Efficacy and Safety of QGE031 (Ligelizumab) in Patients With Peanut Allergy

A 52 Week, Multi-center, Randomized, Double-blind Placebo-controlled Study to Assess the Clinical Efficacy and Safety of Ligelizumab (QGE031) in Decreasing the Sensitivity to Peanuts in Patients With Peanut Allergy

This was a 52-week, Phase 3 multi-center, randomized, double-blind and placebo-controlled study to assess the safety and clinical efficacy of two dosing regimens of ligelizumab (240 mg and 120 mg) SC q4w (subcutaneous injection every 4 weeks) in participants with a medically confirmed diagnosis of Immunoglobulin E (IgE) mediated peanut allergy.

Participants were randomized to ligelizumab 240 mg, ligelizumab 120 mg, or placebo (5 treatment arms, randomization ratio of 2:2:2:2:1) for the double-blind placebo-controlled treatment period (up to Week 12).

Participants initially assigned to the 8-week placebo arms received the first dose of blinded ligelizumab treatment at the Week 8 visit. Participants initially assigned to the 16-week placebo arm received the last dose of placebo before the Double Blind Placebo Controlled Food Challenge (DBPCFC) at Week 12 and the first dose of blinded ligelizumab treatment at the Week 16 visit.

At the start of the study, recruitment was restricted to 12-55-year-old participants. After approximately 60 adolescent participants (defined as 12-17 yrs of age) had completed all Week 12 assessments, an interim analysis (IA1) on Pharmacokinetics (PK) and selected Pharmacodynamics (PD) data (total IgE and basophil bound High affinity immunoglobulin E receptor 1 (FcƐRI)) was performed (safety was reviewed by a Data Monitoring Committee - DMC). Independent sponsor members who were responsible for PK/ PD data analysis and Modeling & Simulation were unblinded to the results of this interim analysis. The planned intent of this analysis was to confirm the dosing strategy for the youngest age group, 6-11 yrs and once the dose was to be confirmed, recruitment was supposed to be open for this age group. However, Novartis made a strategic decision to close recruitment in the study CQGE031G12301 and to terminate the study early, once all eligible participants in the study had completed week 12 assessments and the 16-week safety follow-up period. This decision was based on a blinded data review, which showed evidence of efficacy without the detection of any safety signal and that efficacy may be optimized with a different dosing regimen. Due to this decision, the final population size was 211, with only adolescent and adult participants (12 - 17yrs, and 18 - 55yrs) recruited.

Key Inclusion Criteria:

1. Signed informed consent and/or assent (where applicable) was obtained prior to study participation. Participant (and parent/legal guardian) was able to understand and provide informed consent and assent, as applicable. If a minor participant providing assent reaches the age of legal majority (as defined by local law), he/she was re-consented (ICF) at the next study visit.
2. Male or female participants who were 6 to 55 yrs of age at the time of signing informed consent/assent.
3. Documented medical history of allergy to peanuts or peanut-containing foods.
4. Positive peanut-specific IgE (peanut sIgE), ≥ 0.35 kUA/L at Screening Visit 1.
5. Positive SPT for peanut allergen at Screening Visit 1. This is defined as the average diameter (longest diameter and mid-point orthogonal diameter) ≥ 4 mm wheal compared to the negative control.
6. A positive peanut DBPCFC at baseline (Screening Visit 2, Part 1 and Part 2 DBPCFC) defined as the occurrence of dose-limiting symptoms at a single dose ≤ 100 mg of peanut protein. Eligibility to proceed with the DBPCFC requires presence of all inclusion and absence of all exclusion criteria.
7. Participants must weigh ≥ 20 kg at Screening Visit 1.
8. Participants must be able to receive injections (study treatment), participate in the DBPCFC, and must be willing to continue avoiding exposure to peanuts and any other foods that they are allergic to throughout this study.

Key Exclusion Criteria:

1. History of hypersensitivity to ligelizumab or its excipients, or to other biologics (i.e., to murine, chimeric or human antibodies).

2. Hypersensitivity or intolerance to any of the matrix components used within the material for the oral food challenge.

3. History of severe or life-threatening hypersensitivity event needing an ICU (intensive care unit) admission or intubation within 60 days prior to baseline DBPCFC (Screening Visit 2).

4. Total IgE >2000 IU/mL at Screening Visit 1.

5. Participants with uncontrolled asthma (according to Global Initiative for Asthma (GINA) guidelines, GINA 2020) who meet any of the following criteria:

   • FEV1 <80% of participant's predicted normal value at Screening Visit 1
   • One hospitalization for asthma within 12 months prior to Screening Visit 1

6. Current or previous history of a mast cell disorder, including mastocytosis.

7. Platelets < 100'000/μL at Screening Visit 1.

8. Female participants not on oral contraception with a stable dose for a minimum of 3 months prior to taking study treatment.

9. Participants with evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines at Screening Visit 1 (before start of Screening Visit 2). If stool testing is positive for pathogenic organisms, the participant should not be randomized and should not be allowed to be rescreened.