A Phase II, Randomized, Double-Blind, Placebo-Controlled, Study to Assess the Efficacy and Safety of Lebrikizumab in Patients With Idiopathic Pulmonary Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 505
- 试验地点
- 112
- 主要终点
- Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks
研究概览
简要总结
This randomized, multicenter, double-blind, placebo-controlled, parallel-group study will evaluate the efficacy and safety of lebrikizumab as monotherapy in the absence of background IPF therapy and as combination therapy with pirfenidone background therapy in participants with IPF. Participants will be randomized to receive either lebrikizumab or placebo subcutaneously every 4 weeks.
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
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a diagnosis of IPF within the previous 5 years from time of screening and confirmed at baseline
- •FVC >/=40 percent (%) and </=100% of predicted at screening
- •Stable baseline lung function as evidenced by a difference of less than (<) 10% in FVC (in liters) measurements between screening and Day 1, Visit 2 prior to randomization
- •DLco >/=25% and </=90% of predicted at screening
- •Ability to walk >/=100 meters unassisted in 6 minutes
- •Cohort A: No background IPF therapy for >/=4 weeks allowed prior to randomization and throughout the placebo-controlled study period
- •Cohort B: Tolerated dose of pirfenidone </=2403 milligrams once daily (mg/day) for >/=4 weeks required prior to randomization and throughout the placebo-controlled study 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
- •Evidence of other known causes of interstitial lung disease
- •Lung transplant expected within 12 months of screening
- •Evidence of clinically significant lung disease other than IPF
- •Post-bronchodilator forced expiratory volume in 1 second (FEV1)/FVC ratio <0.7 at screening
- •Positive bronchodilator response, evidenced by an increase of >/=12% predicted and 200 milliliters increase in FEV1 or FVC
- •Class IV New York Heart Association chronic heart failure or historical evidence of left ventricular ejection fraction <35%
- •Hospitalization due to an exacerbation of IPF within 4 weeks prior to or during screening
- •Known current malignancy or current evaluation for potential malignancy
- •Listeria monocytogenes infection or active parasitic infection within 6 months prior to Day 1, Visit 2
- •Active tuberculosis requiring treatment within 12 months of screening
- •Known immunodeficiency, including but not limited to human immunodeficiency virus infection
- •Past use of any anti-interleukin (IL)-13 or anti-IL-4/IL-13 therapy, including lebrikizumab
- •Evidence of acute or chronic hepatitis or known liver cirrhosis
- •Exclusions Criteria Limited to Cohort B:
- •Known achalasia, esophageal stricture, or esophageal dysfunction sufficient to limit the ability to swallow oral medication
- •Tobacco smoking or use of tobacco-related products within 3 months of screening or unwillingness to avoid smoking throughout the study period
- •Known or suspected peptic ulcer
- •Any condition that, as assessed by the investigator, might be significantly exacerbated by the known side effects associated with pirfenidone
- •Creatinine clearance <40 milliliters/minute, calculated using the Cockcroft-Gault formula
- •Use of following therapies within 4 weeks of randomization (Day 1, Visit 2) or during the study: Strong inhibitors of CYP1A2 (Cytochrome P450 Family 1 Subfamily A Member 2) (example: fluvoxamine or enoxacin); Moderate inducers of CYP1A2 (limited to tobacco smoking and tobacco-related products)
研究组 & 干预措施
Monotherapy (Cohort A): Placebo
Participants will receive monotherapy with placebo matched to lebrikizumab administered via subcutaneous (SC) injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period. Participants will be allowed to receive treatment with lebrikizumab at a dose of 250 mg administered via SC injection once every 4 weeks up to additional 52 weeks (that is, up to Week 104) in the open-label period.
干预措施: Lebrikizumab (Drug)
Monotherapy (Cohort A): Placebo
Participants will receive monotherapy with placebo matched to lebrikizumab administered via subcutaneous (SC) injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period. Participants will be allowed to receive treatment with lebrikizumab at a dose of 250 mg administered via SC injection once every 4 weeks up to additional 52 weeks (that is, up to Week 104) in the open-label period.
干预措施: Placebo (Drug)
Monotherapy (Cohort A): Lebrikizumab
Participants will receive monotherapy with lebrikizumab at a dose of 250 milligrams (mg) administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period. Participants will be allowed to receive treatment with lebrikizumab at a dose of 250 mg administered via SC injection once every 4 weeks up to additional 52 weeks (that is, up to Week 104) in the open-label period.
干预措施: Lebrikizumab (Drug)
Combination Therapy (Cohort B): Placebo + Pirfenidone
Participants will receive pirfenidone at a stable dose of 2403 mg per day (three 267 mg capsules three times a day [9 capsules daily] for a total of 2403 mg/day) or at maximum tolerated dose (MTD) administered orally along with placebo matched to lebrikizumab administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period.
干预措施: Pirfenidone (Drug)
Combination Therapy (Cohort B): Placebo + Pirfenidone
Participants will receive pirfenidone at a stable dose of 2403 mg per day (three 267 mg capsules three times a day [9 capsules daily] for a total of 2403 mg/day) or at maximum tolerated dose (MTD) administered orally along with placebo matched to lebrikizumab administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period.
干预措施: Placebo (Drug)
Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Participants will receive pirfenidone at a stable dose of 2403 mg per day (three 267 mg capsules three times a day [9 capsules daily] for a total of 2403 mg/day) or at MTD administered orally along with lebrikizumab at a dose of 250 mg administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period.
干预措施: Lebrikizumab (Drug)
Combination Therapy (Cohort B): Lebrikizumab + Pirfenidone
Participants will receive pirfenidone at a stable dose of 2403 mg per day (three 267 mg capsules three times a day [9 capsules daily] for a total of 2403 mg/day) or at MTD administered orally along with lebrikizumab at a dose of 250 mg administered via SC injection once every 4 weeks up to 52 weeks during the placebo-controlled treatment period.
干预措施: Pirfenidone (Drug)
结局指标
主要结局
Annualized Rate of Decrease in Percent Predicted Forced Vital Capacity (FVC) Over 52 Weeks
时间窗: Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52)
Annualized rates of decrease (slope throughout time from baseline to Week 52) for percent predicted FVC was assessed and reported. FVC is a standard pulmonary function test. FVC is defined as the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Predicted FVC is based on sex, age, and height of a person. Percent predicted FVC (in %) = \[(observed FVC)/(predicted FVC)\]\*100.
次要结局
- Annualized Rate of Decline in 6-Minute Walk Test (6MWT) Distance Over 52 Weeks(Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52))
- Annualized Rate of Decrease in FVC Over 52 Weeks(Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52))
- Progression-Free Survival (PFS)(Baseline up to the event of death from any cause, all cause hospitalization, or a decrease from baseline of >/=10% in FVC, whichever occurred first (up to Week 122))
- Time to First Occurrence of SGRQ Total Score Worsening or Death From Any Cause(Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122))
- Percentage of Participants With Event of Greater Than or Equal to (>/=) 10% Absolute Decline in Percent Predicted FVC or Death From Any Cause(Baseline up to the event of >/=10% absolute decline in percent predicted FVC or death from any cause, whichever occurred first (up to Week 122))
- Time to First Occurrence of a >/=10% Absolute Decline in Percent Predicted FVC or Death From Any Cause(Baseline up to the event of >/=10% absolute decline in percent predicted FVC or death from any cause, whichever occurred first (up to Week 122))
- Annualized Rate of Decrease in Diffusion Capacity of the Lung for Carbon Monoxide (DLco) Over 52 Weeks(Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52))
- Minimum Observed Serum Concentration (Cmin) of Lebrikizumab at Week 52(Predose (Hour 0) at Week 52)
- Elimination Half-Life (t1/2) of Lebrikizumab(Pre-dose (Hour 0) at Weeks 1, 4, 12, 24, 36, 64, 76, 88, 104; and at 4, 12, and 18 weeks post-last dose (last dose = Week 104))
- Percentage of Participants With Event of Death, All Cause Hospitalization, or a Decrease From Baseline of >/=10% in FVC(Baseline up to the event of death from any cause, all cause hospitalization, or a decrease from baseline of >/=10% in FVC, whichever occurred first (up to Week 122))
- Annualized Rate of Decrease in A Tool to Assess Quality of Life in IPF (ATAQ-IPF) Questionnaire Total Score Over 52 Weeks(Baseline up to Week 52 (assessed at Baseline, Weeks 1, 4, 12, 24, 36, 44, and 52))
- Percentage of Participants With an Event of Acute Idiopathic Pulmonary Fibrosis (IPF) Exacerbation(Baseline up to the event of acute IPF exacerbation (up to Week 122))
- Percentage of Participants With Respiratory-Related Hospitalization(Baseline up to the event of respiratory-related hospitalization (up to Week 122))
- Percentage of Participants With an Event of St. George's Respiratory Questionnaire (SGRQ) Total Score Worsening or Death From Any Cause(Baseline up to the event of SGRQ total score worsening or death from any cause, whichever occurred first (up to Week 122))
- Time to First Event of Acute IPF Exacerbation(Baseline up to the event of acute IPF exacerbation (up to Week 122))
- Time to Respiratory-Related Hospitalization(Baseline up to the event of respiratory-related hospitalization (up to Week 122))
- Percentage of Participants With Anti-therapeutic Antibody (ATA) to Lebrikizumab(Baseline and Post-Baseline (assessed at multiple time points: Weeks 4, 12, 24, 36, 52, 56, 64, 76, and at safety follow-up up to Week 122))
- Percentage of Participants With an Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause(Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122))
- Time to First Event of >/=15% Absolute Decrease in Percentage of Predicted DLco or Death From Any Cause(Baseline up to the event of >/=15% absolute decrease in percentage of predicted DLco or death from any cause (up to Week 122))
- Minimum Observed Serum Concentration (Cmin) of Lebrikizumab(Predose (Hour 0) at Weeks 4, 12, 24, and 36)