Denna sida har översatts automatiskt och översättningens korrekthet kan inte garanteras. Vänligen se engelsk version för en källtext.

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 augusti 2026 uppdaterad av: 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.

Studieöversikt

Status

Rekrytering

Betingelser

Intervention / Behandling

Studietyp

Interventionell

Inskrivning (Beräknad)

36

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studiekontakt

Studera Kontakt Backup

Studieorter

  • Frankrike
      • Besançon, Frankrike
        • Har inte rekryterat ännu
        • CHU de Besançon
        • Kontakt:
        • Huvudutredare:
          • Cindy BARNIG, Professor
      • Bordeaux, Frankrike
        • Har inte rekryterat ännu
        • Hopital Haut-Leveque - CHU Bordeaux
        • Kontakt:
        • Huvudutredare:
          • Elodie BLANCHARD, Doctor
      • Caen, Frankrike
        • Har inte rekryterat ännu
        • CHU Caen Normandie
        • Kontakt:
        • Huvudutredare:
          • Frederic RIVIERE, Doctor
      • Lille, Frankrike
        • Har inte rekryterat ännu
        • CHRU de Lille
        • Kontakt:
        • Huvudutredare:
          • Frederic WALLYN, Doctor
      • Paris, Frankrike
        • Har inte rekryterat ännu
        • Hôpital Saint-Louis APHP
        • Kontakt:
        • Huvudutredare:
          • Amira BENATTIA, Doctor
      • Suresnes, Frankrike, 92150
        • Rekrytering
        • Foch Hospital
        • Kontakt:
        • Huvudutredare:
          • Hélène SALVATOR, Professor

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

  • Vuxen
  • Äldre vuxen

Tar emot friska volontärer

Nej

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Arm 1
Läkemedel: 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.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Change in the annualized number of bronchial exacerbations
Tidsram: 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

Sekundära resultatmått

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

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

Hopital Foch

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

24 juni 2026

Primärt slutförande (Beräknad)

1 januari 2029

Avslutad studie (Beräknad)

1 januari 2029

Studieregistreringsdatum

Först inskickad

27 juli 2026

Först inskickad som uppfyllde QC-kriterierna

14 augusti 2026

Första postat (Faktisk)

18 augusti 2026

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

18 augusti 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

14 augusti 2026

Senast verifierad

1 augusti 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

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

Plan för individuella deltagardata (IPD)

Planerar du att dela individuella deltagardata (IPD)?

NEJ

Läkemedels- och apparatinformation, studiedokument

Studerar en amerikansk FDA-reglerad läkemedelsprodukt

Nej

Studerar en amerikansk FDA-reglerad produktprodukt

Nej

Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .

Prenumerera