Distribution of Eosinophils in Asthma After Reslizumab (DEAR). A 7-Week, Placebo-Controlled, Double-Blinded, Parallel-Group, Imaging Study Using Positron Emission Tomography/Computer Tomography (PET/CT) to Characterize the Effect of Intravenous Reslizumab on Airway Inflammation in Patients With Eosinophilic Asthma
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Part 1: Average Global Lung Glycolysis (GLG) at Baseline (Day 1)
研究概览
简要总结
This is an exploratory study with the following primary objectives: 1) to establish that PET/CT of the lung can reliably distinguish healthy, non-asthmatic participants from participants with severe asthma and an eosinophilic phenotype and 2) to examine the utility of PET/CT for demonstrating that reslizumab produces a reduction in lung inflammation in participants with severe asthma and an eosinophilic phenotype .
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 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male or female, 18 through 50 years of age.
- •Females that are either surgically sterile, are 2 years postmenopausal, or have a negative pregnancy test at screening.
- •Females of childbearing potential (not surgically sterile or 2 years postmenopausal), have to use a medically accepted method of contraception and have to agree to continue to use of this method for the duration of the study and for 5 months after study drug administration.
- •Participants with less that 10-pack year history of smoking.
- •Have a previous diagnosis of asthma.
- •Participants taking inhaled fluticasone at a dosage of at least 440 micrograms (mcg) daily, or equivalent.
- •The participant's baseline asthma therapy must be stable for 30 days prior to screening and judged by their treating physician to be able to continue without dosage changes throughout the study.
- •Participants with a blood eosinophil level of at least 400 cells/microliter (cells/μL) at screening. Participants with a blood eosinophil level below 400 cells/μL will be given 2 additional screening opportunities to determine blood eosinophil levels.
- •Additional criteria apply; please contact the investigator for more information.
排除标准
- •Participants requiring treatment with oral, intramuscular, or IV corticosteroids within 6 weeks of the Part 1 baseline visit for an asthma exacerbation.
- •Participants with any other confounding underlying lung disorder including but not limited to: bronchiectasis, chronic obstructive pulmonary disorder, smoking greater than or equal to (≥)10 pack year history, pulmonary fibrosis, emphysema, cystic fibrosis, and lung cancer.
- •Participants diagnosed with diabetes mellitus.
- •Participants with pulmonary conditions and blood eosinophilia other than eosinophilic asthma.
- •Participants with clinically meaningful comorbidity that can interfere with the study schedule or procedures, or compromise the participant's safety.
- •Participants that are current smokers (that is, have smoked within the last 12 months prior to screening).
- •Participants using systemic immunosuppressive, immunomodulating, or other biologic agents (including, but not limited to, anti-IgE mAb, methotrexate, cyclosporin, interferon-α, or anti-tumor necrosis factor mAb) within 6 months prior to screening. Participants whose treatment with anti-IgE mAb therapy (omalizumab) is considered ineffective by their physician may be included as potential participants when:
- •The omalizumab (Xolair) therapy has been discontinued.
- •The participant's blood eosinophil level meets inclusion criteria.
- •Participants who have previously received an anti-hIL-5 mAb (for example, reslizumab, mepolizumab [Nucala]) or anti-IL-5 receptor mAb (eg, benralizumab). Participants whose treatment with mepolizumab or benralizumab is considered ineffective by their physician may be included as potential participants when:
- •The mepolizumab or benralizumab therapy has been discontinued.
- •The participant's blood eosinophil level meets inclusion criteria.
- •Participants who had concurrent infection or disease that may preclude assessment of active asthma.
- •Participants with a history of concurrent immunodeficiency (human immunodeficiency virus or acquired immunodeficiency syndrome or congenital immunodeficiency).
- •Participants that had an active parasitic infection within 6 months prior to screening.
- •Participants with any disorder that may interfere with drug absorption, distribution, metabolism, or excretion (including gastrointestinal surgery).
- •Known hypersensitivity to study drug or to FDG/contrast agents
- •Treatment with metformin.
- •Compromised renal function.
- •Additional criteria apply; please contact the investigator for more information.
研究组 & 干预措施
Part 1: PET/CT Scan
Healthy participants will have 2 PET/CT scan in Part 1: within 7 days of eligibility being confirmed, and 7 days after the first PET/CT scan. Participants will receive Fluorodeoxyglucose F-18 (FDG) as part of the PET/CT procedures and will provide sputum/blood samples.
干预措施: Fludeoxyglucose F 18 (FDG) (Drug)
Part 2: Reslizumab
Reslizumab 3.0 milligrams/kilogram (mg/kg) will be administered by intravenous (IV) infusion, over 20 to 50 minutes, at Baseline (Day 1) of Part 2. PET/CT scan will be done on Weeks 2, 4 and 6. Participants will receive FDG as part of the PET/CT procedures and will provide sputum/blood samples.
干预措施: Reslizumab (Drug)
Part 2: Reslizumab
Reslizumab 3.0 milligrams/kilogram (mg/kg) will be administered by intravenous (IV) infusion, over 20 to 50 minutes, at Baseline (Day 1) of Part 2. PET/CT scan will be done on Weeks 2, 4 and 6. Participants will receive FDG as part of the PET/CT procedures and will provide sputum/blood samples.
干预措施: Fludeoxyglucose F 18 (FDG) (Drug)
Part 2: Placebo
Matching placebo will be administered by IV infusion at Baseline (Day 1) of Part 2. PET/CT scan will be done on Weeks 2, 4 and 6. Participants will receive FDG as part of the PET/CT procedures and will provide sputum/blood samples.
干预措施: Fludeoxyglucose F 18 (FDG) (Drug)
Part 2: Placebo
Matching placebo will be administered by IV infusion at Baseline (Day 1) of Part 2. PET/CT scan will be done on Weeks 2, 4 and 6. Participants will receive FDG as part of the PET/CT procedures and will provide sputum/blood samples.
干预措施: Placebo (Drug)
结局指标
主要结局
Part 1: Average Global Lung Glycolysis (GLG) at Baseline (Day 1)
时间窗: Baseline (Day 1) of Part 1
GLG is the total FDG uptake in the whole lung. A region of interest (ROI) was drawn around lung boundary in each axial slice. Standardized uptake value (SUV) mean and area of each ROI was recorded. Using the formula: area\*slice thickness the volume of each slice was calculated. Then the SUVmean of each slice was multiplied by the volume of the corresponding slice, which represented the total FDG uptake in one slice. This number for each slice was summed together to provide GLG of that lung. Average between GLG of right lung and GLG of left lung was reported.
Part 1: Average Global Lung Glycolysis (GLG) at Day 8
时间窗: Day 8
GLG is the total FDG uptake in the whole lung. ROI was drawn around lung boundary in each axial slice. SUV mean and area of each ROI was recorded. Using the formula: area\*slice thickness the volume of each slice was calculated. Then the SUVmean of each slice was multiplied by the volume of the corresponding slice, which represented the total FDG uptake in one slice. This number for each slice was summed together to provide GLG of that lung. Average between GLG of right lung and GLG of left lung was reported.
Part 2: Change From Baseline to Week 4 in GLG
时间窗: Baseline, Week 4
Part 2: Change From Baseline to Week 4 in Lung Parenchyma (LP) SUV Mean
时间窗: Baseline, Week 4
次要结局
- Part 2: Change From Baseline to Week 4 in Blood Eosinophil Counts(Baseline, Week 4)
- Change From Baseline to Week 4 in Forced Expiratory Volume in 1 Second (FEV1)(Baseline, Week 4)
- Change From Baseline to Week 4 in Fractional Exhaled Nitric Oxide (FeNO)(Baseline, Week 4)
- Change From Baseline to Week 4 in Asthma Quality of Life Questionnaire (AQLQ) Score(Baseline, Week 4)
- Number of Participants With Adverse Events (AEs)(21 days)