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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.

調査の概要

状態

募集

条件

介入・治療

研究の種類

介入

入学 (推定)

36

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究連絡先のバックアップ

研究場所

  • フランス
      • Besançon、フランス
        • まだ募集していません
        • CHU de Besançon
        • コンタクト：
        • 主任研究者：
          • Cindy BARNIG, Professor
      • Bordeaux、フランス
        • まだ募集していません
        • Hopital Haut-Leveque - CHU Bordeaux
        • コンタクト：
        • 主任研究者：
          • Elodie BLANCHARD, Doctor
      • Caen、フランス
        • まだ募集していません
        • CHU Caen Normandie
        • コンタクト：
        • 主任研究者：
          • Frederic RIVIERE, Doctor
      • Lille、フランス
        • まだ募集していません
        • CHRU de Lille
        • コンタクト：
        • 主任研究者：
          • Frederic WALLYN, Doctor
      • Paris、フランス
        • まだ募集していません
        • Hôpital Saint-Louis APHP
        • コンタクト：
        • 主任研究者：
          • Amira BENATTIA, Doctor
      • Suresnes、フランス、92150
        • 募集
        • Foch Hospital
        • コンタクト：
        • 主任研究者：
          • Hélène SALVATOR, Professor

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

  • 大人
  • 高齢者

健康ボランティアの受け入れ

いいえ

説明

Inclusion Criteria:

  1. Adult recipients, minimum age 18
  2. Recipient of an allogeneic bone marrow or haematopoietic stem cell transplant
  3. At more than 3 years after the date of the transplantation
  4. 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%)
  5. Presenting an exacerbation profile: 2 or more moderate to severe bronchial exacerbations in the previous 12 months
  6. On optimal inhaled therapy comprising at least one long-acting bronchodilator and one inhaled corticosteroid for at least three months.
  7. Stable dose of systemic immunosuppressive regimen for the last 4 weeks
  8. Being covered by a national health insurance
  9. Signed consent form

Exclusion Criteria:

  1. Patients with an indication to increase their immunosuppressive treatment, in particular due to active GVH
  2. FEV1< 20% theorical value
  3. Being deprived of liberty or under guardianship
  4. Absence of signed consent
  5. Hypersensitivity (allergy) to tezelumab or to any of the excipients of TEZPIRE
  6. 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
  7. Respiratory infection in the course of treatement (including acute bacterial and viral infection, long term treatment for fungal or non-tuberculosis mycobacteria)
  8. History of documented immune complex disease (Type III hypersensitivity reactions) following any biologic therapy
  9. Severe GVHD scleroderma-like manifestations of skin making subcutaneous injections of the investigational treatment impossible or overly difficult
  10. Pregnant, breastfeeding or lactating women

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：なし
  • 介入モデル：単一グループの割り当て
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：アーム1
薬：Tezepelumab
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.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Change in the annualized number of bronchial exacerbations
時間枠：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

二次結果の測定

結果測定
メジャーの説明
時間枠
Number of days alive and without bronchial exacerbation
時間枠：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
時間枠：13 months
Number of days during the study period during which the participant is alive and without hospitalization.
13 months
Change in corticosteroid regimen
時間枠：13 months
Change in corticosteroid regimen, including inhaled and/or systemic corticosteroid therapy.
13 months
Change in Asthma Control Questionnaire 6 (ACQ-6) score
時間枠：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
時間枠：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
時間枠：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)
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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)
時間枠：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
時間枠：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)
時間枠：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
時間枠：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
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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)
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：13 months
Number of hospitalization events occurring during the study period, standardized per patient-year. Unit of measure: hospitalizations per patient-year.
13 months

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

Hopital Foch

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2026年6月24日

一次修了 (推定)

2029年1月1日

研究の完了 (推定)

2029年1月1日

試験登録日

最初に提出

2026年7月27日

QC基準を満たした最初の提出物

2026年8月14日

最初の投稿 (実際)

2026年8月18日

学習記録の更新

投稿された最後の更新 (実際)

2026年8月18日

QC基準を満たした最後の更新が送信されました

2026年8月14日

最終確認日

2026年8月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • 2023_0186
  • 2024-516796-33-00 (Ctis)

個々の参加者データ (IPD) の計画

個々の参加者データ (IPD) を共有する予定はありますか?

いいえ

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

いいえ

米国FDA規制機器製品の研究

いいえ

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