A Phase 3, Double-Blind, Placebo-Controlled, Randomized Study to Assess the Safety of Epicutaneous Immunotherapy with DBV712 250 µg in 1-through 3-year-old Children with Peanut Allergy

The primary objective of this study is to assess the 6-month safety profile of DBV712 250 µg in pediatric subjects aged 1 through 3 years with peanut allergy. This evaluation is clinically relevant as it focuses on establishing the tolerability and adverse event profile of epicutaneous immunotherapy in a particularly vulnerable toddler population, where safety data are critical for informing treatment decisions in early childhood allergic disease management.

No secondary objectives are defined for this trial.

The clinical trial enrolled a total of **396 participants** aged **1 through 3 years** with **peanut allergy**. Both **male** and **female** subjects were included in the study population. Participants were required to have a physician-diagnosed peanut allergy or high clinical suspicion, confirmed by specific immunological markers including **peanut-specific IgE** levels greater than 0.7 kUA/L and a positive **skin prick test** with a wheal diameter of at least 6 mm. Additionally, subjects demonstrated clinical reactivity through a positive **double-blind placebo-controlled food challenge** to peanut, with symptoms occurring at an eliciting dose of 300 mg peanut protein or less. All participants adhered to a strict **peanut-free diet** as a lifestyle requirement. The selection criteria ensured that subjects had access to emergency medications, including **auto-injectable epinephrine**, and maintained a current food allergy emergency action plan. This study population was classified as vulnerable due to the young age of participants.

This is a Phase 3, double-blind, placebo-controlled, randomized clinical trial designed to assess the safety of epicutaneous immunotherapy with DBV712 250 µg in children aged 1 through 3 years with peanut allergy. The study employs a randomized, double-blind, placebo-controlled design to evaluate the investigational medicinal product Viaskin Peanut (DBV712), which is a cutaneous patch containing 250 µg of arachis hypogaea extract administered via cutaneous use. The maximum daily dose is 250.00 µg, with a maximum total dose of 182500.00 µg over a treatment period of 24 months. The placebo comparator is the DBV712 Placebo Patch, which is identical to the active patch but without peanut proteins. Several auxiliary products are utilized in the study, including solutions for skin-prick test (Soluprick Positive control containing histamine dihydrochloride, Soluprick Negative control containing water for injection, and ALK 762 peanut allergen solution containing arachis hypogaea), as well as peanut food challenge oral paste formulations in low dose (6.6 mg/g peanut proteins), high dose (133.3 mg/g peanut proteins), and placebo formulation, all containing arachis hypogaea flour.

The estimated recruitment start date is November 10, 2025, with an estimated study end date of April 30, 2028. Eligible participants include children 1 through 3 years of age at Visit 1 with physician-diagnosed peanut allergy or high suspicion of peanut allergy. Inclusion criteria require peanut specific IgE greater than 0.7 kUA/L at screening, positive peanut skin prick test with a largest wheal diameter of at least 6 mm at screening, and positive double-blind placebo-controlled food challenge to peanut with symptoms meeting challenge stopping criteria at an eliciting dose of 300 mg peanut protein or less. Subjects must adhere to a strict peanut-free diet, have access to emergency medications including auto-injectable epinephrine and a current food allergy emergency action plan, and parents or caregivers must be willing to comply with all study requirements.

The primary objective is to assess the 6-month safety of DBV712 250 µg in subjects 1 through 3 years of age with peanut allergy. Primary endpoints include evaluation of adverse events and treatment emergent adverse events by system organ class and preferred term, maximum severity, duration, and relatedness to treatment, adverse events leading to discontinuation, severity of local cutaneous DBV712 system induced adverse events, and adverse events of special interest including local adverse events of special interest (severe local site reactions with loss of skin barrier integrity) and systemic adverse events of special interest (systemic allergic reactions including those leading to epinephrine use). Additional primary endpoints include adverse events leading to inhaled or systemic corticosteroid use, serious adverse events by system organ class and preferred terms and relatedness to treatment, laboratory data, physical examinations and vital signs, and assessment of pain and ease of removal of DBV712.

Secondary exploratory endpoints include change from baseline in peanut-specific IgE and IgG4, change from baseline in peanut-component-specific IgE and IgG4, change from baseline in peanut skin prick test mean wheal diameters, description of reactions triggered by peanut consumption during the study, SCORAD evolution over time, assessment of system adhesion and average daily application time, and parent or caregiver daily assessment of local skin reactions including itching, redness and swelling.

The study involves screening procedures including medical history, physical examination, vital signs assessment, skin prick testing with positive control (histamine dihydrochloride), negative control (water for injection), and peanut allergen solution, measurement of peanut-specific and peanut-component-specific IgE and IgG4 levels, and double-blind placebo-controlled food challenge using oral paste formulations at low dose, high dose, and placebo. Following successful screening and confirmation of eligibility, participants will be randomized to receive either DBV712 250 µg cutaneous patch or placebo patch applied daily for 24 months. Follow-up visits will occur at regular intervals to assess safety parameters, local skin reactions, adverse events, and collect blood samples for immunological assessments. The end-of-study visit will include final safety assessments and evaluation of all study endpoints. Participants may be withdrawn early from the study due to adverse events leading to discontinuation, withdrawal of consent by the legally authorized representative, protocol violations, or at the discretion of the investigator if continued participation is not in the best interest of the participant.

The experimental treatment consists of **Viaskin Peanut** (DBV712), a **cutaneous patch** containing 250 micrograms of **arachis hypogaea extract** (peanut extract). The product is an **epicutaneous** immunotherapy system of biological origin, designed as a combination product containing unmodified, lyophilized peanut extract. The patch is administered via **cutaneous use** with a maximum daily dose of 250 micrograms. The maximum total dose over the treatment period is 182,500 micrograms, administered over a maximum treatment period of 24 months. This formulation is designated as a **paediatric formulation**.

The **placebo** treatment consists of the DBV712 Placebo Patch, which is identical in design and composition to the DBV712 250 microgram patch but does not contain **peanut proteins**. The placebo patch maintains the same physical characteristics and application method as the active treatment to ensure blinding in this double-blind study.

Several auxiliary products are utilized for diagnostic purposes and assessment of **peanut allergy**. Soluprick Positive control is a **solution for skin-prick test** containing 10 mg/ml of **histamine dihydrochloride**, administered via **cutaneous use**. The maximum daily dose is 30 nanograms with a maximum total dose of 12 nanograms over a maximum treatment period of 4 days. This product is indicated for diagnosis of specific **IgE-mediated allergy**.

Soluprick Negative control is a **solution for skin prick test** containing **water for injection** as the active substance. It is administered via **cutaneous use** with a maximum treatment period of 4 days. The maximum daily dose and maximum total dose are both 0.00 milligrams. This product serves as a negative control for diagnosis of specific IgE-mediated allergy.

ALK 762 Jordnød (Soluprick) is a **solution for skin-prick test** containing **arachis hypogaea** allergen extract. It is administered via **cutaneous use** with a maximum daily dose of 0.15 nanograms and a maximum total dose of 0.60 nanograms over a maximum treatment period of 4 days. This product is indicated for diagnosis of specific IgE-mediated allergies to peanut allergen.

Peanut food challenge products are provided as **oral paste** formulations containing **arachis hypogaea flour** of biological origin. The low dose formulation contains 6.6 mg/g peanut proteins with a maximum daily dose of 30 milligrams and a maximum total dose of 88 milligrams over a maximum treatment period of 2 days. The high dose formulation contains 133.3 mg/g peanut proteins with a maximum daily dose of 1,000 milligrams and a maximum total dose of 1,800 milligrams over a maximum treatment period of 2 days. Both formulations are administered via **oral use** and are designated as paediatric formulations. Administration is performed using half-spherical spoons with various sizes available from 0.5 mL to 25 mL.

A placebo formulation of the peanut food challenge is also provided as an **oral paste**. Despite containing arachis hypogaea flour as a listed substance, this placebo formulation has a maximum daily dose and maximum total dose of 0.00 milligrams over a maximum treatment period of 2 days. It is administered via **oral use** using half-spherical spoons with various sizes available from 0.5 mL to 15 mL, and is designated as a paediatric formulation.

Efficacy will be assessed through exploratory evaluations measuring immunological and clinical parameters. Change from baseline in **peanut-specific IgE** and IgG4 levels will be measured, along with change from baseline in peanut-component-specific IgE and IgG4. Change from baseline in peanut skin-prick test mean wheal diameters will be evaluated. Reactions triggered by peanut consumption during the study will be described. SCORAD evolution over time will be assessed. System adhesion and average daily application time will be evaluated. Parent or caregiver daily assessment of local skin reactions, including itching, redness, and swelling, will be performed.