Novel Insight in pathologiCal and clinicAl Attributes in Response to mepoLizumab Treatment in Patients With Chronic rhInosinusitis With Nasal pOlyPs With or Without bronchIal Asthma on a Long-term Basis (CALIOPI STUDY)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 57
- 试验地点
- 2
- 主要终点
- Change in Basement Membrane Thickness
研究概览
简要总结
Mepolizumab is a biologic agent already approved for severe asthma. Recently, there is increasing evidence concerning the benefit of anti-IL5 treatments upon patients with nasal polyposis with or without severe asthma.
The novelty of this project is that no biologic agent has yet been fully investigated to identify any biomarkers of response for patients with nasal polyps with or without asthma including sinonasal tissue remodeling a key element in the resultant histopathological changes of the inflammation. The investigation of airway remodeling of various locations (nose and bronchus) under mepolizumab treatment will be our primary objective on the long-term basis of 156 weeks of treatment.
Endobronchial and nasal biopsies will be performed as routine care for tissue evauation and disease investigation for every patient.
Besides, the united airways will provide better guidance for medical treatment of chronic rhinosinusitis (CRS) patients with nasal polyps (CRSwNP) and asthma.
The initial idea is based on investigating the characteristics that could predict the effectiveness of mepolizumab on patients with nasal polyposis with or without asthma. Patients will receive 39 doses of mepolizumab for 156 weeks. An additional aim of this study is to identify characteristics of non-responders and responders to mepolizumab. Responders will be identified based on airway remodeling status, biomarkers in tissue and secretion samples and on the reduction of the need of surgery through Lund-Kennedy endoscopic score, Lund-Mackay score and patient's clinical status in the 6th, 12th and 36th month after the initiation of treatment.
Regarding the unified airway system, nose and pharyngeal microbiome will be evaluated before and after 52 weeks of mepolizumab treatment in patients with nasal polyps whereas in patients with nasal polyps and asthma bronchus microbiome will also be evaluated. Lung samples will help gain information about the inflammatory profile and local microbiome of CRSwNP patients with asthma through molecular and cellular assays. The human Pharyngeal Microbiome might play a protective role in Respiratory Tract Infections and it has been reported that the microbiome provides critical signals to promote maturation of immune cells and differentiation of the tissue. Thus, we will make an effort to correlate microbiome of various locations with clinical and laboratory characteristics of responders and non-responders to mepolizumab treatment.
详细描述
Hypothesis Identification of pathological and clinical characteristics of responders and non-responders to mepolizumab treatment in patients with chronic rhinosinusitis with nasal polyps with or without bronchial asthma regarding the airway remodeling, inflammatory cells and other biomarkers on a long-term basis.
Objectives/Endpoints
The primary objectives of this study are:
- Evaluation of the airway remodeling in various anatomic locations of the airways (nose, bronchus) at baseline-before treatment initiation and after 156 weeks of mepolizumab treatment.
- Identification of any characteristics in microbiome of various locations (nose, pharyngeal, bronchus) in responders and non-responders to mepolizumab treatment.
The key secondary objectives of this study are:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
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 patients > 18 years with bilateral Nasal Polyps
- •Symptoms VAS scores (for nasal obstruction, hyposmia, post-nasal drip, sneezing, rhinorrhea; 0-10 for each symptom) > 24 in spite of treatment with standard of care treatment.
- •Patients with bilateral sinonasal polyps with a need for surgery as described by: Lund-Mackay score > 4, Lund Kennedy score > 6, a minimum total Nasal polyp score of 5 out of a maximum score of 8 at screening, ongoing symptoms for at least 12 weeks prior to screening,
- •Concerning patients with asthmatics with nasal polyps: subjects must have a medical history of asthma as confirmed by asthma related symptoms and by bronchodilator response (BDR) (GINA 2022) or positive methacholine challenge according to ERS guidelines.
排除标准
- •Pregnant or nursing women, or women of child-bearing potential.
- •Biologic therapy (eg: Omalizumab, Mepolizumab, Reslizumab, Dupilumab) or previous treatment with Mepolizumab
- •Allergen immunotherapy in the past 6 months
- •Systemic corticosteroid treatment for other chronic conditions (i.e.: autoimmune disorders, tumors, etc)
- •Prior/concomitant therapy: use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, or any experimental anti-inflammatory therapy) within 3 months prior to Visit 1 and during the study period.
- •Evidence of active systemic immunodepression (i.e..: primary or secondary immunodeficiency)
- •History of malignancy of any organ system or any other serious co-morbidities defined by the treating physician.
- •Primary diagnosis of lung disease other than asthma (chronic obstructive lung disease (COPD), asthma-COPD overlap (ACO), interstitial lung disease, sarcoidosis, bronchiectasis, cystic fibrosis, primary ciliary dyskinesia, active tuberculosis, allergic bronchopulmonary aspergillosis (ABPA), current lung cancer or other blood, lymphatic or solid organ malignancy, autoimmune diseases of the skin, muscle-skeletal or gastrointestinal system needing systemic corticosteroids, immunosuppressants or biologic treatment as well as individuals with granulomatosis with polyangiitis (Wegener's granulomatosis) and eosinophilic granulomatosis polyangiitis (Churg-Strauss syndrome).
- •Nasal polyps' or Asthma exacerbation, within 12 weeks prior to screening that required oral corticosteroids over 3 days or hospitalization or emergency room visit.
研究组 & 干预措施
chronic rhinosinusitis with nasal polyps with bronchial asthma
Patients with chronic rhinosinusitis with nasal polyps with bronchial asthma will be administered Mepolizumab (100 MG), subcutaneusly every 30 days
干预措施: Mepolizumab 100 MG [Nucala] (Drug)
chronic rhinosinusitis with nasal polyps without bronchial asthma
Patients with chronic rhinosinusitis with nasal polyps without bronchial asthma will be administered Mepolizumab (100 MG), subcutaneusly every 30 days
干预措施: Mepolizumab 100 MG [Nucala] (Drug)
结局指标
主要结局
Change in Basement Membrane Thickness
时间窗: through study completion, 156 weeks
The identification of clinical characteristics of non-responders and super-responders. Anwers whether change basement membrane thickness can predict therapeutic response of mepolizumab among patients.
Change in smooth muscle cell mass
时间窗: through study completion, 156 weeks
The identification of clinical characteristics of non-responders and super-responders. Anwers whether change in smooth muscle cell mass can predict therapeutic response of mepolizumab among patients.
Change in microbiome
时间窗: through study completion, 156 weeks
Answers whether there is a microbiome signature at baseline that can predict therapeutic response of mepolizumab among patients. The identification of clinical characteristics of non-responders and super-responders.
次要结局
- Change of cytokine and protein levels in serum(through study completion, 156 weeks)
- Change in exacerbation rate(through study completion, 156 weeks)
- Change of cytokine and protein levels in bronchial washing(through study completion, 156 weeks)
- Change in requiring surgery(through study completion, 156 weeks)
研究者
Associate Prof Konstantinos Porpodis
Associate Professor of Pulmonology
Aristotle University Of Thessaloniki