A Phase III, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy, Safety, and Tolerability of Lebrikizumab in Adolescent Patients With Uncontrolled Asthma Who Are On Inhaled Corticosteroids and a Second Controller Medication.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 346
- 试验地点
- 223
- 主要终点
- Percentage of Participants With Adverse Events (AEs) or Serious AEs
研究概览
简要总结
This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy, safety, and tolerability of lebrikizumab in adolescent participants with asthma whose disease remains uncontrolled despite daily treatment with inhaled corticosteroids (ICS) therapy and at least one second controller medication. Participants will be randomized in a 1:1:1 ratio to receive double-blind treatment with either lebrikizumab ('High' or 'Low') or placebo, administered as subcutaneous (SC) every 4 weeks (Q4W) for 52 weeks, in addition to their standard-of-care therapy. This will be followed by an optional 52-week double-blind active-treatment extension. The anticipated time on study treatment is up to 104 weeks. Participants who complete the study to Week 104, discontinue prematurely or decide not to take part in the optional active-treatment extension will transition to the 20-week safety follow-up period.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Asthma diagnosis for greater than or equal to (>/=) 12 months prior to Visit 1
- •Bronchodilator response during screening
- •Pre-bronchodilator FEV1 of 40 percent (%) - 90% predicted at both Visits 2 and 3
- •On high dose ICS therapy for >/= 6 months prior to Visit 1
- •On an eligible second controller medication for 6 months prior to Visit 1
- •Uncontrolled asthma as defined by the protocol both during screening and at the time of randomization
- •Demonstrated adherence with controller medication during the screening period
排除标准
- •History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
- •Maintenance oral corticosteroid therapy within 3 months prior to Visit 1
- •Treatment with systemic (oral, intravenous [IV], or intramuscular [IM]) corticosteroids within 4 weeks prior to Visit 1 or during the screening period
- •Treatment with intra-articular corticosteroids within 4 weeks prior to Visit 1 or during the screening period or anticipated need for intra-articular corticosteroids during the course of the study
- •Infection that meets the following criteria: Any infection requiring hospital admission or requiring treatment with IV or IM antibiotics within 4 weeks prior to Visit 1 or during screening; any active infection that required treatment with oral antibiotics within 2 weeks prior to Visit 1 or during screening; upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during screening; active parasitic infection or Listeria monocytogenes infection within 6 months prior to Visit 1 or during screening
- •History of active tuberculosis requiring treatment
- •Known immunodeficiency, including, but not limited to, human immunodeficiency virus (HIV) infection
- •Evidence of acute or chronic hepatitis or known liver cirrhosis
- •History of cystic fibrosis, bronchiectasis, and/or other clinically significant lung disease other than asthma
- •Diagnosis or history of malignancy or current evaluation for potential malignancy
- •Current smoker or former smoker with a history of greater than (>) 10 pack-years
- •History of alcohol or drug abuse
- •Past and/or current use of any anti- interleukin (IL) -13 or anti-IL-4/IL-13 therapy, including lebrikizumab
- •Use of other monoclonal antibody therapy, including omalizumab, within 6 months or 5 drug half-lives (whichever is longer) prior to Visit 1
- •Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening
- •History of bronchial thermoplasty
研究组 & 干预措施
Lebrikizumab High
Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 micrograms [mcg] of fluticasone propionate dry powder inhaler [DPI] or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (high dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.
干预措施: Lebrikizumab (Drug)
Lebrikizumab Low
Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (low dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.
干预措施: Lebrikizumab (Drug)
Placebo
Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab matching placebo Q4W for 52 weeks during placebo-controlled period and then SC injection of lebrikizumab at high or low dose will be administered from Weeks 52 to 76 or 104 to participants who are willing to take part in optional active-treatment extension period.
干预措施: Lebrikizumab (Drug)
Lebrikizumab High
Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 micrograms [mcg] of fluticasone propionate dry powder inhaler [DPI] or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (high dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.
干预措施: Standard of Care (Drug)
Lebrikizumab Low
Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab (low dose) Q4W for 52 weeks during placebo-controlled period and up to 76 weeks or 104 weeks for participants who will be willing to take part in optional active-treatment extension period.
干预措施: Standard of Care (Drug)
Placebo
Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab matching placebo Q4W for 52 weeks during placebo-controlled period and then SC injection of lebrikizumab at high or low dose will be administered from Weeks 52 to 76 or 104 to participants who are willing to take part in optional active-treatment extension period.
干预措施: Standard of Care (Drug)
Placebo
Participants with uncontrolled asthma on ICS therapy (total daily dose of 500-2000 mcg of fluticasone propionate DPI or equivalent) and a second controller medication, will receive SC injection of lebrikizumab matching placebo Q4W for 52 weeks during placebo-controlled period and then SC injection of lebrikizumab at high or low dose will be administered from Weeks 52 to 76 or 104 to participants who are willing to take part in optional active-treatment extension period.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events (AEs) or Serious AEs
时间窗: Baseline up to Week 124
Rate of Asthma Exacerbations During the 52-Week Placebo-Controlled Period
时间窗: Baseline up to Week 52
Percentage of Participants With Anti-Therapeutic Antibodies to Lebrikizumab
时间窗: Baseline up to Week 124 (assessed at Baseline, Weeks 4, 12, 24, 36, 52, 76, 104, 112, and 124 or at early termination [up to 108 weeks])
Rate of Asthma Exacerbations During 52-Week Placebo Controlled Period
时间窗: Baseline up to Week 52
An asthma exacerbation is defined as new or increased asthma symptoms (including wheeze, cough, dyspnea, chest tightness, and/or night-time awakening due to these symptoms) that lead to treatment with systemic corticosteroids or to hospitalization. Treatment with systemic corticosteroids is defined as treatment with oral, intravenous (IV), or intramuscular (IM) corticosteroids for at least 3 days or an emergency department visit with at least 1 dose of IV or IM corticosteroids. Rate of asthma exacerbation = total number of exacerbation events divided by total follow-up time in patient years.
次要结局
- Rate of Urgent Asthma-Related Health Care Utilization(Baseline up to 52 weeks)
- Injection Acceptability Questionnaire (IAQ) Score(Baseline up to Week 104)
- Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and Older (AQLQ + 12) at Week 52(Baseline, Week 52)
- Change From Baseline in Asthma Rescue Medication Use at Week 52(Baseline, Week 52)
- Change from Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 second (FEV1) at Week 52(Baseline , Week 52)
- Time to First Asthma Exacerbation(Baseline up to 52 weeks)
- Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52(Baseline , Week 52)
- Percent Change From Baseline in Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 52(Week 52)
- Absolute Change From Baseline in Pre-Bronchodilator FEV1 at Week 52(Week 52)
- Time to First Asthma Exacerbation(Baseline up to Week 52)
- Change From Baseline in Fractional Exhaled Nitric Oxide (FeNO) at Week 52(Week 52)
- Change From Baseline in Standardized Asthma Quality of Life Questionnaire for 12 Years and Older (AQLQ+12) Overall Score at Week 52(Week 52)
- Change From Baseline in Asthma Rescue Medication Use at Week 52(Week 52)
- Rate of Urgent Asthma-Related Health Care Utilization (HCU) Events(Baseline up to Week 52)
- Injection Acceptability Questionnaire (IAQ) Score(Baseline, Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48)
- Minimum Observed Serum Concentration (Ctrough) for Lebrikizumab(Predose (Hour 0) at Weeks 4, 12, 24, 36, and 52)