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

NCT07771855 | Recruiting Phase 2

• 2 other identifiers: 2023_01862024-516796-33-00
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

HSCT; Bronchial Disease; Bronchiolitis Obliterans Syndrome (BOS)

Keywords

Efficacy anti-TSLP monoclonal antibody (tezepelumab) in chronic bronchial disease induced Bronchiolitis obliterans syndrome (BOS) in HSCT recipient.; BOS; HSCT; tezepzlumab

Outcome Measures

Primary Outcomes (1)

• Change in the annualized number of bronchial exacerbations

  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

Secondary Outcomes (26)

• Number of days alive and without bronchial exacerbation

  13 months

• Number of days alive and without hospitalization

  13 months

• Change in corticosteroid regimen

  13 months

• Change in Asthma Control Questionnaire 6 (ACQ-6) score

  13 months

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

  13 months

Study Arms (1)

Arm 1

EXPERIMENTAL

Drug: Tezepelumab

Interventions

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.

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hopital Foch: lead

Study Sites (6)

CHU de Besançon

Besançon, France

NOT YET RECRUITING

Hôpital Haut-Lévêque - CHU Bordeaux

Bordeaux, France

NOT YET RECRUITING

CHU Caen Normandie

Caen, France

NOT YET RECRUITING

CHRU de Lille

Lille, France

NOT YET RECRUITING

Hôpital Saint-Louis APHP

Paris, France

NOT YET RECRUITING

Foch Hospital

Suresnes, 92150, France

RECRUITING

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Bronchial Diseases

Interventions

tezepelumab

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Central Study Contacts

Yahya DEBZA

CONTACT

+33 1 46 25 36 42; y.debza@hopital-foch.com

DRCI Promotion

CONTACT

drci-promotion@hopital-fcoh.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: August 18, 2026
• Study Start: June 24, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2029
• Last Updated: August 18, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6)