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Itepekimab对COPD患者气道炎症影响的机制研究 (AERIFY-3)

2026年8月26日 更新者：Sanofi

评估 Itepekimab（抗 IL-33 单克隆抗体）对慢性阻塞性肺疾病 (COPD) 患者气道炎症作用机制的 2a 期、开放标签、两部分研究

本研究是一项为期 12 周、分为两部分的探索性 2a 期研究，旨在评估 Itepekimab（抗 IL-33-mAb）的作用机制及其对 40 岁患有 COPD 的既往吸烟者和目前吸烟者气道炎症的影响到 70 岁。

本研究由接受标准治疗 (SoC) 单药（长效 β2 激动剂 [LABA]）或长效毒蕈碱拮抗剂 [LAMA]、双药（吸入皮质类固醇 [ICS] + LABA）的参与者组成、LABA + LAMA 或 ICS + LAMA）或三联（ICS + LABA + LAMA）控制剂治疗筛选前至少 3 个月的 COPD（访视 1），在筛选前至少 1 个月采用稳定剂量和方案进行控制性治疗（访问 1）和筛选期间。 在整个研究期间，参与者将继续使用既定的 COPD 控制药物，但用于 COPD 急性加重 (AECOPD) 的全身性皮质类固醇和/或抗生素除外。

每个部分（A 部分和 B 部分）的总学习时间约为 36 周：

  • 4周的筛选期
  • 12周治疗期
  • 20周的随访期

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

49

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 丹麦
      • Aalborg、丹麦、9000
        • Investigational Site Number : 2080003
      • Copenhagen、丹麦、2400
        • Investigational Site Number : 2080001
      • Hvidovre、丹麦、2650
        • Investigational Site Number : 2080002
  • 巴西
      • São Paulo、巴西、01323-900
        • Hospital Beneficência Portuguesa de São Paulo- Site Number : 0760005
    • Rio Grande do Sul
      • Porto Alegre、Rio Grande do Sul、巴西、90610-000
        • Hospital São Lucas da PUCRS - Porto Alegre - Avenida Ipiranga- Site Number : 0760003
    • São Paulo
      • Campinas、São Paulo、巴西、13059-900
        • Hospital e Maternidade Celso Pierro - PUC-Campinas- Site Number : 0760004
      • Votuporanga、São Paulo、巴西、15501-405
        • Integral Pesquisa e Ensino- Site Number : 0760006
  • 德国
      • Freiburg im Breisgau、德国、79106
        • Investigational Site Number : 2760005
      • Großhansdorf、德国、22926
        • Investigational Site Number : 2760001
      • Peine、德国、31224
        • Investigational Site Number : 2760004
  • 比利时
      • Edegem、比利时、2650
        • Investigational Site Number : 0560001
  • 美国
    • California
      • Torrance、California、美国、90509
        • UCLA Medical Center - Harbor- Site Number : 8400006
    • Colorado
      • Denver、Colorado、美国、80206
        • National Jewish Health Medical Center- Site Number : 8400012
    • Florida
      • Miami、Florida、美国、33125
        • University of Miami UHealth Tower- Site Number : 8400015
    • Missouri
      • Kansas City、Missouri、美国、66160
        • University of Kansas Medical Center- Site Number : 8400004
    • Oklahoma
      • Oklahoma City、Oklahoma、美国、73120
        • Allergy, Asthma and Clinical Research- Site Number : 8400010
    • Pennsylvania
      • DuBois、Pennsylvania、美国、15801
        • Clinical Research Associates of Central PA - Dubois- Site Number : 8400011
    • Texas
      • Dallas、Texas、美国、75390
        • University of Texas - Southwestern Medical Center- Site Number : 8400014
  • 英国
      • Liverpool、英国、L9 7AL
        • Investigational Site Number : 8260002
    • Cheshire West And Chester
      • Wythenshawe、Cheshire West And Chester、英国、M23 9QZ
        • Investigational Site Number : 8260003
    • London, City of
      • London、London, City of、英国、W2 1NY
        • Investigational Site Number : 8260004
    • Nottinghamshire
      • Nottingham、Nottinghamshire、英国、NG5 1PB
        • Investigational Site Number : 8260001
  • 荷兰
      • Groningen、荷兰、9713 GZ
        • Investigational Site Number : 5280001

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

40年 至 70年 (成人、年长者)

接受健康志愿者

不

描述

纳入标准：

  • 参与者必须年满 40 至 70 岁（含）
  • COPD 医生诊断至少 1 年（根据慢性阻塞性肺病全球倡议 [GOLD] 定义）。

  • 吸烟史≥10包年

    • 对于以前的吸烟者：报告他们目前不吸烟并且戒烟的参与者必须在筛选（访问 1）之前 ≥ 6 个月发生并有永久戒烟的意图。
    • 对于当前吸烟者（不符合 A 部分的资格）：在筛选（访问 1）和基线时报告他们目前正在吸烟的参与者（参与者在过去 7 天内平均每天至少吸 5 支香烟），并且当前未参与或计划在筛选（访视 1）或筛选期间开始戒烟干预。
  • 参与者报告的慢性支气管炎体征和症状史（筛选前一年慢性咳嗽至少 3 个月的慢性咳嗽的其他原因[例如，未充分治疗的胃食管反流或慢性鼻窦炎；或临床诊断支气管扩张症]已被排除）。

  • 记录的或自我报告的恶化史在筛选前 5 年内有≥1 次中度或重度恶化（访问 1），至少有 1 次恶化用全身性皮质类固醇治疗：

    • 中度恶化定义为呼吸系统症状急性恶化，需要全身性皮质类固醇（肌肉注射 [IM]、静脉注射 [IV] 或口服）和/或抗生素。
    • 严重恶化定义为 AECOPD，需要住院或在急诊室/紧急护理机构观察 >24 小时。
  • 参与者在筛选前接受 SoC 控制疗法治疗 ≥ 3 个月（访问 1），并且在筛选访问前和筛选期间接受稳定剂量和控制疗法治疗至少 1 个月，包括：LAMA + LABA 三联疗法+ ICS 或 ICS + LABA 或 LABA + LAMA 或 ICS + LAMA 双重疗法，或 LABA 或 LAMA 单一疗法。
  • 已根据当地针对严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 的建议接受适当疫苗接种的参与者，至少在筛选前 1 周接种疫苗（访问 1）。
  • 体重指数（BMI）≥18 kg/m2

  • 如果女性参与者没有怀孕，没有母乳喂养，并且至少满足以下条件之一，则有资格参加：

    • 不是有生育能力的女性 (WOCBP) 或
    • WOCBP 同意在干预期间和最后一次研究干预后至少 20 周内遵守避孕指南。

排除标准：

  • 根据全球哮喘防治倡议 (GINA) 指南，当前诊断或先前确诊的哮喘诊断，除非哮喘在 18 岁之前解决并且没有复发。
  • 对于前吸烟者（A 部分和 B 部分）：在筛选（访视 1）前 6 个月内或筛选期间主动吸烟或吸食任何产品（例如，尼古丁、四氢大麻酚 [THC]）。 对于当前吸烟者（B 部分）：在筛选（访视 1）前 6 个月内或筛选期间吸食任何产品（例如，尼古丁、THC）。
  • 预计在筛选或治疗期间在室内环境中经常接触环境（即“二手”）烟草烟雾的参与者（仅限前吸烟者）。
  • 筛选前 6 个月内或筛选时（访视 1）出现可能影响参与者参与研究的具有临床意义的新异常心电图 (ECG)。
  • 除 COPD 以外的具有临床意义的当前肺部疾病，例如结节病、间质性肺病、支气管扩张症（临床诊断）、α1 抗胰蛋白酶缺乏症的诊断或其他已诊断的肺部疾病。
  • 肺心病的诊断、右心衰竭或中度至重度肺动脉高压的证据。
  • 需要超过 2 升/分钟的长期静息氧气治疗的参与者。 在运动期间使用高达 4 升/分钟的补充氧气的参与者可以报名参加。 允许在睡眠期间吸氧。
  • 需要双水平气道正压通气 (BiPAP) 的高碳酸血症。
  • 筛选前 8 周内（访视 1）或筛选期间出现中度或重度 COPD 恶化（AECOPD）。
  • 全肺切除术、肺叶切除术、肺段切除术或治疗性支气管镜手术（包括支气管镜减容术）的既往病史。 注意：手术肺活检或楔形切除术的既往史不是排除标准。
  • 计划在研究期间进行的任何手术或主要程序（包括需要清醒镇静的程序）。 允许进行较小的皮肤手术。
  • 不稳定的缺血性心脏病，包括筛选前 1 年内的急性心肌梗死（访问 1），或筛选前 6 个月内的不稳定型心绞痛（访问 1）或筛选期间。
  • 心律失常，包括阵发性（如间歇性）房颤。 可考虑纳入孤立性室性早搏 (PVC) 或房性早搏 (PAC) 的参与者。
  • 心肌病，如 III-IV 期（纽约心脏协会）心力衰竭所定义，或其他可能影响参与者参与研究的相关心血管疾病。
  • 任何需要预防心内膜炎的潜在疾病。
  • 未控制的高血压（即收缩压 [BP] >180 毫米汞柱或舒张压 >110 毫米汞柱，使用或不使用抗高血压治疗）。
  • 患有活动性结核病 (TB)、潜伏性结核病、结核病未完全治疗病史、疑似肺外结核感染 (TBI) 或感染结核病风险高（例如与活动性或潜伏性结核病患者密切接触）或接受过治疗的参与者卡介苗 (BCG) - 筛选前 12 周内接种疫苗（访问 1）。
  • 人类免疫缺陷病毒 (HIV) 感染史或筛选时 HIV 1/2 血清学阳性（访问 1）。
  • 怀疑或确诊 2019 冠状病毒病 (COVID-19) 感染或在筛选（访问 1）或筛选期间接触已知的 COVID19 接触者；筛选前 6 周内已知的 COVID19 感染史（访问 1）；筛选前 12 个月内因 COVID-19 而需要机械通气或体外膜肺氧合 (ECMO) 的病史（访问 1）；在筛选（访问 1）之前感染了 COVID-19 且尚未充分康复以参与临床试验程序的参与者。
  • 筛选前 6 周内（访问 1）或筛选期间需要使用抗菌、抗病毒、抗真菌、抗寄生虫或抗原生动物药物进行全身治疗的急性或慢性感染的证据，筛选前 6 周内（访问 1）或筛选期间的显着病毒感染可能未接受抗病毒治疗的筛查期（例如，仅接受对症治疗的流感）。
  • 患有活动性自身免疫性疾病或因自身免疫性疾病（例如，风湿性关节炎、炎症性肠病、原发性胆汁性肝硬化、系统性红斑狼疮、多发性硬化症）接受免疫抑制治疗的参与者。
  • 筛选前 5 年内（访问 1）或筛选期间的恶性肿瘤病史，除了完全治疗的宫颈原位癌、完全治疗和消退的非转移性鳞状或基底细胞皮肤癌。
  • 筛选前 3 个月内有症状的带状疱疹。
  • 以前使用 Itepekimab。

上述信息并非旨在包含与患者可能参与临床试验相关的所有考虑因素。

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：不适用
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：伊替匹单抗

该组包括来自 2 个人群的参与者：A 部分——前吸烟者和 B 部分——当前吸烟者。

每 2 周 (Q2W) 皮下 (SC) 给予 Itepekimab 一次，持续 12 周
药品：伊替匹单抗 SAR440340
剂型：预充式注射器注射液；给药途径： 皮下注射
其他名称：
  • REGN3500

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Change From Baseline in Itepekimab Pharmacodynamic Normalized Enrichment Score Derived From Former Smokers in Endobronchial Biopsies in Current Smokers With Chronic Obstructive Pulmonary Disease at Week 12
大体时间：Baseline (Week 0) and Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). The gene signatures are derived from the genes differentially expressed in endobronchial biopsies, bronchial brushings, and nasal brushings of former smokers. The NES in current smokers, at baseline and at Week 12, are calculated based on the gene signatures of former smokers. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Baseline (Week 0) and Week 12
Change From Baseline in Itepekimab Pharmacodynamic Normalized Enrichment Score Derived From Former Smokers in Bronchial Brushings in Current Smokers With Chronic Obstructive Pulmonary Disease at Week 12
大体时间：Baseline (Week 0) and Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). The gene signatures are derived from the genes differentially expressed in endobronchial biopsies, bronchial brushings, and nasal brushings of former smokers. The NES in current smokers, at baseline and at Week 12, are calculated based on the gene signatures of former smokers. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Baseline (Week 0) and Week 12
Change From Baseline in Itepekimab Pharmacodynamic Normalized Enrichment Score Derived From Former Smokers in Nasal Brushings in Current Smokers With Chronic Obstructive Pulmonary Disease at Week 12
大体时间：Baseline (Week 0) and Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). The gene signatures are derived from the genes differentially expressed in endobronchial biopsies, bronchial brushings, and nasal brushings of former smokers. The NES in current smokers, at baseline and at Week 12, are calculated based on the gene signatures of former smokers. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Baseline (Week 0) and Week 12

次要结果测量

结果测量
措施说明
大体时间
Change From Baseline in Interleukin-33 (IL-33) Treated Eosinophil-associated Normalized Enrichment Score in Endobronchial Biopsies at Week 12
大体时间：Baseline (Week 0) and Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). IL-33 treated eosinophil-associated gene signature is used to evaluate NES of endobronchial biopsies of former and current smokers, at baseline and Week 12. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Baseline (Week 0) and Week 12
Change From Baseline in Interleukin-33 Treated Mast Cell-associated Normalized Enrichment Score in Endobronchial Biopsies at Week 12
大体时间：Baseline (Week 0) and Week 12
The NES provides an indication of the difference in gene expression levels for a particular individual before and after treatment for a defined set of genes (or signature). IL-33 treated mast cell-associated gene signature is used to evaluate NES of endobronchial biopsies of former and current smokers, at baseline and Week 12. Change in NES from baseline indicates that the gene signature is differentially regulated in response to itepekimab, with up- and down-regulated genes changing in their expected directions. No predetermined directionality has been established for this score; therefore, a higher or lower NES does not indicate a better or worse outcome. Baseline was defined as the last available value before first dose of study treatment.
Baseline (Week 0) and Week 12
Change From Baseline to Week 12 in Blood Eosinophil Count
大体时间：Baseline (Week 0) and Week 12
Blood samples were collected at specified timepoints to assess change in blood eosinophil count. Baseline was defined as the last available value before first dose of study treatment.
Baseline (Week 0) and Week 12
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Adverse Event of Special Interests (TEAESIs), Treatment-emergent Serious Adverse Events (TESAEs), and TEAEs Leading to Permanent Treatment Discontinuation
大体时间：From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
An AE was defined as any untoward medical occurrence in participant or clinical study participant, temporally associated with use of study treatment, whether or not considered related to study treatment. An AE of special interest (AESI) was an AE (serious or nonserious) of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and immediate notification by Investigator to Sponsor was required. SAEs were defined as any AE that, at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect or was medically important event. TEAEs were defined as AEs that developed, worsened or became serious during TE period (from first study treatment administration up to end of study).
From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities (PCSA) in Hematology During the Treatment-emergent Period
大体时间：From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Blood samples were collected to determine the PCSA in hematology during the TE period (from the first treatment administration up to the end of study). Here, Hb = hemoglobin; g/L = grams per liter; M = male; F = female; v/v= volume by volume; LC = leukocyte count; NB = non-black; B = black; ULN = upper limit of normal and EO = eosinophils. Only parameters in which any participant had abnormality are reported.
From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Clinical Chemistry During the Treatment-emergent Period
大体时间：From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Blood samples were collected to determine the PCSA in chemistry during the TE period (first treatment administration up to the end of study). Here, mmol/L = millimoles/liter; LLN = lower limit of normal; mg/L = milligrams/liter and mcmol/L = micromoles/liter. Only parameters in which any participant had abnormality are reported.
From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Urinalysis During the Treatment-emergent Period
大体时间：From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Urine samples were collected to determine the PCSA in urine during the TE period (from the first treatment administration up to the end of study).
From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Vital Signs During the Treatment-emergent Period
大体时间：From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Participants were examined to determine the PCSA in vital signs during the TE period (from the first treatment administration up to the end of study). Here, SSBP = sitting systolic blood pressure; mmHg = millimeters of mercury; DFB = decrease from baseline and IFB = increase from baseline. Only parameters in which any participant had abnormality are reported.
From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) During the Treatment-emergent Period
大体时间：From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Single 12-lead ECGs were obtained to determine PCSA during the TE period (from the first treatment administration up to the end of study). Here, QTcB= QT interval corrected by Bazett's formula and QTcF= QT interval corrected by Fridericia formula. Only parameters in which any participant had abnormality are reported.
From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Number of Participants With Treatment-emergent Antidrug Antibodies (ADA) to Itepekimab
大体时间：From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Blood samples were collected to evaluate antibodies to itepekimab in serum. Treatment-emergent ADA response was defined as a positive response in the ADA assay post first dose when baseline results were negative or missing.
From first dose of study treatment administration (Week 0) up to end of study, 32 weeks
Serum Concentrations of Functional Itepekimab
大体时间：Pre-dose at Weeks 0, 4, 12 and 32
Blood samples were collected at specified timepoints to obtain serum concentrations of itepekimab.
Pre-dose at Weeks 0, 4, 12 and 32

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Sanofi

合作者

Regeneron Pharmaceuticals

调查人员

  • 研究主任：Clinical Sciences & Operations、Sanofi

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2022年5月19日

初级完成 (实际的)

2025年3月5日

研究完成 (实际的)

2025年7月25日

研究注册日期

首次提交

2022年4月6日

首先提交符合 QC 标准的

2022年4月6日

首次发布 (实际的)

2022年4月13日

研究记录更新

最后更新发布 (实际的)

2026年8月31日

上次提交的符合 QC 标准的更新

2026年8月26日

最后验证

2026年8月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • PDY16967
  • 2021-001654-65 (EudraCT编号)
  • U1111-1255-5322 (注册表标识符：ICTRP)
  • 2024-512007-39-00 (克蒂斯)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

合格的研究人员可以请求访问患者水平的数据和相关研究文件，包括临床研究报告、带有任何修订的研究方案、空白病例报告表、统计分析计划和数据集规范。 患者层面的数据将被匿名化，研究文件将被编辑以保护试验参与者的隐私。 有关赛诺菲数据共享标准、合格研究和请求访问流程的更多详细信息，请访问：https://vivli.org

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

在美国制造并从美国出口的产品

是的

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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