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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)

14 augustus 2026 bijgewerkt door: 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.

Studie Overzicht

Toestand

Werving

Conditie

Interventie / Behandeling

Studietype

Ingrijpend

Inschrijving (Geschat)

36

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Contact Back-up

Studie Locaties

  • Frankrijk
      • Besançon, Frankrijk
        • Nog niet aan het werven
        • CHU de Besançon
        • Contact:
        • Hoofdonderzoeker:
          • Cindy BARNIG, Professor
      • Bordeaux, Frankrijk
        • Nog niet aan het werven
        • Hopital Haut-Leveque - CHU Bordeaux
        • Contact:
        • Hoofdonderzoeker:
          • Elodie BLANCHARD, Doctor
      • Caen, Frankrijk
        • Nog niet aan het werven
        • CHU Caen Normandie
        • Contact:
        • Hoofdonderzoeker:
          • Frederic RIVIERE, Doctor
      • Lille, Frankrijk
        • Nog niet aan het werven
        • CHRU de Lille
        • Contact:
        • Hoofdonderzoeker:
          • Frederic WALLYN, Doctor
      • Paris, Frankrijk
        • Nog niet aan het werven
        • Hôpital Saint-Louis APHP
        • Contact:
        • Hoofdonderzoeker:
          • Amira BENATTIA, Doctor
      • Suresnes, Frankrijk, 92150
        • Werving
        • Foch Hospital
        • Contact:
        • Hoofdonderzoeker:
          • Hélène SALVATOR, Professor

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Beschrijving

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

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: NVT
  • Interventioneel model: Opdracht voor een enkele groep
  • Masker: Geen (open label)

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Experimenteel: Arm 1
Geneesmiddel: 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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change in the annualized number of bronchial exacerbations
Tijdsspanne: 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

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Number of days alive and without bronchial exacerbation
Tijdsspanne: 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
Tijdsspanne: 13 months
Number of days during the study period during which the participant is alive and without hospitalization.
13 months
Change in corticosteroid regimen
Tijdsspanne: 13 months
Change in corticosteroid regimen, including inhaled and/or systemic corticosteroid therapy.
13 months
Change in Asthma Control Questionnaire 6 (ACQ-6) score
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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)
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 13 months
Number of hospitalization events occurring during the study period, standardized per patient-year. Unit of measure: hospitalizations per patient-year.
13 months

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Hopital Foch

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

24 juni 2026

Primaire voltooiing (Geschat)

1 januari 2029

Studie voltooiing (Geschat)

1 januari 2029

Studieregistratiedata

Eerst ingediend

27 juli 2026

Eerst ingediend dat voldeed aan de QC-criteria

14 augustus 2026

Eerst geplaatst (Werkelijk)

18 augustus 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

18 augustus 2026

Laatste update ingediend die voldeed aan QC-criteria

14 augustus 2026

Laatst geverifieerd

1 augustus 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

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

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

NEE

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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