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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Hopital Foch
- 入组人数
- 36
- 试验地点
- 6
- 主要终点
- Change in the annualized number of bronchial exacerbations
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Change in the annualized number of bronchial exacerbations
时间窗: 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
次要结局
- Change in blood total IgE level(13 months)
- 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)
- Change in St George's Respiratory Questionnaire (SGRQ) score(13 months)
- Change in forced expiratory volume in 1 second (FEV1)(13 months)
- Change in forced expiratory volume in 1 second (FEV1) percent predicted(13 months)
- Change in forced vital capacity (FVC)(13 months)
- Change in forced vital capacity (FVC) percent predicted(13 months)
- Change in FEV1/FVC ratio(13 months)
- Change in FEV1/FVC ratio expressed as a percentage(13 months)
- Change in total lung capacity (TLC)(13 months)
- Change in total lung capacity (TLC) percent predicted(13 months)
- Change in residual volume (RV)(13 months)
- Change in residual volume (RV) percent predicted(13 months)
- Change in TLC/RV ratio(13 months)
- Change in respiratory resistance at 5 Hz (R5)(13 months)
- Change in respiratory resistance at 20 Hz (R20)(13 months)
- Change in respiratory resistance difference between 20 Hz and 5 Hz (R20-R5)(13 months)
- Change in respiratory reactance at 5 Hz (X5)(13 months)
- Change in frequency of resonance (Fr)(13 months)
- Change in blood eosinophil count(13 months)
- Change in eosinophil count in induced sputum(13 months)
- Annualized hospitalization rate per patient-year(13 months)