A Multicentre, Randomised, Double-Blind, Parallel-Group, Placebo-Controlled Phase 3 Efficacy and Safety Study of Benralizumab in Patients With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps (ORCHID)
概览
- 阶段
- 3 期
- 干预措施
- Benralizumab 30 mg
- 疾病 / 适应症
- 未指定
- 发起方
- AstraZeneca
- 入组人数
- 295
- 试验地点
- 116
- 主要终点
- Change From Baseline in Endoscopic Total Nasal Polyp Score (NPS) at Week 56
- 状态
- 终止
- 最后更新
- 2个月前
概览
简要总结
This is a randomized, double-blind, placebo-controlled, parallel-group, international, multicenter, Phase 3 study to evaluate the efficacy and safety of repeat dosing of benralizumab 30 mg administered subcutaneously (SC) versus placebo in patients with severe nasal polyposis.
详细描述
Approximately 250 patients will be randomized to receive benralizumab 30 mg SC or matching placebo. After enrolment, eligible patients will enter a 6-week screening/run in period. Patients who meet eligibility criteria will be randomised 1:1 at Week 0 (Day 0) to receive either placebo or benralizumab 30 mg SC every 4 weeks for the first 3 doses (Weeks 0, 4 and 8) and every 8 weeks thereafter (Weeks 16, 24, 32, 40 and 48). An end of treatment visit will be conducted at Week 56.All patients who complete the 56-week DB treatment period on investigational product (IP) may be eligible to continue into around one year OLE (Open Label Extension), during which all patients will receive 8 doses of benralizumab 30 mg. Patients in Benra arm during DB period will receive one dummy dose for the second dose during OLE (Open Label Extension). The last study visit will occur at 8 weeks after the last dose of IP (Week 112/FU). Patients who do not enter OLE (Open Label Extension), will have their last study visit at Week 56 (EoDB) for follow-up and without administration of IP.
研究者
入排标准
入选标准
- •Female or male patients aged 18 to 75 years inclusive
- •Stable Intranasal corticosteroids (INCS) use for at least 4 weeks prior to enrolment and throughout screening and DB period
- •History of treatment with systemic corticosteroids (SCS) or prior surgery for CRSwNP
- •Bilateral sinonasal polyposis with a nasal polyp score (NPS) of 5 at enrolment and randomization (unilateral score of at least 2 for each nostril)
- •Ongoing symptoms for at least 12 weeks prior to enrolment
- •Patient-reported moderate to severe nasal blockage score (NBS) ≥2 at enrolment
- •Bi-weekly mean NBS ≥ 1.5 at randomization
- •SNOT-22 total score ≥ 20 at enrolment and randomization
- •Documented physician-diagnosed asthma
- •Blood eosinophil count of \>2% or ≥150/μL at enrolment
排除标准
- •Any nasal and/or sinus surgery within 3 months prior to enrolment
- •Patients with conditions that makes them non evaluable for the co-primary efficacy endpoint including but not limited to:
- •Unilateral antrochoanal polyps
- •Nasal septal deviation that occludes at least one nostril
- •Current rhinitis medicamentosa
- •Allergic fungal rhinosinusitis or allergic fungal sinusitis;
- •Clinically important comorbidities (other eosinophil-driven diseases but CRSwNP) that may put the patient at risk, or may confound interpretation of clinical efficacy and/or safety results
- •Receipt of SCS for within 4 weeks prior to screening, or a scheduled SCS treatment during the study period.
- •Receipt of any marketed or investigational biologic product within 6 months of enrolment
- •Currently pregnant or breastfeeding
研究组 & 干预措施
Benralizumab
Benralizumab administered subcutaneously
干预措施: Benralizumab 30 mg
Placebo
Placebo administered subcutaneously
干预措施: Matched placebo
结局指标
主要结局
Change From Baseline in Endoscopic Total Nasal Polyp Score (NPS) at Week 56
时间窗: Baseline to Week 56
The total nasal polyp score (NPS) is the sum of the right and left nostril scores (maximum of 8), as evaluated by nasal endoscopy. Higher scores indicate greater symptom severity. The left and right score will be based on a central read with a scale from 0 to 4. Each nasal endoscopy is evaluated by two independent physician reviewers.
Change From Baseline in Mean Nasal Blockage Score (NBS) at Week 56.
时间窗: Baseline to week 56
The NBS is an item in the NPSD. Patients were asked to rate the severity of their worst nasal blockage over the past 24 hours using the following response options: 0 - none; 1 - mild; 2 - moderate; 3 - severe. Higher scores indicate greater symptom severity. The NBS and the changes from baseline were summarised every two weeks (bi-weekly). Baseline was the average of daily responses from Day -13 to Day 1. Bi-weekly mean were calculated if at least 8 days in each 14-day period had evaluable data; otherwise, the biweekly mean was set to missing.
次要结局
- Change From Baseline in Difficulty With Sense of Smell (DSS) Score at Week 56.(Baseline to Week 56)
- Sinus Opacification by CT Scan at Week 56.(Baseline to Week 56)
- Disease Specific Health-related Quality of Life (HRQoL): Change From Baseline in SinoNasal Outcome Test (SNOT-22) Score at Week 56.(Baseline to Week 56)
- Time to First Nasal Polyp Surgery(Baseline to Week 56)
- Time to First SCS Course for CRSwNP(Baseline to Week 56)
- Time to First NP Surgery and/or SCS Use for CRSwNP(Baseline to Week 56)
- Change From Baseline in Bi-weekly Mean Nasal Polyps Symptom Diary Total Symptom Score at Week 56.(Baseline to Week 56)
- Percentage of Participants With Surgery and/or Use SCS for CRSwNP(Baseline to Week 56)
- Percentage of Participants With Surgery for CRSwNP(Baseline to Week 56)
- Percentage of Participants With SCS Use for CRSwNP(Baseline to Week 56)