Clinical trial NCT04984876: Efficacy and Safety of QGE031 (Ligelizumab) in Patients With Peanut Allergy
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Allergy, Peanut
Keywords: Food allergy
Peanut allergy
Oral food challenge
IgE
ligelizumab
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-08-02
Enrollment: 211
Sex: ALL
Minimum age (years): 6
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Tolerated a Single Dose of >= 600 mg (1044 mg Cumulative Tolerated Dose) of Peanut Protein Without Dose-limiting Symptoms at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants Who Tolerated a Single Dose of >= 1000 mg (2044 mg Cumulative Tolerated Dose) of Peanut Protein Without Dose-limiting Symptoms at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Tolerated a Single Dose of 3000 mg (5044 mg Cumulative Tolerated Dose) of Peanut Protein Without Dose-limiting Symptoms at Week 12
timeFrame: Week 12
measure: Percentage of Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein up to and Including 1000 mg at Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Tolerated a Single Dose of >= 1000 mg (2044 mg Cumulative Tolerated Dose) of Peanut Protein Without Dose-limiting Symptoms at Week 12 After 4 Weeks of Treatment
timeFrame: Week 12
measure: Percentage of Participants Who Tolerated the Specified Peanut Protein Dose Without Dose-limiting Symptoms at Week 52
timeFrame: Week 52
measure: Change From Baseline in Maximum Tolerated Dose (MTD) of Peanut Protein Without Dose-limiting Symptoms During the DBPCFC at Week 12 and Week 52
timeFrame: Baseline, Week 12, Week 52
measure: Change From Baseline in Peanut-specific Immunoglobulin E (IgE) at Week 12 and Week 52
timeFrame: Baseline, Week 12, Week 52
measure: Change From Baseline in Peanut-specific Immunoglobulin G4 (IgG4) at Week 12 and Week 52
timeFrame: Baseline, Week 12, Week 52
measure: Change From Baseline in Skin Prick Test (SPT) Mean Wheal Diameters at Week 16/Week 56
timeFrame: Baseline, Week 16/Week 56
measure: Change From Baseline in Total and Domain Scores in the Food Allergy Quality of Life Questionnaire (FAQLQ) Teenager Form (FAQLQ-TF)
timeFrame: Baseline, Week 12 Part 1 (10 Days Before Day 1 Oral Food Challenge (OFC)), Week 12 Part 2 (3 Days After Day 2 Oral Food Challenge (OFC))
measure: Change From Baseline in Total and Domain Scores in the Food Allergy Quality of Life Questionnaire (FAQLQ) Adult Form (FAQLQ-AF)
timeFrame: Baseline, Week 12 Part 1 (10 Days Before Day 1 Oral Food Challenge (OFC)), Week 12 Part 2 (3 Days After Day 2 Oral Food Challenge (OFC))
measure: Change From Baseline in Total Scores in the Food Allergy Independent Measure (FAIM) - Teenager Form (FAIM-TF)
timeFrame: Baseline, Week 12 Part 1 (10 Days Before Day 1 Oral Food Challenge (OFC)), Week 12 Part 2 (3 Days After Day 2 Oral Food Challenge (OFC))
measure: Change From Baseline in Total Scores in the Food Allergy Independent Measure (FAIM) - Adult Form (FAIM-AF)
timeFrame: Baseline, Week 12 Part 1 (10 Days Before Day 1 Oral Food Challenge (OFC)), Week 12 Part 2 (3 Days After Day 2 Oral Food Challenge (OFC))
measure: Change From Baseline in the SF-36v2 Physical Component Score (PCS) and Mental Component Score (MCS)
timeFrame: Baseline, Week 12 Part 2 (3 Days After Day 2 Oral Food Challenge (OFC))
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Allervie Clinical Research
state: Alabama
city: Scottsdale
country: United States
facility: Allergy and Immunology Associates
state: Arizona
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: San Jose
country: United States
facility: Allergy and Asthma Associates of Santa Clara Vally Center
state: California
city: Walnut Creek
country: United States
facility: Allergy and Asthma Clinical Research Inc
state: California
city: Aurora
country: United States
facility: UCHealth Outpatient Pavilion
state: Colorado
city: Colorado Springs
country: United States
facility: Asthma and Allergy Associates P C
state: Colorado
city: Denver
country: United States
facility: Colorado Allergy and Asthma Ctr PC
state: Colorado
city: Tampa
country: United States
facility: Univ of South Florida Asthma Allergy and Immunology CRU
state: Florida
city: Atlanta
country: United States
facility: Childrens Healthcare of Atlanta
state: Georgia
city: Marietta
country: United States
facility: Atlanta Allergy and Asthma Clinic
state: Georgia
city: Chicago
country: United States
facility: Ann and Robert H Lurie Childrens Hospital of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Louisville
country: United States
facility: Family Allergy and Asthma
state: Kentucky
city: Baltimore
country: United States
facility: Johns Hopkins Childrens Center
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Childrens Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Clinical Trials Office
state: Michigan
city: Ypsilanti
country: United States
facility: Respiratory Medicine Research Institute of Michigan
state: Michigan
city: Buffalo
country: United States
facility: UBMD Pediatrics
state: New York
city: New York
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: Mt Sinai Medical Center
state: New York
city: Chapel Hill
country: United States
facility: University Of NC At Chapel Hill
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Childrens Hospital MC
state: Ohio
city: Cincinnati
country: United States
facility: Bernstein Clinical Research Center
state: Ohio
city: Philadelphia
country: United States
facility: Childrens Hospital Of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Texas Childrens Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Allergy and Asthma Rsch
state: Washington
city: Brisbane
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Parkville
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Hamilton
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Ottawa
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Odense
country: Denmark
facility: Novartis Investigative Site
city: Angers Cedex 9
country: France
facility: Novartis Investigative Site
city: Lille
country: France
facility: Novartis Investigative Site
city: Toulouse
country: France
facility: Novartis Investigative Site
city: Vandoeuvre Les Nancy
country: France
facility: Novartis Investigative Site
city: Berlin
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Frankfurt
country: Germany
facility: Novartis Investigative Site
city: Padova
country: Italy
facility: Novartis Investigative Site
state: PD
city: Sagamihara-city
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Setagaya-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinagawa-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Utrecht
country: Netherlands
facility: Novartis Investigative Site
city: Esplugues De Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Barcelona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Madrid
country: Spain
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: