A Phase 3, Double-blind, Placebo-controlled, Randomized Study to Assess the Efficacy and Safety of Epicutaneous Immunotherapy with DBV712 250 μg in 4-7-year-old Children with Peanut Allergy (VITESSE)

The primary objective of this study is to assess the **efficacy** and safety of DBV712 250 µg in inducing desensitization to peanuts in children aged 4-7 years with a peanut allergy over a 12-month double-blind, placebo-controlled treatment period. This is clinically relevant as peanut allergy is a significant health concern in children, often leading to severe allergic reactions, and effective desensitization could improve patient outcomes and quality of life.

Secondary objectives include evaluating the magnitude of effect of DBV712 250 µg in inducing desensitization to peanuts in the same demographic over the same treatment period. This will provide further insights into the potential benefits and limitations of the treatment, contributing to a comprehensive understanding of its clinical utility.

The clinical trial involves a total of **474 participants** who are children aged 4 to 7 years, diagnosed with a **peanut allergy**. The study population includes both male and female subjects, and it is noted that the participants are considered a vulnerable population due to their young age. Participants were selected based on specific criteria, including a physician-diagnosed peanut allergy or a well-documented medical history of IgE-mediated reactions to peanuts. All participants are required to follow a strict peanut-free diet and have access to emergency medications, including self-injectable epinephrine, along with a current food allergy emergency action plan. The trial ensures that participants have a documented serum peanut-specific IgE level greater than 0.7 kUA/L and a positive skin prick test with a wheal diameter of at least 6 mm within the past six months. Additionally, participants must have an eliciting dose of 100 mg or less of peanut protein at the screening double-blind, placebo-controlled food challenge. The study requires signed informed consent from a legally authorized representative and assent from children aged 7 years, or as per country-specific regulations. Participants and their caregivers must be willing to comply with all study requirements during the trial period.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of epicutaneous immunotherapy using DBV712 250 µg in children aged 4 to 7 years with **peanut allergy**. The trial aims to assess the ability of DBV712 to induce desensitization to peanut allergens over a 12-month treatment period. Participants will be randomly assigned to receive either the active treatment or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring the study's double-blind nature. The trial is expected to commence recruitment on January 18, 2024, and conclude by May 30, 2029.

Study visits are structured to include an initial screening visit, multiple follow-up visits, and a final end-of-study visit. The screening visit will confirm eligibility based on criteria such as age, documented peanut allergy, and specific **IgE** levels. Follow-up visits will occur periodically throughout the 12-month treatment phase to monitor safety, adherence, and response to treatment. The end-of-study visit will evaluate the primary and secondary endpoints, including the percentage of treatment responders and changes in the eliciting dose (ED) of peanut protein.

Participant involvement is anticipated to last for the entire 12-month treatment period, with conditions for early termination including severe adverse events, non-compliance with study protocols, or withdrawal of consent. The primary endpoints focus on the percentage of treatment responders, defined by an increase in the ED of peanut protein, while secondary endpoints include changes in the cumulative reactive dose (CRD) and the severity of allergic reactions. Safety assessments will encompass adverse events, treatment-emergent adverse events, and any systemic allergic reactions. The trial's rigorous design and comprehensive monitoring aim to ensure the collection of robust data on the efficacy and safety of DBV712 in managing peanut allergy in young children.

The clinical trial involves the administration of several treatments, including both experimental and non-experimental medications. The **Viaskin Peanut** is an experimental treatment in the form of a **cutaneous patch**. It contains **arachis hypogaea extract** as the active substance. The patch is designed for cutaneous use, with a maximum daily dose of 250 micrograms and a total dose of 273.75 milligrams over a treatment period of 36 months. The patch is applied once daily, and participant compliance is monitored through regular follow-ups.

Another experimental treatment is the **0% Peanut Challenge Meal (PCM) base**, which is provided as **granules for oral suspension**. The active substance is a **defatted powder of arachis hypogaea L., semen (peanuts)**. This formulation is used as a placebo in the study, with no active peanut protein content. The granules are administered orally, with a maximum treatment period of 4 months. The dosing schedule is determined based on the study protocol, and compliance is assessed through participant diaries and clinical visits.

The study also includes the **20% Peanut Challenge Meal (PCM) base**, which is similar in form to the 0% PCM base but contains a higher concentration of the active substance. The maximum daily dose is 4043 milligrams, with a total dose of 26445 milligrams over an 8-month period. This formulation is used to assess the response to varying concentrations of peanut protein.

The **0.67% Peanut Challenge Meal (PCM) base** is another formulation used in the study, with the same pharmaceutical form and active substance as the other PCM bases. It is administered with a maximum daily dose of 4043 milligrams and a total dose of 26445 milligrams over 8 months. This formulation helps in evaluating the dose-response relationship in participants.

For diagnostic purposes, the study employs the **ALK 762 Jordnød Opløsning til priktest (Soluprick)**, a **solution for skin-prick test** containing **arachis hypogaea (762)**. This solution is used to confirm peanut allergy in participants. The maximum daily dose is 0.15 micrograms, with a total dose of 0.3 micrograms over a 2-day period. The solution is applied cutaneously, and results are monitored by trained clinical staff.

The **Soluprick Positive control** is another solution for skin-prick testing, containing **histamine dihydrochloride**. It serves as a positive control to ensure the accuracy of the skin-prick test results. The maximum daily dose is 0.03 micrograms, with a total dose of 0.06 micrograms over 2 days. This control is essential for validating the test outcomes.

The **Soluprick Negative control** is a solution for skin-prick testing containing **water for injection**. It acts as a negative control to confirm the absence of a reaction in non-allergic individuals. The solution is applied cutaneously, with no active dose, and is used over a 2-day period to ensure the reliability of the test results.

The study also includes a **DBV712 placebo cutaneous system**, which is identical to the DBV712 250 mcg system but lacks peanut proteins. This placebo is used to maintain blinding in the study and is applied cutaneously. The placebo system is crucial for comparing the effects of the active treatment against a non-active control.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint focuses on the percentage of treatment responders in the DBV712 250 μg group compared to the placebo group after 12 months of treatment. A subject is considered a treatment responder if the initial **eliciting dose (ED)** was ≤ 30 mg of peanut protein and the ED is ≥ 300 mg at the post-treatment double-blind, placebo-controlled food challenge (DBPCFC) at Month 12, or if the initial ED was > 30 mg and the ED is ≥ 600 mg at the post-treatment DBPCFC at Month 12.

Secondary endpoints include the cumulative reactive dose (CRD) of peanut protein after 12 months of treatment, the ED of peanut protein after 12 months, and the percentage of subjects with an ED ≥ 600 mg and ≥ 1000 mg peanut protein at Month 12. These will be compared between the DBV712 250 μg group and the placebo group, both overall and within each of the two screening ED subgroups. Additionally, the maximum severity of allergic reactions at baseline and Month 12 food challenge will be assessed in both groups.