Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07771855

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

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Bronchiolitis Obliterans Syndrome (BOS) Bronchial Disease Bronchial Diseases Bronchiolitis Bronchiolitis Obliterans Bronchiolitis Obliterans Syndrome Bronchitis Graft vs Host Disease HSCT Immune System Diseases Lung Diseases Lung Diseases, Obstructive Organizing Pneumonia Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

CHU de Besançon, Besançon, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Tezepelumab

Drug

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.

Primary outcomes

  1. Change in the annualized number of bronchial exacerbations

    Time frame: 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

Secondary outcomes

  1. Number of days alive and without bronchial exacerbation

    Time frame: 13 months

    Number of days during the study period during which the participant is alive and without bronchial exacerbation. Unit of measure: days.

  2. Number of days alive and without hospitalization

    Time frame: 13 months

    Number of days during the study period during which the participant is alive and without hospitalization.

  3. Change in corticosteroid regimen

    Time frame: 13 months

    Change in corticosteroid regimen, including inhaled and/or systemic corticosteroid therapy.

  4. Change in Asthma Control Questionnaire 6 (ACQ-6) score

    Time frame: 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.

  5. Change in Breathlessness, Cough and Sputum Scale (BCSS) score

    Time frame: 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.

  6. Change in St George's Respiratory Questionnaire (SGRQ) score

    Time frame: 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.

  7. Change in forced expiratory volume in 1 second (FEV1)

    Time frame: 13 months

    Change in forced expiratory volume in 1 second (FEV1), measured by spirometry before and after bronchodilator administration. Unit of measure: liters (L).

  8. Change in forced expiratory volume in 1 second (FEV1) percent predicted

    Time frame: 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 (%).

  9. Change in forced vital capacity (FVC)

    Time frame: 13 months

    Change in forced vital capacity (FVC), measured by spirometry before and after bronchodilator administration. Unit of measure: liters (L).

  10. Change in forced vital capacity (FVC) percent predicted

    Time frame: 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 (%).

  11. Change in FEV1/FVC ratio

    Time frame: 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).

  12. Change in FEV1/FVC ratio expressed as a percentage

    Time frame: 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. Change in total lung capacity (TLC)

    Time frame: 13 months

    Change in total lung capacity (TLC), measured by plethysmography before bronchodilator administration. Unit of measure: liters (L).

  14. Change in total lung capacity (TLC) percent predicted

    Time frame: 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 (%).

  15. Change in residual volume (RV)

    Time frame: 13 months

    Change in residual volume (RV), measured by plethysmography before bronchodilator administration. Unit of measure: liters (L).

  16. Change in residual volume (RV) percent predicted

    Time frame: 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 (%).

  17. Change in TLC/RV ratio

    Time frame: 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).

  18. Change in respiratory resistance at 5 Hz (R5)

    Time frame: 13 months

    Change in respiratory resistance at 5 Hz (R5), measured by inspiratory and expiratory oscillometry. Unit of measure: not specified in the protocol.

  19. Change in respiratory resistance at 20 Hz (R20)

    Time frame: 13 months

    Change in respiratory resistance at 20 Hz (R20), measured by inspiratory and expiratory oscillometry. Unit of measure: not specified in the protocol.

  20. Change in respiratory resistance difference between 20 Hz and 5 Hz (R20-R5)

    Time frame: 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.

  21. Change in respiratory reactance at 5 Hz (X5)

    Time frame: 13 months

    Change in respiratory reactance at 5 Hz (X5), measured by inspiratory and expiratory oscillometry. Unit of measure: not specified in the protocol.

  22. Change in frequency of resonance (Fr)

    Time frame: 13 months

    Change in frequency of resonance (Fr), measured by inspiratory and expiratory oscillometry. Unit of measure: hertz (Hz).

  23. Change in blood eosinophil count

    Time frame: 13 months

    Change in blood eosinophil count during the study period. Unit of measure: G/L.

  24. Change in eosinophil count in induced sputum

    Time frame: 13 months

    Change in eosinophil count in induced sputum during the study period. Unit of measure: percent (%).

  25. Change in blood total IgE level

    Time frame: 13 months

    Change in blood total IgE level during the study period. Unit of measure: kUI/L.

  26. Annualized hospitalization rate per patient-year

    Time frame: 13 months

    Number of hospitalization events occurring during the study period, standardized per patient-year. Unit of measure: hospitalizations per patient-year.

Study contacts

Contact information is provided by the study sponsor or research team.

DRCI Promotion

CONTACT

[email protected]

Yahya DEBZA

CONTACT

[email protected]

+33 1 46 25 36 42

Sponsors and collaborators

Lead sponsor

Hopital Foch

Other

Registry information

Acronym: IMMUNO-BOS

Important dates

Study start
2026
Primary completion
2029
Study completion
2029
First posted
Aug 18, 2026
Registry last updated
Aug 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.