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
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 211
- 试验地点
- 30
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 6 Years 至 55 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Male or female participants who were 6 to 55 yrs of age at the time of signing informed consent/assent.
- •Documented medical history of allergy to peanuts or peanut-containing foods.
- •Positive peanut-specific IgE (peanut sIgE), ≥ 0.35 kUA/L at Screening Visit
- •Positive SPT for peanut allergen at Screening Visit
- •This is defined as the average diameter (longest diameter and mid-point orthogonal diameter) ≥ 4 mm wheal compared to the negative 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 presence of all inclusion and absence of all exclusion criteria.
- •Participants must weigh ≥ 20 kg at Screening Visit
- •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.
排除标准
- •History of hypersensitivity to ligelizumab or its excipients, or to other biologics (i.e., to murine, chimeric or human antibodies).
- •Hypersensitivity or intolerance to any of the matrix components used within the material for the oral food challenge.
- •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).
- •Total IgE >2000 IU/mL at Screening Visit
- •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
- •Current or previous history of a mast cell disorder, including mastocytosis.
- •Platelets < 100'000/μL at Screening Visit
- •Female participants not on oral contraception with a stable dose for a minimum of 3 months prior to taking study treatment.
- •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.
研究组 & 干预措施
ligelizumab 240 mg
ligelizumab 240 mg subcutaneous injection for 52 weeks
干预措施: ligelizumab (Drug)
ligelizumab 120 mg
ligelizumab 120 mg subcutaneous injection for 52 weeks
干预措施: ligelizumab (Drug)
Placebo 8 weeks and ligelizumab 120 mg
Placebo subcutaneous injection for first 8 weeks and ligelizumab 120 mg subcutaneous injection for 44 weeks
干预措施: ligelizumab (Drug)
Placebo 8 weeks and ligelizumab 120 mg
Placebo subcutaneous injection for first 8 weeks and ligelizumab 120 mg subcutaneous injection for 44 weeks
干预措施: Placebo (Drug)
Placebo 16 weeks and ligelizumab 120 mg/240 mg
Placebo subcutaneous injection for first 16 weeks and ligelizumab 120 mg OR 240 mg subcutaneous injection for 36 weeks
干预措施: ligelizumab (Drug)
Placebo 16 weeks and ligelizumab 120 mg/240 mg
Placebo subcutaneous injection for first 16 weeks and ligelizumab 120 mg OR 240 mg subcutaneous injection for 36 weeks
干预措施: Placebo (Drug)
Placebo 8 weeks and ligelizumab 240 mg
Placebo subcutaneous injection for first 8 weeks and ligelizumab 240 mg subcutaneous injection for 44 weeks
干预措施: ligelizumab (Drug)
Placebo 8 weeks and ligelizumab 240 mg
Placebo subcutaneous injection for first 8 weeks and ligelizumab 240 mg subcutaneous injection for 44 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
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
时间窗: Week 12
Responder rate was defined as the percentage of participants 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. The cumulative tolerated dose is the sum of the tolerated doses, not including the reactive dose. 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. Symptoms that require administration of any rescue medication were considered dose-limiting symptoms. Participants with treatment discontinuation or missing more than 1 doses of study drug prior to Week 12 due to reasons other than operational complications caused by public health emergency were considered non-responders.
次要结局
- 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(Week 12)
- 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(Week 12)
- Percentage of Maximum Severity of Symptoms Occurring at Any Challenge Dose of Peanut Protein up to and Including 1000 mg at Week 12(Week 12)
- 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(Week 12)
- Percentage of Participants Who Tolerated the Specified Peanut Protein Dose Without Dose-limiting Symptoms at Week 52(Week 52)
- Change From Baseline in Maximum Tolerated Dose (MTD) of Peanut Protein Without Dose-limiting Symptoms During the DBPCFC at Week 12 and Week 52(Baseline, Week 12, Week 52)
- Change From Baseline in Peanut-specific Immunoglobulin E (IgE) at Week 12 and Week 52(Baseline, Week 12, Week 52)
- Change From Baseline in Peanut-specific Immunoglobulin G4 (IgG4) at Week 12 and Week 52(Baseline, Week 12, Week 52)
- Change From Baseline in Skin Prick Test (SPT) Mean Wheal Diameters at Week 16/Week 56(Baseline, Week 16/Week 56)
- Change From Baseline in Total and Domain Scores in the Food Allergy Quality of Life Questionnaire (FAQLQ) Teenager Form (FAQLQ-TF)(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)))
- Change From Baseline in Total and Domain Scores in the Food Allergy Quality of Life Questionnaire (FAQLQ) Adult Form (FAQLQ-AF)(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)))
- Change From Baseline in Total Scores in the Food Allergy Independent Measure (FAIM) - Teenager Form (FAIM-TF)(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)))
- Change From Baseline in Total Scores in the Food Allergy Independent Measure (FAIM) - Adult Form (FAIM-AF)(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)))
- Change From Baseline in the SF-36v2 Physical Component Score (PCS) and Mental Component Score (MCS)(Baseline, Week 12 Part 2 (3 Days After Day 2 Oral Food Challenge (OFC)))