A three-year, multi-center, double-blind, extension study to evaluate the long-term safety and efficacy of ligelizumab in patients who completed ligelizumab’s Phase III studies in food allergy

The primary objective of this study is to evaluate the long-term **safety** and tolerability of **ligelizumab** in participants with **food allergy**. This is clinically relevant as it aims to ensure that the therapeutic use of ligelizumab is safe for long-term administration, which is crucial for managing chronic conditions such as food allergies.

Secondary objectives include: - Describing the long-term efficacy of ligelizumab as measured by the tolerance of an allergen food protein during an open-label oral food challenge (OFC) at scheduled timepoints. - Assessing the safety and tolerability of ligelizumab in all participants who are administered the study treatment at home by self-administration or by a parent/caregiver. - Evaluating the long-term impact of ligelizumab on the health-related quality of life (HRQoL) of patients with food allergy. These objectives are important for understanding the broader implications of ligelizumab treatment, including its effectiveness in real-world settings and its impact on patients' quality of life.

The clinical trial involves a total of **495 participants** who have been diagnosed with **food allergy**. The study population includes both male and female subjects, encompassing a broad age range from children to adults. Participants were selected based on their completion of the treatment period in any ligelizumab Phase III studies related to food allergy. The trial population includes individuals who are willing to adhere to study visits and procedures, including receiving injections and participating in an open-label oral food challenge. Participants are required to continue avoiding exposure to allergens and any other foods they are allergic to throughout the study. The trial also includes a vulnerable population, indicating that special considerations are in place to ensure their safety and well-being. The general health status of participants is such that they are able to safely continue into the study as judged by the investigator. Lifestyle considerations such as diet are significant, as participants must adhere to dietary restrictions related to their allergies.

The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the long-term safety and efficacy of **ligelizumab** in patients with **food allergy** who have completed previous Phase III studies. The trial is expected to span a duration of approximately six years, with an estimated end date in July 2029. Participants will be involved in the study for a maximum treatment period of 156 weeks. The trial includes several key phases, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as completion of prior ligelizumab studies and the ability to adhere to study procedures. Following the screening, participants will undergo regular follow-up visits to monitor safety and efficacy outcomes, including the incidence of treatment-emergent adverse events (AEs) and serious adverse events (SAEs).

The study visits are structured to ensure comprehensive data collection and participant safety. The inclusion visit will involve obtaining informed consent and assessing the participant's medical history and current health status. Subsequent follow-up visits will occur at scheduled intervals, during which participants will receive the study treatment and undergo assessments such as the open-label oral food challenge (OL-OFC) to evaluate their tolerance to peanut protein. The primary endpoint of the study is the overall incidence and exposure-adjusted occurrence rates of treatment-emergent AEs and SAEs. Secondary endpoints include the proportion of participants tolerating a single dose of ≥ 600 mg of peanut protein without dose-limiting symptoms and summaries of total scores in the Food Allergy Quality of Life Questionnaire (FAQLQ), Food Allergy Independent Measure (FAIM), and SF-36v2 by age and responder.

The end-of-study visit will mark the conclusion of the participant's involvement, during which final assessments will be conducted to evaluate the long-term safety and efficacy of the treatment. Participants may be withdrawn from the study early if they experience significant adverse events, fail to adhere to study protocols, or withdraw consent. The trial's design ensures rigorous monitoring and data collection to achieve its primary objective of evaluating the long-term safety and tolerability of ligelizumab in individuals with food allergy.

The clinical trial involves several treatments, including both experimental and non-experimental medications. **Ligelizumab**, marketed under the product name QGE031, is an experimental medication used in this study. It is administered as a **solution for injection in a pre-filled syringe**. The active substance, ligelizumab, is a protein classified under "Protein - Other." The maximum daily dose is 240 mg, with a total maximum dose of 9600 mg over a treatment period of 156 weeks. The route of administration is **subcutaneous use**.

**PCM001** is another experimental treatment in the form of **granules for oral suspension**. The active substance is a defatted powder of **Arachis hypogaea L., semen (peanuts)**. The maximum daily dose is 5044 mg, with a total maximum dose of 45396 mg over a treatment period of 9 weeks. The route of administration is **oral use**.

**Salbutamol** is used as an auxiliary treatment in two forms: **inhalation powder** and **nebuliser solution**. The active substance is salbutamol, a chemical compound. The maximum daily dose for both forms is 20 mg, with a total maximum dose of 24080 mg over a treatment period of 172 weeks. The route of administration for both forms is **inhalation use**.

**Epinephrine** is also used as an auxiliary treatment, provided as a **solution for injection in a pre-filled pen**. The active substance is epinephrine, a chemical compound. The maximum daily dose is 0.9 mg, with a total maximum dose of 1083.60 mg over a treatment period of 172 weeks. The route of administration is **intramuscular use**.

A **placebo** is included in the study, designed to mimic the QGE031 120 mg/mL solution for injection in a pre-filled syringe. The placebo does not contain any active substance and serves as a control to evaluate the efficacy of the experimental treatment.

Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the treatment protocol. The trial aims to evaluate the long-term safety and efficacy of ligelizumab in patients with food allergies, following their completion of Phase III studies.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint focuses on the overall incidence and exposure-adjusted occurrence rates of treatment-emergent adverse events (AEs) and serious adverse events (SAEs). Secondary endpoints include the proportion of participants tolerating a single dose of ≥ 600 mg of peanut protein without dose-limiting symptoms during an open-label oral food challenge (OL-OFC) at scheduled timepoints. Additionally, summaries of total scores in the Food Allergy Quality of Life Questionnaire (FAQLQ), Food Allergy Independent Measure (FAIM), and SF-36v2 will be evaluated by age and responder (participants and/or caregiver) at scheduled timepoints.

The efficacy parameters will be collected and analyzed at various scheduled timepoints throughout the study. The open-label oral food challenge will be conducted to assess the tolerance to peanut protein, while the FAQLQ, FAIM, and SF-36v2 will be used to gather patient-reported outcomes. These tools are validated instruments designed to measure quality of life and health status in participants with food allergies. The data collected will be analyzed to determine the long-term efficacy of **ligelizumab** in participants who have completed previous Phase III studies in food allergy.