A Randomized, Double-Blind, Placebo-Controlled Dose-Ranging Biomarker Study of the Effects of Dexpramipexole on Eosinophils in Subjects With Eosinophilic Asthma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 534
- 试验地点
- 2
- 主要终点
- Change in Blood Absolute Eosinophil Count From Baseline to Week 12
研究概览
简要总结
This is a randomized, double-blind, placebo-controlled, parallel-group, dose-ranging, multi-center study to evaluate the clinical effects of oral administration of dexpramipexole for 12 weeks on peripheral blood eosinophil count in subjects with eosinophilic asthma.
详细描述
One hundred subjects will receive study drug or matching placebo over 12 weeks of consecutive dosing. Following a short Run-in Period, eligible subjects will enter the Primary Assessment Period and receive twice-daily dosing of study drug or placebo for 12 weeks. Following 12 weeks of treatment, subjects will enter a 12-week Eosinophil Recovery Period. The primary endpoint for the study is the change in blood absolute eosinophil count from Baseline to Week 12.
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 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female ≥18 and <75 years of age at the time of consent
- •Physician diagnosis of asthma for ≥12 months (relative to Baseline) based on Global Initiative for Asthma (GINA) 2018 Guidelines
- •Asthma requiring treatment with, at a minimum, low dose inhaled corticosteroids in combination with a long-acting β2 agonist, on a stable dose for at least 1 month before Screening
- •Bronchodilator reversibility, as evidenced by ≥12% and ≥200 mL improvement in FEV1 15 to 25 minutes following inhalation of albuterol at Screening
- •Pre-bronchodilator FEV1 ≥40% and <80% of predicted at Screening and Baseline
- •AEC ≥0.30 x10^9/L at the Screening visit
- •ACQ-7 ≥1.5 at Screening
- •Negative pregnancy test at Baseline
- •Adherence ≥85% with twice-daily placebo taken during the Run-in Period
排除标准
- •Treatment for an asthma exacerbation within 8 weeks prior to Baseline visit
- •Treatment with systemic corticosteroids in the 8 weeks prior to Screening
- •Treatment with monoclonal antibody therapy, within 5-half-lives prior to Baseline
- •Treatment with selected drugs known to have a substantial risk of neutropenia
- •Absolute neutrophil count <2.0x10^9/L at Screening, or any documented history of absolute neutrophil count <2.0x10^9/L.
- •Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m^2 at Screening
- •Clinically significant abnormal laboratory or ECG values
- •Other medically significant illness
- •Use of any smoke or inhaled nicotine delivery device within 1 year prior to Screening
- •Pregnant women or women breastfeeding
- •Currently taking pramipexole or other dopamine agonists
研究组 & 干预措施
placebo BID
Following a 2-4 week placebo run-in, randomized subjects received 1 tablet placebo twice daily for 12 weeks.
干预措施: Placebo (Drug)
37.5 mg BID dexpramipexole
Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 37.5 mg dexpramipexole twice daily for 12 weeks.
干预措施: Dexpramipexole (Drug)
75 mg BID dexpramipexole
Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 75 mg dexpramipexole twice daily for 12 weeks.
干预措施: Dexpramipexole (Drug)
150 mg BID dexpramipexole
Following a 2-4 week placebo run-in, randomized subjects received 1 tablet of 150 mg dexpramipexole twice daily for 12 weeks.
干预措施: Dexpramipexole (Drug)
结局指标
主要结局
Change in Blood Absolute Eosinophil Count From Baseline to Week 12
时间窗: Baseline, 12 Weeks
The primary endpoint of this study was the change in AEC from Baseline to Week 12 on a ratio scale. The analysis used a mixed effects model repeated-measures (MMRM) with terms for log10 transformed baseline, GINA treatment step, treatment, visit, treatment by visit interaction, and log10 transformed baseline by visit interaction as fixed effects, and subject as a random effect. An unstructured covariance matrix was used. The response variable was the log10 transformed post-baseline value minus the log10 transformed baseline value. The estimates of Geometric LS Means and their ratios were obtained by back transforming the corresponding estimates of LS means and their differences to the original scale.
次要结局
- Change in Pre-bronchodilator FEV1 (Liters) From Baseline to Week 12(Baseline, 12 Weeks)
- Change in Asthma Control Questionnaire (ACQ-6) Score From Baseline to Week 12(Baseline, 12 Weeks)
- Change in Post-bronchodilator FEV1 From Baseline to Week 12(Baseline, 12 Weeks)
- Number of Participants With Potentially Clinically Significant Hematology Results by Treatment Group Post Randomization Through Week 12(Immediately post-baseline up to Week 12)
- Number of Participants With Potentially Clinically Significant Urinalysis Results by Treatment Group Post Randomization Through Week 12(Immediately post-baseline up to Week 12)
- Number of Participants With Potentially Clinically Significant Vital Signs Results by Treatment Group Post Randomization Through Week 12(Immediately post-baseline up to Week 12)
- Number of Participants With Potentially Clinically Significant ECG Results by Treatment Group Post Randomization Through Week 12(Immediately post-baseline up to Week 12)
- Change in Quality of Life, as Measured by the Asthma Quality of Life Questionnaire (AQLQ) From Baseline to Week 12(Baseline, 12 Weeks)
- Number of Participants With Potentially Clinically Significant Blood Chemistry Results by Treatment Group Post Randomization Through Week 12(Immediately post-baseline up to Week 12)