A 12-Month, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Reslizumab (3.0 mg/kg) in the Reduction of Clinical Asthma Exacerbations in Patients (12-75 Years of Age) With Eosinophilic Asthma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 464
- 试验地点
- 104
- 主要终点
- Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment
研究概览
简要总结
The primary objective of this study is to determine whether reslizumab is more effective than placebo in reducing the number of clinical asthma exacerbations (CAEs) in patients with eosinophilic asthma.
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
- 12 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient is male or female, 12 through 75 years of age, with a previous diagnosis of asthma. Patients 12 through 17 years of age are excluded from participating in Germany, India, Argentina, and Korea; patients 66 through 75 years of age are excluded from participating in India and Korea.
- •The patient has had at least 1 asthma exacerbation requiring oral, intramuscular (im), or intravenous (iv) corticosteroid use for at least 3 days over the past 12 months before screening.
- •The patient has a current blood eosinophil level of at least 400/μL.
- •The patient has airway reversibility of at least 12% to beta-agonist administration.
- •The patient has an ACQ score of at least 1.5 5 at the screening and baseline (before the 1st dose of study drug) visits.
- •The patient is taking inhaled fluticasone at a dosage of at least 440 μg, or equivalent, daily. Chronic oral corticosteroid use (no more than 10 mg/day prednisone or equivalent) is allowed. If a patient is on a stable dose, eg, 2 weeks or more of oral corticosteroid treatment at the time of study enrollment, the patient must remain on this dose throughout the study. The patient's baseline asthma therapy regimen (including, but not limited to, inhaled corticosteroids, oral corticosteroids up to a maximum dose of 10 mg prednisone daily or equivalent, leukotriene antagonists, 5-lipoxygenase inhibitors, or cromolyn) must be stable for 30 days prior to screening and baseline and must continue without dosage changes throughout the study.
- •All female patients must be surgically sterile, 2 years postmenopausal, or must have a negative pregnancy test (ß-human chorionic gonadotropin [ß-HCG]) at screening (serum) and baseline (urine).
- •Female patients of childbearing potential (not surgically sterile or 2 years postmenopausal), must use a medically accepted method of contraception and must agree to continue use of this method for the duration of the study and for 30 days after participation in the study. Acceptable methods of contraception include barrier method with spermicide, abstinence, intrauterine device (IUD), or steroidal contraceptive (oral, transdermal, implanted, and injected). NOTE: Partner sterility alone is not acceptable for inclusion in the study.
- •Written informed consent is obtained. Patients 12 through 17 years old, where participating, must provide assent.
- •The patient is in reasonable health (except for diagnosis of asthma) as judged by the investigator, and as determined by a medical history, medical examination, ECG evaluation (at screening), serum chemistry, hematology, and urinalysis.
- •The patient must be willing and able to understand and comply with study restrictions, requirements, and procedures, as specified by the study center, and to remain at the study center for the required duration during the study period, and willing to return to the study center for the follow-up evaluation as specified in this protocol.
- •Patients who experience an asthma exacerbation during the screening period will be considered to have failed screening and cannot be randomly assigned to study drug. Patients may be rescreened 1 time only.
排除标准
- •The patient has a clinically meaningful co-morbidity that would interfere with the study schedule or procedures, or compromise the patient's safety.
- •The patient has known hypereosinophilic syndrome.
- •The patient has another confounding underlying lung disorder (eg, chronic obstructive pulmonary disease, pulmonary fibrosis, or lung cancer). Patients with pulmonary conditions with symptoms of asthma and blood eosinophilia (eg, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis) will also be excluded.
- •The patient is a current smoker (ie, has smoked within the last 6 months prior to screening).
- •The patient is using systemic immunosuppressive, immunomodulating, or other biologic agents (including, but not limited to, anti-immunoglobulin E (IgE) mAb, methotrexate, cyclosporin, interferon-α, or anti-tumor necrosis factor [anti-TNF] mAb) within 6 months prior to screening.
- •The patient has previously received an anti-hIL-5 monoclonal antibody (eg, reslizumab, mepolizumab, or benralizumab).
- •The patient has any aggravating medical factors that are inadequately controlled (eg, rhinitis, gastroesophageal reflux disease, and uncontrolled diabetes).
- •The patient has participated in any investigative drug or device study within 30 days prior to screening.
- •The patient has participated in any investigative biologics study within 6 months prior to screening.
- •Other exclusion criteria apply.
研究组 & 干预措施
Placebo
Placebo administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
干预措施: Placebo (Drug)
Reslizumab 3.0 mg/kg
Reslizumab 3.0 mg/kg administered intravenously once every 4 weeks ( +-7 days) for a total of 13 doses.
干预措施: Reslizumab (Drug)
结局指标
主要结局
Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment
时间窗: Day 1 to Month 12
An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization. CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals were based on Negative Binomial regression model adjusted for stratification factors. Results are offered as adjusted means.
Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs)
时间窗: Day 1 to Month 12
An exacerbation event was considered a CAE if the patient met either or both of the criteria listed below and this was corroborated with at least 1 other measurement to indicate the worsening of clinical signs and symptoms of asthma: * use of systemic, or an increase in the use of inhaled, corticosteroid treatment for 3 or more days; or an increased 2 or more fold for at least 3 or more days for patient's already on corticosteroids. * asthma-related emergency treatment, such as an unscheduled visit to the physician's office or emergency room for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms, or an asthma-related hospitalization CAEs were adjudicated by committee to assure consistency. Adjusted CAE rate and confidence intervals for the two criteria were based on Negative Binomial regression model adjusted for stratification factors. Results are offered as adjusted means.
次要结局
- Change From Baseline in Asthma Control Questionnaire (ACQ) Over 16 Weeks Using Mixed Model for Repeated Measures(Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16)
- Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) Over 16 Weeks Using Mixed Model for Repeated Measures(Day 1 (baseline, pre-dose), Weeks 4, 8, 12 and 16)
- Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE)(Day 1 to Day 526 (longest treatment time plus 2 weeks))
- Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values(Week 4 to Week 52)
- Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1) At Week 16(Day 1 (baseline, pre-dose), Week 16)
- Participants With Treatment-Emergent Adverse Events TEAE)(Day 1 (post-dose) to Week 65. The endpoint for adverse events was the last postbaseline observation, which included the 90 day follow-up visit.)
- Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16(Day 1 (baseline, pre-dose), Week 16)
- Change From Baseline in Asthma Symptom Utility Index (ASUI) Over 16 Weeks Using Mixed Model for Repeated Measures(Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16)
- Change From Baseline in Blood Eosinophil Count Over 16 Weeks and 52 Weeks Using Mixed Model for Repeated Measures(Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 or early withdrawal)
- Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values(Week 4 to Week 52)
- Participants With a Positive Anti-Reslizumab Antibody Status During Study(Baseline visit (prior to reslizumab exposure), Weeks 16, 32, 48 and 52)
- Change From Baseline in Short-Acting Beta-Agonist (SABA) Use Over 16 Weeks Using Mixed Model for Repeated Measures(Day 1 (baseline, pre-dose), Weeks 4, 8, 12, 16)