NCT04157348进行中（未招募）3 期
A Randomised, Double-blind, Active-controlled 52-week Study With an Open-label Extension to Evaluate the Efficacy and Safety of Benralizumab Compared to Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis (EGPA) in Patients Receiving Standard of Care Therapy (MANDARA Study)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- AstraZeneca
- 入组人数
- 140
- 试验地点
- 51
- 主要终点
- Number of Subjects Who Achieved Main Remission at Both Weeks 36 and 48
研究概览
简要总结
This is a randomized, double blind, active-controlled, parallel group, multicenter 52-week Phase 3 study to compare the efficacy and safety of benralizumab 30 mg versus mepolizumab 300 mg administered by subcutaneous (SC) injection in patients with relapsing or refractory EGPA on corticosteroid therapy with or without stable immunosuppressive therapy.
All patients who complete the 52-week double-blind treatment period on IP may be eligible to continue into an open label extension (OLE) period. The OLE period is intended to allow each patient at least 1 year of treatment with open-label benralizumab 30 mg administered SC (earlier enrolled patients may therefore be in the OLE for longer than 1 year).
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
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects age 18 years or older.
- •EGPA diagnosis based on history or presence asthma and eosinophilia (>1.0x10^9/L and/or >10% of leucocytes) and at least 2 of; biopsy with eosinophilic vasculitis or perivascular/granulomatous inflammation; mono-or polyneuropathy, non-fixed pulmonary infiltrates, sino-nasal abnormality; cardiomyopathy; glomerulonephritis; alveolar haemorrhage; palpable purpura; anti neutrophil cytoplasmic anti-body (ANCA) positivity (Myeloperoxidase or proteinease 3).
- •History of relapsing (at least 1 confirmed EGPA relapse within last 2 years and > 12 weeks prior to screening), or refractory (failure to attain remission, defined as BVAS=0 and oral corticosteroid (OCS) dose <=7.5 mg/day of prednisolone or equivalent, following standard induction regimen for at least 3 months and within 6 months prior to screening, or recurrence of symptoms upon OCS tapering at any dose of ≥7.5 mg/day prednisolone or equivalent.
- •If induction with glucocorticoidsalone, patient must have failed to attain remission after 3 months and the glucocorticoid dose must be ≥15 mg/day prednisolone or equivalent for the 4 weeks prior to randomization.
- •Must be on a stable dose of oral prednisolone or prednisone of ≥7.5 mg/day (but not >50mg/day) for at least 4 weeks prior to randomization.
- •If receiving immunosuppressive therapy (excluding cyclophosphamide) the dose must be stable for the 4 weeks prior to randomization and during the study (dose reductions for safety reasons will be permitted).
- •QTc(F)<450 msec or QTc(F)<480 msec for patients with bundle branch block.
- •Females of childbearing potential must use an acceptable method of birth control from randomization for at least 12 weeks after the last study drug administration.
排除标准
- •Diagnosed with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
- •Organ or life-threatening EGPA < 3 months prior to screening
- •Currently pregnant or breastfeeding, or planning to become pregnant during study participation.
- •Current malignancy or history of malignancy, unless received curative therapy >5 years ago, or >1 year ago for basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix
- •An untreated or refractory helminth parasitic infection < 24 weeks prior to screening
- •Unstable liver disease
- •Severe or clinically significant, uncontrolled cardiovascular disease
- •Other concurrent disease that may put the patient at risk, or may influence the results of the study, or the patients' ability to complete entire duration of the study
- •Chronic or ongoing infectious disease requiring systemic anti-infective treatment
- •Known immunodeficiency disorder or positive HIV test
- •Prior receipt of mepolizumab, reslizumab, dupilumab or benralizumab. Receipt of intravenous/intramuscular/subcutaneous corticosteroids within 4 weeks prior to randomization, receipt of omalizumab within 130 days prior to screening, rituximab within 6 months prior to screening (or B-cells not recovered), interferon-α or alemtuzumab within 6 months prior to screening, receipt of anti-tumor necrosis factor therapy within 12 weeks prior to screening or an investigational non-biologic product within 30 days or 5 half-lives prior to screening, whichever is longer. Receipt of any other marketed or investigational biologic products within 4 months or 5 half-lives prior to screening, whichever is longer.
研究组 & 干预措施
Benralizumab arm
Experimental
1x benralizumab SC injection + 3x placebo to mepolizumab SC injections
干预措施: Benralizumab (Biological)
Benralizumab arm
Experimental
1x benralizumab SC injection + 3x placebo to mepolizumab SC injections
干预措施: Placebo to Mepolizumab (Biological)
Mepolizumab arm
Active Comparator
3x mepolizumab SC injections + 1x placebo to benralizumab SC injection
干预措施: Mepolizumab (Biological)
Mepolizumab arm
Active Comparator
3x mepolizumab SC injections + 1x placebo to benralizumab SC injection
干预措施: Placebo to Benralizumab (Biological)
结局指标
主要结局
Number of Subjects Who Achieved Main Remission at Both Weeks 36 and 48
时间窗: Week 36 and Week 48
Percentage of patients with relapsing or refractory EGPA, achieving remission, defined as BVAS = 0 and OCS dose ≤ 4 mg/day (main remission definition) at both Weeks 36 and 48.
Supportive Endpoint: Proportion of Subjects Who Achieved Supportive Remission at Both Weeks 36 and 48
时间窗: Week 36 and Week 48
Supportive endpoint: Proportion of patients with relapsing or refractory EGPA, achieving remission, defined as BVAS = 0 and OCS dose ≤ 7.5 mg/day (supportive remission definition) at both Weeks 36 and 48.
次要结局
- Spirometry Change From Baseline by Timepoint up to Week 52: Pre-BD FVC (L)(from baseline to end of DB period, 52 Weeks)
- Total Accrued Duration of Remission During DB Treatment Period(from baseline to end of DB period, 52 Weeks.)
- Total Accrued Duration of Sustained Remission During DB Treatment Period(from baseline to end of DB period, 52 Weeks)
- Time From Randomization to First Eosinophilic Granulomatosis With Polyangiitis (EGPA) Relapse(from baseline to end of DB period, 52 Weeks)
- Annualized Eosinophilic Granulomatosis With Polyangiitis (EGPA) Relapse Rate(from baseline to end of DB period, 52 Weeks)
- Average Daily Dose of Prednisolone/Prednisone and Change From Baseline During Week 48 Through 52(last 4 weeks of DB period)
- Proportion of Patients With Average Daily Dose of Prednisolone/Prednisone During Week 48 Through 52(last 4 weeks of DB period)
- Percentage Reduction From Baseline in Average Daily Dose of Prednisolone/Prednisone During Week 48 Through 52(last 4 weeks of DB period)
- Proportion of Subjects With Reduction From Baseline in Average Daily Dose of Prednisolone/Prednisone During Week 48 Through 52(last 4 weeks of DB period)
- Proportion of Subjects Who Achieve Clinical Benefit(from baseline to end of DB period, 52 Weeks)
- Proportion of Patients Who Have Achieved Remission Within the First 24 Weeks and Remained in Remission for Remainder of the Double-blind Treatment Period(from baseline to end of DB period, 52 Weeks)
- Change From Baseline in Birmingham Vasculitis Activity Score (BVAS)(from baseline to end of DB period, 52 Weeks)
- Spirometry Change From Baseline by Timepoint up to Week 52: Pre-BD FEV1 (L)(from baseline to end of DB period, 52 Weeks)
- Change From Baseline in Vasculitis Damage Index (VDI)(from baseline to end of DB period, 52 Weeks)
- Change From Baseline in Asthma Control Questionnaire (6-item Version) (ACQ-6)(from baseline to end of DB period, 52 Weeks)
- Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) Component: Physical Component Summary (PCS)(from baseline to end of DB period, 52 Weeks)
- Change From Baseline in Short Form 36-item Health Survey (Version 2, Acute Recall) (SF-36v2) Component: Mental Component Summary (MCS)(from baseline to end of DB period, 52 Weeks)
- Change From Baseline in Sino-nasal Outcome Test-22 (SNOT-22) Total Score(from baseline to end of DB period, 52 Weeks)
- Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Runny Nose(from baseline to end of DB period, 52 Weeks)
- Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Post-nasal Discharge(from baseline to end of DB period, 52 Weeks)
- Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Facial Pain/Pressure(from baseline to end of DB period, 52 Weeks)
- Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Loss or Reduction in Sense of Taste/Smell(from baseline to end of DB period, 52 Weeks)
- Sino-nasal Symptoms Questionnaire (SSQ) Scores: Symptom Blockage/Congestion of Nose(from baseline to end of DB period, 52 Weeks)
- Patient Global Impression of Severity (PGIS) Category(from baseline to end of DB period, 52 Weeks)
- Patient Global Impression of Change (PGIC) Category(from baseline to week 4)
- WPAI-GH Endpoint, Change From Baseline by Timepoint: Absenteeism (%)(from baseline to end of DB period, 52 Weeks)
- WPAI-GH Endpoint, Change From Baseline by Timepoint up to Week 52: Subscale: Presenteeism (Impairment at Work) (%), Range 0-100.(from baseline to end of DB period, 52 Weeks)
- WPAI-GH Endpoint, Change From Baseline by Timepoint: Work Productivity Loss (%)(from baseline to end of DB period, 52 Weeks)
- WPAI-GH Endpoint, Change From Baseline by Timepoint: Activity Impairment (%)(from baseline to end of DB period, 52 Weeks)
- Absolute Eosinophil Count, Change From Baseline(from baseline to end of DB period, 52 Weeks)
研究者
研究点 (51)
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