A 12-week, Multicenter, Randomized, Double-blind, Parallel-arm, Placebo-controlled Study to Assess the Efficacy and Safety of CSJ117, When Added to Existing Asthma Therapy in Patients ≥ 18 Years of Age With Severe Uncontrolled Asthma.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 335
- 试验地点
- 1
- 主要终点
- Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12
研究概览
简要总结
The purpose of this study is to determine the efficacy and safety of multiple CSJ117 doses (0.5; 1; 2; 4 and 8 mg) inhaled once daily compared with placebo, when added to standard-of-care (SoC) asthma therapy in adult patients with uncontrolled asthma with respect to change from baseline in FEV1 at the end of 12 weeks of treatment.
详细描述
This was a randomized, multicenter, multi-national, double-blind, placebo-controlled, parallel-arm study evaluating the effect of 5 dose levels of CSJ117 in adult subjects with inadequately controlled asthma despite medium to high dose inhaled corticosteroid (ICS) plus long-acting beta agonist (LABA).
Subjects were assigned to one of the following six treatment arms/groups in a ratio of 2:1:1:1:2:2:
- Placebo inhaled once daily
- CSJ117 0.5 mg inhaled once daily
- CSJ117 1.0 mg inhaled once daily
- CSJ117 2.0 mg inhaled once daily
- CSJ117 4.0 mg inhaled once daily
- CSJ117 8.0 mg inhaled once daily
The study included:
- A screening period of approximately 2 weeks
- A single blinded placebo run-in period of 4 weeks (extended to 8 weeks for subjects experiencing an asthma exacerbation or respiratory tract infection during the run-in period)
- A double blinded treatment period of 12 weeks
- A follow-up period of up to 12 weeks, study drug free, following the last dose of study treatment.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed asthma
- •Male and female patients aged ≥18 and ≤75 years
- •Patients who have been treated with medium or high dose ICS plus LABA with up to 2 additional controllers
- •Morning pre-BD FEV1 value of ≥ 40% and ≤ 85% of the predicted normal
- •A positive reversibility test
- •ACQ-5 score of ≥ 1.5 at screening and end of run-in visits.
排除标准
- •Patients who have a cigarette smoking history of greater than 10 pack years or current smokers
- •Pregnant or nursing (lactating) women
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using specified methods of contraception during dosing of study drug and until 12 weeks after last study drug treatment
- •Patients with a history of immunodeficiency disease or hepatitis B, untreated and not cured hepatitis C or HIV.
研究组 & 干预措施
CSJ117 0.5mg
CSJ117 0.5 mg inhaled once daily
干预措施: CSJ117 (Drug)
CSJ117 0.5mg
CSJ117 0.5 mg inhaled once daily
干预措施: Placebo (Drug)
CSJ117 1mg
CSJ117 1 mg inhaled once daily
干预措施: CSJ117 (Drug)
CSJ117 1mg
CSJ117 1 mg inhaled once daily
干预措施: Placebo (Drug)
CSJ117 2mg
CSJ117 2 mg inhaled once daily
干预措施: CSJ117 (Drug)
CSJ117 2mg
CSJ117 2 mg inhaled once daily
干预措施: Placebo (Drug)
CSJ117 4mg
CSJ117 4 mg inhaled once daily
干预措施: CSJ117 (Drug)
CSJ117 4mg
CSJ117 4 mg inhaled once daily
干预措施: Placebo (Drug)
CSJ117 8mg
CSJ117 8 mg inhaled once daily
干预措施: CSJ117 (Drug)
CSJ117 8mg
CSJ117 8 mg inhaled once daily
干预措施: Placebo (Drug)
Placebo
Placebo inhaled once daily
干预措施: Placebo (Drug)
结局指标
主要结局
Average Change From Baseline in Pre-dose FEV1 at Week 8 and Week 12
时间窗: Baseline, Weeks 8-12
FEV1 (forced expiratory volume in one second) is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation, measured through spirometry testing. Pre-dose FEV1 is defined as average of the two FEV1 measurements taken at approximately 45 minutes and 15 minutes prior to dosing. The baseline pre-dose FEV1 value is defined as the average of the values taken approximately 2 hours 45 minutes and 2 hours 15 minutes prior to the first dose of double-blind treatment at Day 1. The least-squares means for change from baseline in pre-dose FEV1 averaged between Week 8 and Week 12 visits for each individual dose group were obtained from a linear mixed effects model for repeated measures (MMRM). A positive average change from baseline in pre-dose FEV1 is considered a favorable outcome.
次要结局
- Change From Baseline in Morning PEF at Week 12(Baseline, Week 12)
- Average Change From Baseline in AQLQ+12 Score at Week 8 and Week 12(Baseline, Weeks 8-12)
- Change From Baseline in ADSD Score at Week 8 and Week 12(Baseline, Week 8 and Week 12)
- Average Change From Baseline in FeNO at Week 8 and Week 12(Baseline, Weeks 8-12)
- CSJ117 Serum Concentration(Day 1 and Week 12: pre-dose, 2 and 4 hours post-dose; Weeks 2, 4 and 8: pre-dose and 4 hours post-dose; Weeks 14, 16, 20 and 24: pre-dose)
- Change From Baseline in Evening PEF at Week 12(Baseline, Week 12)
- Average Change From Baseline in ACQ-5 Score at Week 8 and Week 12(Baseline, Weeks 8-12)
- Change From Baseline in ANSD Score at Week 8 and Week 12(Baseline, Week 8 and Week 12)
- Change From Baseline in Number of Puffs of SABA Taken Per Day at Week 12(Baseline, Week 12)
- Number of Participants With On-treatment Adverse Events (AEs) and Serious Adverse Events (SAEs) During the On-treatment Period(From first dose of double-blind study treatment up to last dose (Week 12))
- Number of Participants With Anti-CSJ117 Antibodies(Day 1 and Weeks 2, 4, 8, 12, 14, 16, 20 and 24)