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

Study Overview
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Brief Summary
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This is 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) subcutaneous injection every 4 weeks (SCq4w) in participants with a medically confirmed diagnosis of IgE-mediated peanut allergy.

Detailed Description
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This is 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) subcutaneous injection every 4 weeks (SCq4w) in participants with a medically confirmed diagnosis of IgE-mediated peanut allergy. Participants will be 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 will receive the first dose of blinded ligelizumab treatment at the Week 8 visit. Participants initially assigned to the 16-week placebo arm will receive 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.

Official Title
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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

Conditions
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Allergy, Peanut

Intervention / Treatment
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* Drug: ligelizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants who are ≥ 6 and ≤ 55 years of age at the time of signing informed consent/assent. Documented medical history of allergy to peanuts or peanut-containing foods. Positive peanut-specific immunoglobulin E (peanut sIgE), ≥ 0.35 kUA/L at Screening visit 1 (Screening 1). Positive skin prick test (SPT) for peanut allergen at Screening 1 defined as an average diameter (Longest diameter and mid-point orthogonal diameter) ≥ 4 mm wheal compared to saline control. 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 fulfillment of all other eligibility criteria. Participants must weigh ≥ 20 kg at Screening 1. Exclusion Criteria: Total IgE >2000 IU/mL at Screening 1. History of severe or life-threatening hypersensitivity event needing an ICU admission or intubation within 60 days prior to baseline DBPCFC (Screening visit 2). Participants with uncontrolled asthma (according to GINA guidelines, GINA 2020) who meet any of the following criteria: FEV1 <80% of subject's predicted normal value at Screening visit 1 One hospitalization for asthma within 12 months prior to Screening visit 1 Other protocol-defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ligelizumab 240 mg<br>ligelizumab 240 mg subcutaneous injection for 52 weeks | Drug: ligelizumab<br>* Subcutaneous injection once every 4 weeks<br>|
| Experimental: ligelizumab 120 mg<br>ligelizumab 120 mg subcutaneous injection for 52 weeks | Drug: ligelizumab<br>* Subcutaneous injection once every 4 weeks<br>|
| Experimental: Placebo 8 weeks and ligelizumab 120 mg<br>Placebo subcutaneous injection for first 8 weeks and ligelizumab 120 mg subcutaneous injection for 44 weeks | Drug: ligelizumab<br>* Subcutaneous injection once every 4 weeks<br>Drug: Placebo<br>* Subcutaneous injection once every 4 weeks<br>|
| Experimental: Placebo 16 weeks and ligelizumab 120 mg/240 mg<br>Placebo subcutaneous injection for first 16 weeks and ligelizumab 120 mg OR 240 mg subcutaneous injection for 36 weeks | Drug: ligelizumab<br>* Subcutaneous injection once every 4 weeks<br>Drug: Placebo<br>* Subcutaneous injection once every 4 weeks<br>|
| Experimental: Placebo 8 weeks and ligelizumab 240 mg<br>Placebo subcutaneous injection for first 8 weeks and ligelizumab 240 mg subcutaneous injection for 44 weeks | Drug: ligelizumab<br>* Subcutaneous injection once every 4 weeks<br>Drug: Placebo<br>* Subcutaneous injection once every 4 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who can tolerate a single dose of ≥ 600 mg (1044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms at Week 12 | Responder status is defined as tolerating a single dose of ≥ 600 mg (1044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms during the double blind placebo controlled food challenge (DBPCFC) conducted at Week 12 | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who can tolerate a single dose of ≥ 1000 mg (2044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms at Week 12 | Responder status is defined as tolerating a single dose of ≥ 1000 mg (2044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms during the DBPCFC conducted at Week 12 | Week 12 | 
| Proportion of participants who can tolerate a single dose of 3000 mg (5044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms at Week 12 | Responder status is defined as tolerating a single dose of 3000 mg (5044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms during the DBPCFC conducted at Week 12 | Week 12 | 
| Maximum severity of symptoms occurring at any challenge dose of peanut protein up to and including 1000 mg at Week 12 | Maximum severity of symptoms will be assessed during the DBPCFC conducted at Week 12. Symptom severity will be categorized as 4 levels: None, Mild, Moderate, Severe | Week 12 | 
| Proportion of participants who can tolerate a single dose of ≥ 1000 mg (2044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms at Week 52 | Responder status is defined as tolerating a single dose of ≥ 1000 mg (2044 mg cumulative tolerated dose) of peanut protein without dose-limiting symptoms during DBPCFC conducted at Week 52 | Week 52 | 
| Change in maximum tolerated dose (MTD) of peanut protein without dose-limiting symptoms during the DBPCFC at Week 52 compared to Week 12 | Change in MTD of peanut protein without dose-limiting symptoms at Week 52 compared to Week 12. Dose-limiting symptoms indicate a true allergic reaction occurring during administration of a single dose of peanut protein at the DBPCFC that should preclude the administration of any further doses in the view of the investigator. | Week 12 and Week 52 | 
| Change from baseline in peanut-specific IgE at Week 12, Week 16 and Week 52 | Change from baseline of serum levels of peanut-specific immunoglobulin E (IgE) | Baseline, Week 12, 16 and 52 | 
| Change from baseline in peanut-specific IgG4 at Week 12, Week 16 and 52 | Change from baseline of serum levels of peanut-specific immunoglobulin G4 (IgG4) | Baseline, Week 12, 16 and 52 | 
| Change from baseline in SPT mean wheal diameters at Week 16, Week 56 and Week 68 | Change from baseline (screening) in skin prick test (SPT) mean wheal diameters. | Baseline, Week 16, 56 and 68 | 
| Change from baseline in total and domain scores in the FAQLQ by age and responder (subject and/or caregiver) | The impact of ligelizumab on the health-related quality of life (HRQoL) of participants with a food allergy will be assessed by Food Allergy Quality of Life Questionnaire (FAQLQ) | Baseline, Week 12 and 56 | 
| Change from baseline in total and domain scores in the FAIM by age and responder (subject and/or caregiver) | The impact of ligelizumab on the health-related quality of life (HRQoL) of participants with a food allergy will be assessed by Food Allergy Independent Measure (FAIM). | Baseline, Week 12 and 56 | 
| Change from baseline in total and domain scores in the SF-36v2 by age and responder (subject and/or caregiver) | The impact of ligelizumab on the health-related quality of life (HRQoL) of participants with a food allergy will be assessed by a Medical Outcomes Study 36-Item Short Form Version 2 (SF-36v2). | Baseline, Week 12 and 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food allergy, Peanut allergy, Oral food challenge, IgE, ligelizumab