food challenge, oral paste 'low dose'" and "Peanut food challenge, oral paste 'high dose'." Both formulations contain **arachis hypogaea flour** and are administered orally. The low-dose paste contains 6.6 mg/g of peanut proteins, while the high-dose paste contains 133.3 mg/g of peanut proteins. Both have a maximum daily dose of 2000 milligrams and a total maximum dose of 10,332 milligrams over a 6-month period. These formulations are of biological origin and are pediatric formulations.

Participant compliance with the dosing schedule is monitored throughout the trial. The oral pastes are administered using a device described as a "1/2 Spherical spoon 0.5 ml," which has a CE mark, ensuring compliance with relevant standards. The trial aims to assess the long-term clinical benefit and safety of the Viaskin Peanut patch in peanut-allergic children, with a focus on maintaining desensitization to peanuts.

Efficacy in the clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the sustained clinical benefit of Viaskin Peanut in peanut-allergic children. The primary endpoints include the proportion of subjects reaching an eliciting dose (ED) of ≥1000 mg peanut protein after 1, 2, and 3 years of treatment, as well as the proportion of treatment responders. A treatment responder is defined as a subject whose baseline ED was >10 mg and reaches an ED of ≥1000 mg, or whose baseline ED was ≤10 mg and reaches an ED of ≥300 mg at post-baseline double-blind, placebo-controlled food challenges (DBPCFCs). Additional primary endpoints involve the proportion of subjects reaching cumulative doses of at least 1444 mg and 3444 mg peanut protein, and the proportion of subjects unresponsive to the highest dose of 2000 mg peanut protein.

Secondary endpoints will explore other aspects of treatment efficacy over the 3-year period, including changes in total IgE, peanut-specific IgE, and IgG4 levels, as well as levels specific to peanut protein components such as Ara h 1, Ara h 2, and Ara h 3. The Peanut Skin Prick Test (SPT) average wheal diameters will also be measured. Quality of life (QoL) will be assessed using Food Allergy Quality of Life Questionnaires (FAQLQ), Food Allergy Independent Measure (FAIM), and EQ-5D-5L scores. The study will also evaluate the enumeration and characterization of reactions triggered by accidental peanut consumption, epigenetic modifications of specific gene promoters, sensitization status to other allergens, and the evolution of the Scoring Atopic Dermatitis (SCORAD) index over time.