Opening the "Black Box" on Tezepelumab's Effect on Chronic Rhinosinusitis With Severe Asthma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 10
- 主要终点
- Eosinophil Count
研究概览
简要总结
The study explores how chronic rhinosinusitis (CRS) and asthma share a common inflammatory process, particularly affecting patients with both conditions. Interaction between immune cells (Interleukins) and Th2 cytokines, such as TSLP, exacerbates asthma control in CRS patients, especially those with nasal polyps (CRSwNP). TSLP plays a pivotal role in initiating and maintaining airway inflammation in both diseases. Tezepelumab, a biologic therapy targeting TSLP, shows promise in reducing inflammation markers in severe asthma but its impact on CRSwNP and quality of life remains unclear. The study proposes investigating Tezepelumab's efficacy in treating CRSwNP and severe asthma to inform future biologic therapies.
详细描述
The investigators hypothesize that TSLP blockade with Tezepelumab will a) reduce upper airway inflammation based on histological, inflammatory, and remodeling biomarkers, that are evident in the airway remodeling process and b) correlate to a positive clinical response. Thus, nasal samples from chronic rhinosinusitis with nasal polyps (CRSwNP) patients with Severe Asthma (SA) pre- and post-treatment will exhibit inflammatory biomarkers and histopathological evidence that could prove responsive to the Tezepelumab.
The overall research objectives are to evaluate the effect of study intervention (Tezepelumab) on CRSwNP-SA outcomes through a) evaluating the sinonasal inflammatory profile, histopathological features, and remodeling biomarkers and b) investigating the impact of Tezepelumab on the CRSwNP-related clinical outcomes in the treated study subjects.
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
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be ≥19 of age at the time of signing the informed consent form
- •Capable of giving signed informed consent.
- •Having CRSwNP based on clinical symptoms and/or radiographic or endoscopic evidence of inflammation in their upper airways (Diagnosis consistent with EPOS 2020)(2)and severe asthma:
- •SA based on GINA criteria (37) and confirmed with spirometry and assessmenton the previous history of asthma (a pre-post bronchodilator spirometry ormethacholine challenge to document the positive or negative history of asthmawill be performed if there is no clinical record).
- •Nasal polyp score (NPS) of at least 2 on each side
- •Females of childbearing potential must commit using an acceptable method of birthcontrol for the duration of the study and they must have a negative urine pregnancy test ateach study visit
- •Not expecting to have surgery within the next 7 months
排除标准
- •Have previously undergone sinus surgery or nasal polypectomy
- •A history of organ transplantation such as lung transplantation
- •Previously or currently using immunomodulator medications or antihistamines
- •A history of auto-immune diseases
- •Current or past sinonasal or bronchial tumors
- •Currently using systemic or oral corticosteroids
- •Women who are pregnant, plan to become pregnant, or breastfeed during the trial
- •Current participation in any other interventional treatment trials
- •Compliance: is unlikely to comply with study visits based on investigator judgment:
- •Diagnosed or suspected malignant or premalignant nasal disease (e.g. SchniderianPapilloma, unilateral nasal polyposis)
- •Fungal rhinosinusitis (CT/Histology), positive Aspergillus skin prick testing and/orpositive Aspergillus IgE RAST (Radioallergosorbent) testing
- •Malignant neoplasm within 5 years (from screening) excluding basal cell or squamouscell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterinecervix treated locally and without metastatic disease for 3 years.
- •Active bleeding disorders, and/or inability to support interruption to anticoagulant or anti-platelet therapies for nasal biopsy.
- •Severe nasal deformity precluding endoscopic assessment/biopsy of postnasal space
- •Have an acute or chronic infection (excluding that related to CRS) requiring managementas follows:
- •Currently on any treatment for a chronic infection such as pneumocystis,cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria
- •Hospitalisation solely for the treatment of proven infection requiring parenteral (IV orIM) antibiotics (antibacterial, antiviral, antifungal, or anti-parasitic agents) within 60days of Day 1
- •Proven severe infection requiring outpatient treatment with parenteral (IV or IM)antibiotics (antibacterial, antiviral, antifungal, or anti-parasitic agents) within 60 daysof Day
- •Prophylactic anti-infective treatment is allowed.
- •Known positive human immunodeficiency virus (HIV) status
- •Known positive Hepatitis B (HB) or Hepatitis C status
- •Have clinical evidence of significant unstable or uncontrolled acute or chronic diseaseswhich, in the opinion of the principal investigator, could confound the results of the study orput the participant at undue risk
- •Have a planned surgical procedure, laboratory abnormality, or condition that, in theopinion of the principal investigator, makes the participant unsuitable for the study.
- •Have received any investigational agent (that is not approved for sale in Canada) within60 days of Day 1
- •Smoking history; current or former smokers with a smoke history of packs year >15
- •Subjects with parasitic (helminthic) infection
- •Subjects with hypersensitivity; with allergy/intolerance to a monoclonal antibody or biologics
- •Subjects allergic to Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs)
研究组 & 干预措施
Tezepelumab
Tezepelumab 210 mg subcutaneous injection every 4 weeks to all 10 participants
干预措施: Tezepelumab (Biological)
结局指标
主要结局
Eosinophil Count
时间窗: From baseline to 24 weeks
Measurement of eosinophil count in tissue samples. Cells per high power field (HPF) or cells per millimeter squared (cells/mm²).
Neutrophil count
时间窗: From baseline to 24 weeks.
Measurement of neutrophil count in tissue samples. Cells per high power field (HPF) or cells per millimeter squared (cells/mm²).
Basement Membrane Thickness
时间窗: From baseline to 24 weeks
Measurement of the thickness of the basement membrane in tissue samples. Micrometers (µm)
Fibrosis
时间窗: From baseline to 24 weeks
Assessment of the extent of fibrosis in tissue samples, which may involve scoring systems or quantitative measurements
Squamous Metaplasia
时间窗: From baseline to 24 weeks
Immunohistochemical staining will be used to identify the presence of squamous metaplasia, with scoring based on percentage of positive cells.
Lymphocytic Proliferation
时间窗: From baseline to 24 weeks
Lymphocytic proliferation will be assessed using immunohistochemistry (IHC) to measure the Ki-67 proliferation index in tissue samples, specifically identifying the percentage of Ki-67-positive lymphocytes
次要结局
- Immunoglobulin leves(24 weeks)
- Th2 Cytokines(24 weeks)
- Th1/Th17 Cytokines(24 weeks)
- Myeloperoxidase (MPO)(24 weeks)
- Interferon-γ (IFN-γ)(24 weeks)
- SNOT-22 (Sino-Nasal Outcome Test 22-item)(24 weeks)
- Health-Related Quality of Life(24 weeks)
- Asthma Control Questionnaire(24 weeks)
- Epithelial Changes(24 weeks)
- Modified Lund-Kennedy Endoscopy Score(24 weeks)
- Lund-Mackay CT Scan Score(24 weeks)
- Changes in smell(24 weeks)
研究者
Dr. Andrew Thamboo, MD
Clinical Assistant Professor
St. Paul's Sinus Centre