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
- 489
- 试验地点
- 128
- 主要终点
- Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment
研究概览
简要总结
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy, safety, and immunogenicity of treatment with reslizumab in patients with eosinophilic asthma.
详细描述
Demonstrate the efficacy of reslizumab, at a dose of 3 mg/kg administered iv every 4 weeks over 12 months, as assessed by the reduction in frequency of clinical asthma exacerbations (CAEs) during 12 months.
An exacerbation event will be considered a CAE if the patient meets either or both of the criteria listed below and this is 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
- asthma-related emergency treatment The above criteria must be corroborated with at least 1 other measurement to indicate worsening in the clinical signs and symptoms of 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.
- •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 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 of 10 mg of prednisone daily or equivalent, leukotriene antagonists, 5-lipooxygenase inhibitors, or cromolyn) must be stable for 30 days prior to screening and baseline, and must continue without dosage changes throughout 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.
- •Written informed consent is obtained. Patients 12 through 17 years old 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.
- •Other criteria apply; please contact the investigator for more information.
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 or immunomodulating or other biologic agents (including, but not limited to, anti-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.
- •Female patients who are pregnant, nursing, or, if of childbearing potential, and not using a medically accepted, effective method of birth control (eg, barrier method with spermicide, abstinence, IUD, or steroidal contraceptive [oral, transdermal, implanted, and injected]) are excluded from this study. NOTE: Partner sterility alone is not considered an acceptable form of birth control.
- •Other criteria apply; please contact the investigator for more information.
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 Week 52
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 Week 52
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 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 a Positive Anti-Reslizumab Antibody Status During Study(Weeks 16, 32, 48 and 52)
- 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)
- 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)
- Participants With Treatment-Emergent Adverse Events(Day 1 (post-dose) to Week 65. The last postbaseline value for approximately 20 patients in each)
- Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) to Week 16(Day 1 (baseline, pre-dose), Week 16)
- Kaplan-Meier Estimates for Time to First Clinical Asthma Exacerbation (CAE)(Day 1 to Day 478 (longest treatment time plus 2 weeks))
- 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 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)
- Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Abnormal Lab Values(Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each)
- Participants With Treatment-Emergent Potentially Clinically Significant (PCS) Vital Signs Values(Week 4 to Week 65. The last postbaseline value for approximately 20 patients in each)