NCT02138916已完成3 期
Randomised, Double-blind, 56 Week Placebo-controlled, Parallel Group, Multicentre, Phase 3 Study to Evaluate the Efficacy and Safety of 2 Doses of Benralizumab in Patients With Moderate to Very Severe COPD With a History of Exacerbations
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 1,656
- 试验地点
- 1
- 主要终点
- Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL
研究概览
简要总结
The purpose of the study is to determine if benralizumab reduces COPD exacerbation rate in symptomatic patients with moderate to very severe COPD who are receiving standard of care therapies
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
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1.Informed consent. 2.Subjects 40-85 y.o. 3.Moderate to very severe COPD with Post Bronchodilator (BD) FEV1>20% and ≤65%. 4.≥2 moderate or ≥1 severe COPD exacerbation(s) required treatment or hospitalization within 2-52 weeks prior to Visit
- •Modified Medical Research Council (mMRC) score ≥1 at Visit
- •6.Treatment with double or triple therapy throughout the year prior to Visit 1, constant 2 weeks prior to Visit
- •7.Tobacco history of ≥10 pack-years. 8.Women of childbearing potential must use a highly effective form of birth control from Visit 1 until 16 weeks after their last dose, and negative serum pregnancy test result at Visit
- •9.Male subjects who are sexually active must be surgically sterile one year prior to Visit 1 or use an adequate method of contraception from the first Investigational Product (IP) dose until 16 weeks after their last dose. 10.Compliance with maintenance therapy during run-in ≥70%.
- •Blood eosinophils due to subject's stratification and cap for blood eosinophil levels.When any eosinophil cohort is full, subjects in the completed cohort will not be randomised and will be withdrawn from the study. Exclusion criteria:
- •Clinically important pulmonary disease other than COPD or another diagnosed pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
- •Any disorder or major physical impairment that is not stable by Investigator opinion and/or could affect: - subject safety-study findings or their interpretation or subject's ability to complete the entire study duration.
- •Unstable ischemic heart disease, arrhythmia, cardiomyopathy, or other relevant cardiovascular disorder that in Investigator's judgment may put the patient at risk or negatively affect the study outcome.
- •Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 2 weeks prior to Visit1 or during the enrolment and run-in period.
- •Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 2 weeks prior to Visit1or during the enrolment and run-in period.
- •Pneumonia within 8 weeks prior to Visit1 or during the enrolment and run-in period.
- •Pregnant, breastfeeding, or lactating women.
- •Risk factors for pneumonia
- •History of anaphylaxis to any other biologic therapy.
- •Long term oxygen therapy with signs and/or symptoms of cor pulmonale, right ventricular failure.
- •Use of immunosuppressive medication within 2 weeks prior to Visit1 and/or during the enrolment and run-in period.
- •Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to Visit
- •Evidence of active tuberculosis (TB) without an appropriate course of treatment.
- •Lung volume reduction surgery within the 6 months prior to Visit
- •History of partial or total lung resection (single lobe or segmentectomy is acceptable).
- •Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA) guidelines or other accepted guidelines.
- •Previous treatment with benralizumab.
- •Helminth parasitic infection diagnosed within 24 weeks prior to Visit 1.
排除标准
- 未提供
研究组 & 干预措施
Benralizumab Arm A
Experimental
Benralizumab administered subcutaneously
干预措施: Benralizumab Arm A (Drug)
Benralizumab Arm B
Experimental
Benralizumab administered subcutaneously
干预措施: Benralizumab Arm B (Drug)
Placebo
Placebo Comparator
Placebo administered subcutaneously
干预措施: Placebo (Drug)
结局指标
主要结局
Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL
时间窗: From first IP to week 56
A COPD exacerbation is defined by symptomatic worsening of COPD requiring: * Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or * Use of antibiotics; and/or * An inpatient hospitalization or death due to COPD Annual COPD exacerbation rate is the number of exacerbations per year. Its raw rate is calculated by number of exacerbations divided by the treatment period and then normalized to an annual rate, and is estimated by negative binomial model. Rate ratio between two treatment groups is also estimated through this model.
次要结局
- Annual COPD Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS<220/uL(From first IP to week 56)
- Mean Change From Baseline in Total Rescue Medication Use (Number of Puffs Per Day) for Patients With Baseline EOS>=220/uL(First IP up to Week 56)
- Mean Change From Baseline in Proportion of Nights Awakenings Due to Respiratory Symptoms for Patients With Baseline EOS>=220/uL(First IP up to Week 56)
- Mean Change From Baseline to Week 56 in Pre-bronchodilator FEV1 (L) Value for Patients With Baseline EOS>=220/uL(First IP up to end of treatment Week 56)
- Mean Change From Baseline in CAT Total Score for Patients With Baseline EOS>=220/uL(First IP up to Week 56)
- Mean Change From Baseline in E-RS: COPD Total Score for Patients With Baseline EOS>=220/uL(First IP up to Week 56)
- Mean Change From Baseline in SGRQ Total Score for Patients With Baseline EOS>=220/uL(First IP up to Week 56)
- Number of Participants by Number of COPD Exacerbations Based on EXACT-PRO for Patients With Baseline EOS>=220/uL(Immediately following first IP up to week 56)
- Number of Participants Having at Least 1 COPD Exacerbation for Patients With Baseline EOS>=220/uL(Immediately following first IP up to week 56)
- Severity of EXACT-PRO for Patients With Baseline EOS>=220/uL(Immediately following first IP up to week 56)
- Time to First COPD Exacerbation(Immediately following first IP up to week 56)
- Duration of EXACT-PRO for Patients With Baseline EOS>=220/uL(Immediately following first IP up to week 56)
- Annual EXACT-PRO Exacerbation Rate Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL(Immediately following first IP up to week 56)
- Annual COPD Exacerbation Rate Associated With ER or Hospitalization Over 56 Weeks Treatment Comparison for Patients With Baseline EOS>=220/uL(Immediately following first IP up to week 56)
- Number of Participants Had COPD-related Healthcare Encounter for Patient With Baseline EOS>=220/uL(Immediately following first IP up to week 56)
- Serum Concentration of Benralizumab(Pre-first dose and pre-dose at end of treatment (week 56))
- Immunogenicity of Benralizumab(Pre-treatment until end of follow-up, week 60 per protocol.)
- Duration of Study Treatment Administration(From first dose date to last dose date, 48 weeks per protocol.)
研究者
研究点 (1)
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