Efficacy of an Anti-TSLP Monoclonal Antibody in the Management of Chronic Bronchial Disease Induced by Bronchiolitis Obliterans Syndrome in Allogeneic Hematopoietic Stem Cells Transplantation Recipients (IMMUNO-BOS)
2026年8月14日 更新者：Hopital Foch
Allogeneic hematopoietic stem cell transplantation (HSCT) is burdened with a high morbidity and mortality rates. Graft versus host disease (GVHD) is the clinical manifestation of an immune conflict. The expression of GVHD in the bronchioles is responsible for bronchiolitis obliterans syndrome (BOS), defined by the appearance of an obstructive ventilatory disorder. BOS may affect up to 10% of allogeneic transplant recipients. Repeated aggression-repair phenomena of the bronchial epithelium lead to an irreversible fibrous remodeling. The management of BOS remains a therapeutic challenge. A number of patients worsen their ventilatory disorder despite the available treatments and progress to obstructive respiratory failure complicated by repeated bronchial exacerbations. When the patient is far from the allograft and in the absence of any sign of active extrathoracic GVHD, the mechanisms of aggravation of the ventilatory disorder are equivocal. It seems more likely that the bronchial disease evolves on its own due to a persistent local inflammation without any immunological conflict. In this case, it would be reasonable to model the management on that of severe bronchial diseases for which the logic of cortisone sparing is now permitted by the arrival of targeted biotherapies.
Since 2006, the therapeutic arsenal of bronchial inflammatory pathologies, mainly asthma, has been enriched with the class of targeted biotherapies. These therapies, targeting IgE (omalizumab), Th2 cytokines IL-5, IL-4, IL-13 (mepolizumab, benralizumab, dupilumab) and more recently the cytokine derived from the bronchial epithelium TSLP (tezepelumab), have shown effectiveness in reducing bronchial exacerbations, improving quality of life and reducing dependence on corticosteroids. TSLP is an alarmin that reflects bronchial epithelial involvement.
The objective of this study is to test the performance of an anti-TSLP biotherapy (tezepelumab) in the reduction of bronchial exacerbations in alloHSCT recipients suffering from obstructive bronchial disorders not supposed to be still related to an active GVHD.
研究概览
研究类型
介入性
注册 (估计的)
36
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。
学习联系方式
- 姓名：Yahya DEBZA
- 电话号码：+33 1 46 25 36 42
- 邮箱：y.debza@hopital-foch.com
研究联系人备份
- 姓名：DRCI Promotion
- 邮箱：drci-promotion@hopital-fcoh.com
学习地点
-
-
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Besançon、法国
- 尚未招聘
- CHU de Besançon
-
接触：
- Cindy BARNIG, Professor
- 邮箱：cbarnig@chu-besancon.fr
-
首席研究员：
- Cindy BARNIG, Professor
-
Bordeaux、法国
- 尚未招聘
- Hopital Haut-Leveque - CHU Bordeaux
-
接触：
- Elodie BLANCHARD, Doctor
- 邮箱：elodie.blanchard@chu-bordeaux.fr
-
首席研究员：
- Elodie BLANCHARD, Doctor
-
Caen、法国
- 尚未招聘
- CHU Caen Normandie
-
接触：
- Frederic RIVIERE, Doctor
- 邮箱：riviere-f@chu-caen.fr
-
首席研究员：
- Frederic RIVIERE, Doctor
-
Lille、法国
- 尚未招聘
- CHRU de Lille
-
接触：
- Frederic WALLYN, Doctor
- 邮箱：frederic.wallyn@chu-lille.fr
-
首席研究员：
- Frederic WALLYN, Doctor
-
Paris、法国
- 尚未招聘
- Hôpital Saint-Louis APHP
-
接触：
- Amira BENATTIA, Doctor
- 邮箱：amira.benattia@aphp.fr
-
首席研究员：
- Amira BENATTIA, Doctor
-
Suresnes、法国、92150
- 招聘中
- Foch Hospital
-
接触：
- Hélène SALVATOR, Professor
- 电话号码：+33 1 46 25 24 95
- 邮箱：h.salvator@hopital-foch.com
-
首席研究员：
- Hélène SALVATOR, Professor
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-
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
- 成人
- 年长者
接受健康志愿者
不
描述
Inclusion Criteria:
- Adult recipients, minimum age 18
- Recipient of an allogeneic bone marrow or haematopoietic stem cell transplant
- At more than 3 years after the date of the transplantation
- BOS defined by the occurrence of a new fixed obstructive ventilatory disorder after the allograft (accepted criteria: FEV1/FVC ≤70% and FEV1 < 75% pred value and decline of more than 10% over less than 2 years OR FEV1/FVC > 70% and FEV1 < 75% pred value and decline of FEV1 more than 10% over less than 2 years and Normal TLC > 80% OR decline of FEV1 more than 10% over less than 2 years and TLC > 120% and/or RV/TLC > 40%)
- Presenting an exacerbation profile: 2 or more moderate to severe bronchial exacerbations in the previous 12 months
- On optimal inhaled therapy comprising at least one long-acting bronchodilator and one inhaled corticosteroid for at least three months.
- Stable dose of systemic immunosuppressive regimen for the last 4 weeks
- Being covered by a national health insurance
- Signed consent form
Exclusion Criteria:
- Patients with an indication to increase their immunosuppressive treatment, in particular due to active GVH
- FEV1< 20% theorical value
- Being deprived of liberty or under guardianship
- Absence of signed consent
- Hypersensitivity (allergy) to tezelumab or to any of the excipients of TEZPIRE
- A helminth parasitic infection diagnosed within 6 months prior to Visit 1 that has not been treated with, or has failed to respond to, standard of care therapy
- Respiratory infection in the course of treatement (including acute bacterial and viral infection, long term treatment for fungal or non-tuberculosis mycobacteria)
- History of documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy
- Severe GVHD scleroderma-like manifestations of skin making subcutaneous injections of the investigational treatment impossible or overly difficult
- Pregnant, breastfeeding or lactating women
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：手臂 1
|
Participants will receive tezepelumab (TEZSPIRE®) 210 mg by subcutaneous injection once every 4 weeks for 12 months, starting with one injection on the day of enrollment.
The investigational product is supplied as a pre-filled syringe containing 210 mg of tezepelumab in 1.91 mL (110 mg/mL).
A total of 13 subcutaneous injections are planned during the study.
The first injection at enrollment and injections at Visits 4, 7, 10 and 13 will be administered at the investigation center.
Injections at Visits 2, 3, 5, 6, 8, 9, 11 and 12 will be administered at the participant's home by a nurse from the Libhéros network.
|
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 in the annualized number of bronchial exacerbations
大体时间：13 months
|
Within-patient change in the annualized number of bronchial exacerbations between the 12-month period prior to treatment initiation and the 12-month treatment period
|
13 months
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Number of days alive and without bronchial exacerbation
大体时间：13 months
|
Number of days during the study period during which the participant is alive and without bronchial exacerbation.
Unit of measure: days.
|
13 months
|
|
Number of days alive and without hospitalization
大体时间：13 months
|
Number of days during the study period during which the participant is alive and without hospitalization.
|
13 months
|
|
Change in corticosteroid regimen
大体时间：13 months
|
Change in corticosteroid regimen, including inhaled and/or systemic corticosteroid therapy.
|
13 months
|
|
Change in Asthma Control Questionnaire 6 (ACQ-6) score
大体时间：13 months
|
Change in the Asthma Control Questionnaire 6 (ACQ-6) score during the study period.
Unit of measure: score, ranging from 0 to 6.
|
13 months
|
|
Change in Breathlessness, Cough and Sputum Scale (BCSS) score
大体时间：13 months
|
Change in the Breathlessness, Cough and Sputum Scale (BCSS) total score during the study period.
Unit of measure: score, ranging from 0 to 4.
|
13 months
|
|
Change in St George's Respiratory Questionnaire (SGRQ) score
大体时间：13 months
|
Change in the St George's Respiratory Questionnaire (SGRQ) total score during the study period.
Unit of measure: score, ranging from 0 to 100.
|
13 months
|
|
Change in forced expiratory volume in 1 second (FEV1)
大体时间：13 months
|
Change in forced expiratory volume in 1 second (FEV1), measured by spirometry before and after bronchodilator administration.
Unit of measure: liters (L).
|
13 months
|
|
Change in forced expiratory volume in 1 second (FEV1) percent predicted
大体时间：13 months
|
Change in forced expiratory volume in 1 second (FEV1), expressed as a percentage of the predicted value and measured by spirometry before and after bronchodilator administration.
Unit of measure: percent (%).
|
13 months
|
|
Change in forced vital capacity (FVC)
大体时间：13 months
|
Change in forced vital capacity (FVC), measured by spirometry before and after bronchodilator administration.
Unit of measure: liters (L).
|
13 months
|
|
Change in forced vital capacity (FVC) percent predicted
大体时间：13 months
|
Change in forced vital capacity (FVC), expressed as a percentage of the predicted value and measured by spirometry before and after bronchodilator administration.
Unit of measure: percent (%).
|
13 months
|
|
Change in FEV1/FVC ratio
大体时间：13 months
|
Change in the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), measured by spirometry before and after bronchodilator administration.
Unit of measure: ratio (L/L).
|
13 months
|
|
Change in FEV1/FVC ratio expressed as a percentage
大体时间：13 months
|
Change in the ratio of forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC), measured by spirometry before and after bronchodilator administration.
Unit of measure: percent (%).
|
13 months
|
|
Change in total lung capacity (TLC)
大体时间：13 months
|
Change in total lung capacity (TLC), measured by plethysmography before bronchodilator administration.
Unit of measure: liters (L).
|
13 months
|
|
Change in total lung capacity (TLC) percent predicted
大体时间：13 months
|
Change in total lung capacity (TLC), expressed as a percentage of the predicted value and measured by plethysmography before bronchodilator administration.
Unit of measure: percent (%).
|
13 months
|
|
Change in residual volume (RV)
大体时间：13 months
|
Change in residual volume (RV), measured by plethysmography before bronchodilator administration.
Unit of measure: liters (L).
|
13 months
|
|
Change in residual volume (RV) percent predicted
大体时间：13 months
|
Change in residual volume (RV), expressed as a percentage of the predicted value and measured by plethysmography before bronchodilator administration.
Unit of measure: percent (%).
|
13 months
|
|
Change in TLC/RV ratio
大体时间：13 months
|
Change in the ratio of total lung capacity (TLC) to residual volume (RV), measured by plethysmography before bronchodilator administration.
Unit of measure: ratio (L/L).
|
13 months
|
|
Change in respiratory resistance at 5 Hz (R5)
大体时间：13 months
|
Change in respiratory resistance at 5 Hz (R5), measured by inspiratory and expiratory oscillometry.
Unit of measure: not specified in the protocol.
|
13 months
|
|
Change in respiratory resistance at 20 Hz (R20)
大体时间：13 months
|
Change in respiratory resistance at 20 Hz (R20), measured by inspiratory and expiratory oscillometry.
Unit of measure: not specified in the protocol.
|
13 months
|
|
Change in respiratory resistance difference between 20 Hz and 5 Hz (R20-R5)
大体时间：13 months
|
Change in the difference between respiratory resistance at 20 Hz and 5 Hz (R20-R5), measured by inspiratory and expiratory oscillometry.
Unit of measure: not specified in the protocol.
|
13 months
|
|
Change in respiratory reactance at 5 Hz (X5)
大体时间：13 months
|
Change in respiratory reactance at 5 Hz (X5), measured by inspiratory and expiratory oscillometry.
Unit of measure: not specified in the protocol.
|
13 months
|
|
Change in frequency of resonance (Fr)
大体时间：13 months
|
Change in frequency of resonance (Fr), measured by inspiratory and expiratory oscillometry.
Unit of measure: hertz (Hz).
|
13 months
|
|
Change in blood eosinophil count
大体时间：13 months
|
Change in blood eosinophil count during the study period.
Unit of measure: G/L.
|
13 months
|
|
Change in eosinophil count in induced sputum
大体时间：13 months
|
Change in eosinophil count in induced sputum during the study period.
Unit of measure: percent (%).
|
13 months
|
|
Change in blood total IgE level
大体时间：13 months
|
Change in blood total IgE level during the study period.
Unit of measure: kUI/L.
|
13 months
|
|
Annualized hospitalization rate per patient-year
大体时间：13 months
|
Number of hospitalization events occurring during the study period, standardized per patient-year.
Unit of measure: hospitalizations per patient-year.
|
13 months
|
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
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)
2026年6月24日
初级完成 (估计的)
2029年1月1日
研究完成 (估计的)
2029年1月1日
研究注册日期
首次提交
2026年7月27日
首先提交符合 QC 标准的
2026年8月14日
首次发布 (实际的)
2026年8月18日
研究记录更新
最后更新发布 (实际的)
2026年8月18日
上次提交的符合 QC 标准的更新
2026年8月14日
最后验证
2026年8月1日
更多信息
与本研究相关的术语
关键字
其他相关的 MeSH 术语
其他研究编号
- 2023_0186
- 2024-516796-33-00 (克蒂斯)
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不
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