Phase 3, Open-label Trial to Evaluate Safety, Pharmacokinetics, and Efficacy of Benralizumab in Children With Eosinophilic Diseases (CLIPS)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 14
- 试验地点
- 17
- 主要终点
- Serum Concentrations of Benralizumab
研究概览
简要总结
The main purpose of study is to assess the safety, tolerability, pharmacokinetics (PK), and efficacy of benralizumab.
详细描述
This study is open-label, multicentre, basket study to evaluate the safety, PK, pharmacodynamic (PD), efficacy, and immunogenicity of repeat dosing of benralizumab subcutaneous (SC) every 4 weeks (Q4W) in male and female children with rare eosinophilic diseases.
Paediatric participants with eosinophilic granulomatosis with polyangiitis (EGPA) will be enrolled in the first cohort.
Paediatric participants with hypereosinophilic syndrome (HES) will be enrolled in the second cohort. Additional cohorts in other eosinophilic diseases may be added in future protocol amendments.
The study consists of 3 periods:
- Screening period: 1 to 4 weeks
- Open-label treatment period: 52 weeks
- Open-label extension period: at least 52 weeks (plus safety follow-up [SFU] weeks after last investigational product [IP] administration)
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All Cohorts:
- •Male or female participants must be aged 6 to < 18 years of age at the time of signing the assent form and their caregiver signing the informed consent form.
- •Body weight greater than (>=) 15 kilograms (kg).
- •EGPA Cohort:
- •Therapy with corticosteroids: The prescribed dose of oral corticosteroids (OCS) (greater than [>] 0.1 milligrams per kilogram per day (mg/kg/day), max dose of 50 milligrams per day (mg/day) must be stable (that is, no adjustment of the dose) for at least 4 weeks prior to baseline (Visit 2).
- •Immunosuppressive therapy: If receiving immunosuppressive therapy, the dosage must be stable for at least 4 weeks prior to baseline (Visit 2).
- •HES Cohort:
- •Documented HES diagnosis, defined as history of persistent eosinophilia >1500 cells/µL without secondary cause on 2 examinations ≥1 month apart and evidence of eosinophil-mediated organ involvement.
- •Symptomatic active HES, or history of a prior flare, or considered eligible based on disease severity per investigator judgement.
- •AEC ≥1000 cells/µL at screening (Visit 1).
- •Documented negative testing for Fip1-like 1 gene fused with the platelet-derived growth factor receptor alpha gene (FIP1L1-PDGFR) fusion tyrosine kinase gene translocation.
排除标准
- •All Cohorts:
- •Any current malignancy or history of malignancy.
- •History of anaphylaxis to any biologic therapy or vaccine.
- •Known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory, or any other system abnormalities.
- •Previous receipt of benralizumab in an interventional clinical study.
- •EGPA Cohort:
- •Diagnosed with granulomatosis with polyangiitis (previously known as Wegener'granulomatosis) or microscopic polyangiitis.
- •EGPA relapse: any deterioration in EGPA and/or organ-threatening EGPA that per Investigator judgement renders participants unstable in their EGPA within 3 months prior to screening (Visit 1) and through first administration of IP at baseline (Visit 2).
- •Life-threatening EGPA: imminently life-threatening EGPA disease within 3 months prior to screening (Visit 1) and through first administration of IP at baseline (Visit 2), as per Investigator judgement.
- •HES Cohort:
- •Life-threatening HES or HES complications, as judged by the investigator.
- •Hypereosinophilia of unknown significance (HE-US).
- •Diagnosis of systemic mastocytosis.
研究组 & 干预措施
EGPA/HES Cohort: Benralizumab
Participants with greater than or equal to (>=) 35 kg weight will receive benralizumab dose-1 and participants with less than (<) 35 kg weight will receive benralizumab dose-2 as SC injection Q4W during the 52-week treatment period. All participants who complete the 52-week treatment period will be offered the opportunity to continue into an extension period.
干预措施: Benralizumab (Drug)
结局指标
主要结局
Serum Concentrations of Benralizumab
时间窗: Weeks 0, 12, 24, 25, 36, and 52
The PK of benralizumab will be evaluated.
Number of Participants with Adverse Events (AEs)
时间窗: From screening (Week -4 to -1) until Week 52
The safety and tolerability of benralizumab will be evaluated.
次要结局
- Change From Baseline in Peripheral Blood Eosinophil Count(From Baseline to Weeks 0, 12, 24, 36, 52)
- EGPA Cohort: Time to First EGPA Relapse(Up to 52 weeks)
- EGPA Cohort: Percentage of Participants with Remission at Week 24(At Week 24)
- Number of Participants with Positive Antidrug Antibody (ADA)(Weeks 0, 12, 24, 36, 48, and 52)
- HES Cohort: Time to first HES worsening/flare(Up to 52 weeks)
- HES Cohort: Percentage of participants who experience a HES worsening/flare(Up to 52 weeks)
- HES Cohort: Number of HES worsening/flares (annualised rate/year)(Up to 52 weeks)
- HES Cohort: Percentage of Participants requiring an increase in corticosteroid dose(Up to 52 weeks)
- HES Cohort: Time to first haematologic relapse(Up to 52 weeks)
- HES Cohort: Percentage of Participants with haematologic relapse(Up to 52 weeks)
- HES Cohort: Percentage of Participants who have AEC < 500 cells/μL for 24 weeks(Up to 52 weeks)
- HES Cohort: Patient Global Impression of Change (PGI-C) Score(Weeks 12, 24, 36 and 48)