Zephyrus II: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Pamrevlumab in Subjects With Idiopathic Pulmonary Fibrosis (IPF)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- FibroGen
- 入组人数
- 372
- 试验地点
- 157
- 主要终点
- DB Period: Change From Baseline in FVC at Week 48
研究概览
简要总结
This is a Phase 3 trial to evaluate the efficacy and safety of 30 milligrams (mg)/kilogram (kg) intravenous (IV) infusions of pamrevlumab administered every 3 weeks as compared to placebo in participants with Idiopathic Pulmonary Fibrosis (IPF). There is a 48-week randomized treatment phase followed by an optional, open-label extension phase.
详细描述
The intent of this study is to evaluate the efficacy and safety of pamrevlumab as monotherapy in participants with IPF. Participants who are not being treated with approved IPF therapies (that is, nintedanib or pirfenidone) may be eligible for screening. Examples of reasons participants may not be treated with approved IPF therapies include but are not limited to:
- Intolerant or not responsive to approved IPF therapies
- Ineligible to receive these therapies
- Participant voluntarily declines to receive approved IPF therapies after being fully informed of the potential benefits/risks
NOTE: No participant should discontinue an approved IPF therapy for the purpose of enrolling in this study.
During the 48-week treatment phase of the study, co-administration of an approved IPF therapy (such as, pirfenidone or nintedanib) is acceptable if clinically indicated in the Investigator's opinion, after assessment of potential risks/benefits of such combination with blinded study treatment.
Participants who complete the 48-week study will be eligible for an optional, open-label extension phase with continued access to pamrevlumab, regardless of their randomized assignment.
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)
盲法说明
During the Open-label extension phase, all participants will receive pamrevlumab in an open-label manner. No unblinding of participant's treatment assignment in the treatment phase (main study) will occur for purposes of open-label extension participation.
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of IPF as defined by American Thoracic Society/European Respiratory Society/Japanese Respiratory Society/Latin American Thoracic Association (ATS/ERS/JRS/ALAT) guidelines within the past 7 years prior to study participation.
- •High-resolution computed tomography (HRCT) scan at Screening, with ≥10% to <50% parenchymal fibrosis (reticulation) and <25% honeycombing.
- •FVCpp value >45% and <95% at Screening and Day 1 (prior to randomization).
- •Diffusing capacity of the lungs for carbon monoxide (DLCO) percent predicted ≥25% and ≤90%.
- •Not currently receiving treatment for IPF with an approved therapy for IPF (such as, pirfenidone or nintedanib) for any reason, including prior intolerance or lack of response to an approved IPF therapy, or choice to forego treatment with an approved IPF therapy after a full discussion with the Investigator regarding risks/benefits of such therapy.
排除标准
- •Previous exposure to pamrevlumab.
- •Evidence of significant obstructive lung disease, as evidenced by spirometry or HRCT.
- •Female participants who are pregnant or nursing.
- •Smoking within 3 months of Screening and/or unwilling to avoid smoking throughout the study.
- •Interstitial lung disease other than IPF.
- •Sustained improvement in the severity of IPF during the 12 months prior to screening.
- •Other types of respiratory diseases that, in the opinion of the Investigator, would impact the primary protocol endpoint or otherwise preclude participation in the study, including diseases of the airways, lung parenchyma, pleural space, mediastinum, diaphragm, or chest wall.
- •Certain medical conditions, that, in the opinion of the Investigator, would impact the primary protocol endpoint or otherwise preclude participation in the study (such as, myocardial infarction/stroke, severe chronic heart failure, pulmonary hypertension, or cancers).
- •Acute IPF exacerbation during Screening or Randomization including hospitalization due to acute IPF exacerbation within 4 weeks prior to or during screening.
- •Use of any investigational drugs or unapproved therapies, or participation in any clinical trial with an investigational new drug within 30 days prior to screening. Or use of approved IPF therapies (such as, pirfenidone or nintedanib) within 1 week prior to screening.
- •History of allergic or anaphylactic reaction to human, humanized, chimeric or murine monoclonal antibodies, or to any component of the excipient.
研究组 & 干预措施
Pamrevlumab
Treatment phase: Pamrevlumab 30 mg/kg administered by IV infusion, every 3 weeks, for a total of up to 17 infusions over 48 weeks.
Open-label extension phase: Pamrevlumab 30 mg/kg administered by intravenous infusion, every 3 weeks for up to 48 weeks
干预措施: Pamrevlumab (Drug)
Placebo
Pamrevlumab-matching placebo administered by IV infusion every 3 weeks for a total of up to 17 infusions over 48 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
DB Period: Change From Baseline in FVC at Week 48
时间窗: Baseline, Week 48
FVC is a standard pulmonary function test used to quantify respiratory muscle weakness. FVC was the volume of air that can forcibly be blown out after full inspiration in the upright position, measured in liters. Least square (LS) mean and standard error (SE) were analyzed using mixed model repeated measures (MMRM).
次要结局
- DB Period: Time to First Occurrence of Any Component of the Clinical Composite Endpoint, Whichever Occurred First(Up to Week 48)
- DB Period: Time to First Acute IPF Exacerbation(Up to Week 48)
- DB Period: Time to All-Cause Mortality(Up to Week 48)
- DB Period: Time to Disease Progression(Up to Week 48)
- DB Period: Time to First Respiratory Hospitalization(Up to Week 48)
- DB Period: Change From Baseline in Quantitative Lung Fibrosis (QLF) Volume at Week 48(Baseline, Week 48)