NCT05006573终止3 期
A Multicentre, Randomised, Double-blind, Parallel-group, Placebo-controlled, 52 Week, Phase III Study With an Open-label Extension to Evaluate the Efficacy and Safety of Benralizumab in Patients With Non-Cystic Fibrosis Bronchiectasis (MAHALE)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- AstraZeneca
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Annualized Bronchiectasis Exacerbations Rate in the Double-blind Period
研究概览
简要总结
This is a multicentre, randomised, double-blind, parallel-group, placebo-controlled, phase III study originally designed to test the hypothesis that benralizumab will reduce exacerbation rates compared with placebo on top of standard-of-care therapy in adult patients with non-cystic fibrosis bronchiectasis with eosinophilic inflammation (NCFB+EI).
All patients who complete the double-blind treatment period (28 to 52 weeks depending on the timing of patient randomization and when the revised CSP version 3.0 becomes effective) on investigational product (IP) may be eligible to continue into an open-label extension (OLE) period during which all patients will receive benralizumab.
The revised OLE period is intended to allow patients approximately 32 weeks of treatment with open label benralizumab (24 weeks followed by a FU visit 8 weeks after the last dose of IP for a total of approximately 32 weeks).
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, at least 18 years of age inclusive at the time of signing the ICF
- •Must have NCFB diagnosed by a physician and confirmed by CT (measured at screening; if a new CT is not possible, a CT performed within 12 months of the screening visit is acceptable).
- •Documented history of 2 or more bronchiectasis exacerbations within a year of the screening visit.
- •If receiving prophylactic systemic or inhaled antibiotics to prevent bronchiectasis exacerbations, the dose/regimen must be stable for at least 3 months prior to the screening visit and remain stable throughout the DB period of the study. If prophylactic macrolides have been recently discontinued, patients must have been off treatment for at least 3 months prior to randomisation. In all other cases of prophylactic antibiotic use, ≥ 4 weeks wash out period should be in place after the last dose of antibiotic and prior to randomisation
- •Must be on airway clearance therapy, physiotherapy, or mucus clearance therapy.The dose and regimen of these therapies and any drugs used to aid expectoration should be stable for at least 3 months prior to the screening visit and remain stable throughout the DB period of the study.
- •If receiving inhaled corticosteroid or bronchodilator therapy, the dose and regimen should be stable with no alteration to dose or formulation for at least 3 months prior to the screening visit and this should remain stable throughout the DB period of the study.
- •Women of childbearing potential (WOCBP) must have a negative serum and urine pregnancy test prior to randomization and agree to use a highly effective method of birth control from enrollment, throughout the study duration, and for 12 weeks after the last dose of IP.
排除标准
- •Pulmonary disease other than bronchiectasis. Patients with a history of NTM disease may be enrolled if they have completed treatment prior to the Screening visit, if at least 3 months have elapsed since the last day of antibiotic treatment for NTM at the Screening visit, and if they have had a negative sputum culture prior to the screening visit.
- •Another diagnosed or suspected pulmonary or systemic disease associated with elevated peripheral eosinophil counts
- •Respiratory infection or bronchiectasis exacerbation during the screening period.
- •Any other clinical condition that is not stable in the opinion of the Investigator and could:
- •Affect the safety of the patient during the study.
- •Influence the findings of the study or their interpretation.
- •Impede the patient's ability to complete the entire duration of the study.
- •Radiological findings suggestive of a respiratory disease other than bronchiectasis, suggestive of acute infection, or of solitary pulmonary nodules without appropriate follow up and demonstration of stability as per standard of care. Pulmonary nodules > 6 mm in size should have at least 2 years of follow up with no change on CT imaging.
- •Current active liver disease
- •Current malignancy, or history of malignancy, except for:
- •Patients who have had basal cell carcinoma, localised squamous cell carcinoma of the skin, or in situ carcinoma of the cervix are eligible provided the patient is in remission and curative therapy was completed at least 12 months prior to Visit 1
- •Patients who have had other malignancies are eligible provided that the participant is in remission and curative therapy was completed at least 5 years prior to Visit
- •History of known immunodeficiency disorder including a positive test for human immunodeficiency virus, HIV-1 or HIV-
- •History of alcohol or drug abuse within the past year
- •Current smokers with a tobacco history of ≥ 10 pack-years or ex-smoker with a tobacco history of ≥ 10 pack-years.
- •Patients receiving long-term oxygen treatment
- •Patients participating in, or scheduled for, an intensive (active) pulmonary rehabilitation programme. Patients who are in the maintenance phase of a rehabilitation programme are eligible.
- •Use of non-invasive positive-pressure ventilation for conditions other than obstructive sleep apnoea
- •Use of immunosuppressive medication within 3 months of the screening visit or expected need for chronic use (≥ 4 weeks) during study
- •Receipt of any marketed or investigational biologic products (monoclonal or polyclonal antibody) within one year of the screening visit
- •Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to randomisation
- •Receipt of immunoglobulin and blood products within 30 days of the date of the screening visit
- •Receipt of live attenuated vaccines within 30 days of the date of randomisation
- •Concurrent enrolment in another clinical drug interventional trial
- •History of anaphylaxis to any biologic therapy or vaccine
- •Known history of allergy or reaction to any component of the IP formulation.
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- •Judgement by the Investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements
- •Previous randomisation in the present study
- •Currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
研究组 & 干预措施
Benralizumab
Experimental
Benralizumab will be administered subcutaneously (SC) using an accessorized prefilled syringe (APFS)
干预措施: Benralizumab (Biological)
Placebo
Placebo Comparator
Matching placebo solution will be administered subcutaneously (SC) using an accessorized prefilled syringe (APFS)
干预措施: Placebo to Benralizumab (Biological)
结局指标
主要结局
Annualized Bronchiectasis Exacerbations Rate in the Double-blind Period
时间窗: through Double-blind period, at least 28 weeks and up to 52 weeks
Annualized Non-Cystic Fibrosis Bronchiectasis (NCFB) exacerbations rate through end of double-blind treatment period.
次要结局
- Time to First Exacerbation in the Double-blind Treatment Period(through Double-blind period, at least 28 weeks and up to 52 weeks)
- Change From Baseline in QoL-B-RSS Over the Double-blind Period(through Double-blind period, at least 28 weeks and up to 52 weeks)
- Change From Baseline in Pre-dose Pre-BD FEV1 Over the Double-blind Treatment Period(through Double-blind period, at least 28 weeks and up to 52 weeks)
- Change From Baseline in LCQ Total Score Over the Double-blind Period(through Double-blind period, at least 28 weeks and up to 52 weeks)
- Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Physical Functioning Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
- Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Role Functioning Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
- Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Emotional Functioning Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
- Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Social Functioning Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
- Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Vitality Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
- Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Health Perceptions Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
- Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Treatment Burden Scale(through Double-blind period, at least 28 weeks and up to 52 weeks)
- Change From Baseline in SGRQ Total Score Over the Double-blind Treatment Period(through Double-blind period, at least 28 weeks and up to 52 weeks)
研究者
研究点 (1)
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