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.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hospital Foch

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2026-05-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective of this study is to evaluate the efficacy of Tezepelumab in reducing the number of bronchial exacerbations after 12 months of treatment, taking into account the T2 immune respiratory profile.

Secondary objectives 4

1. To test the performance of tezepelumab on the improvement of respiratory symptoms and sparing in corticosteroids (inhaled or systemic route)
2. To test the performance of tezepelumab on the improvement of lung function (plethysmography: FEV1, FEV1/VC, RV/TLC and oscillometry: R5, R20, R20-R5, X5)
3. To describe the bronchial immunological profile of patients with chronic obstructive bronchial disease post-BOS with a focus on T2 immune profile, and its evolution under treatment with tezepelumab
4. Exploratory study: To assess the value of exhaled breath analyzes for the monitoring of patients on tezepelumab. The study of volatile organic compounds (VOCs) in exhaled air is an innovative area of research for respiratory diseases. We have set up a platform (Exhalomics©) at Foch Hospital dedicated to this type of analysis, including mass spectrometry and electronic noses, for the identification of VOC profiles in exhaled air. VOC analyzes are completely non-invasive and have already shown their interest as a tool for diagnosing or monitoring respiratory diseases (10). In a subgroup of patients (recruited at the Foch hospital center), we will seek to study the variation of VOCs induced by the targeting of TSLP pathways, and their correlation with the control of the bronchial disease and other biomarkers in blood and sputum.

Conditions and MedDRA coding

The medical condition studied in IMMUNO-BOS is Bronchiolitis obliterans syndrome (BOS) after allogeneic stem cell transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

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.
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 10

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is the 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. Bronchial exacerbations will be defined as acute bronchial symptoms lasting more than 48h and requiring hospitalization and/or anti infectious or corticosteroids.

Secondary endpoints 4

1. Endpoints evaluating the improvement of respiratory symptoms and corticosteroids sparing (secondary objective n°1): Clinical outcomes: • Number of days alive and not exacerbating • Number of days alive and not hospitalized • Reduction in corticosteroids regimen (inhaled and/or systemic route) Outcomes from validated questionnaires: • ACQ6 score (Asthma Control Questionnaire 6) • Breathlessness, Cough and Sputum Scale (BCSS) • St George Respiratory Questionnaire (SGRQ)
2. 2 Functionnal outcomes: • Pre-bronchodilator spirometry [forced expiratory volume in 1 second, forced vital capacity and the FEV1/FVC ratio. • Pre- bronchodilator plethysmography [total lung capacity, residual volume and the TLC/RV ratio] • Inspiratory and expiratory oscillometry parameters: resistance at 5 Hz, reactance at 5 Hz, Frequence of resonnance
3. Immunological outcomes: • Blood eosinophilia (absolute count, G/L) • Eosinophilia in induced sputum (relative count, %) • Blood total IgE count (kUI/L)
4. Exhalomic outcomes Unsupervised analysis of VOCs in exhaled air of patients blowing in a quadrupole-time-of-flight mass spectrometer (PTR-Qi-TOF MS; Ionicon, Innsbruck, Austria). Identification of VOCs (peaks corresponding to m/z) significantly changing over the year of treatment and correlation with clinical and biological readouts.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hospital Foch

Sponsor organisation

Hospital Foch

Address

40 Rue Worth

City

Suresnes

Postcode

92150

Country

France

Scientific contact point

Organisation

Hospital Foch

Contact name

Helene Salvator

Public contact point

Organisation

Hospital Foch

Contact name

Helene Salvator

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications