NAsal Polyps: Inflammatory & Molecular Phenotyping of Responders to Benralizumab
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Significant reduction of the Nasal polyps Score (range: 0-8; higher values mean larger nasal polyps size)
研究概览
简要总结
Background and rationale:
Phase III-b study.
Population and patient selection criteria: Adult patients with Chronic Rhinosinusitis with Nasal Polyps (allergic and non-allergic) requiring at least 1000 mg oral prednisone over the previous twelve months to control symptoms of rhinosinusitis, and with:
- Nasal polyps score (Meltzer et al.) ≥ 5
- Symptoms VAS scores (for nasal obstruction, hyposmia, post-nasal drip, sneezing, rhinorrea; 0-10 for each symptom) > 24 Sample size: 20 subjects.
Study design and study duration:
This is a pilot, prospective, double-blind placebo-controlled (DBPC) phase III-b trial with Benralizumab 30 mg administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks, for a treatment-period of 16 weeks (followed up at 32 and 52 weeks) in patients with chronic rhinosinusinusitis with nasal polyps (CRSwNP).
Description of study treatment/product/intervention: Benralizumab, 30 mg subcutaneously every 4 week for the first 3 doses, and then every 8 weeks.
Objectives:
- Primary objective: To assess the clinical efficacy of Benralizumab on CRSwNP at week 24 (vs baseline) after the beginning of treatment, and to correlate the presence of baseline biomarkers with nasal polyp (NP) score improvement, in order to identify any possible predictive biomarker of response to Benralizumab.
- Secondary objective: In the follow up phase we will monitor all the biomarkers at 32 and 52 weeks , this monitoring will ascertain if any of those will predict relapse of nasal polyps and consequently when Benralizumab treatment has to be reinstalled.
- Safety objective: To evaluate the safety and tolerability of Benralizumab in patients with CRSwNP
Statistical methods, data analysis: Descriptive analysis of all collected variables at all time-points will be performed. Patients will be classified into "responders" and "non responders", for primary endopoint variable. Continuous variables will be evaluated with the normality test of Kolmogorov-Smirnov and compared with ANOVA or the Mann-Whitney test, depending on the normality of distribution. Categorical variables will be compared using Fisher's exact test.
Ethical considerations: The study will be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and are consistent with ICH/Good Clinical Practice, applicable regulatory requirements and the Sponsor policy on Bioethics and Human Biological Samples.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Investigator)
盲法说明
Randomization will occur by assigning a unique sequential study code to a balanced number of randomly assorted treatment vials.
An online open source randomization software will be used to assign treatment groups, and this will be done by an external person from those who will follow and treat the patients.
Patients randomization will be blinded to the patients themselves and to all the personnel that will have contact with them during the trial
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 with Chronic Rhinosinusitis with Nasal Polyps (allergic and non-allergic) requiring at least 1000 mg oral prednisone over the previous twelve months to control symptoms of rhinosinusitis, and with:
- •Nasal polyps score (Meltzer et al.) > 5
- •Symptoms VAS scores (for nasal obstruction, hyposmia, post-nasal drip, sneezing, rhinorrea; 0-10 for each symptom) > 24
- •Provision of informed consent prior to any study specific procedure
排除标准
- •Patients < 18 years age
- •Pregnant women
- •Biologic therapy in the past 6 months (or at least a period corresponding to 5 half-life of used drugs) (eg: omalizumab, mepolizumab, reslizumab, dupilumab)
- •Previous treatment with Benralizumab
- •Known hypersensitivity to benralizumab or any of its excipients
- •Immunosuppression other than oral steroids in the past 3 months
- •Allergen immunotherapy in the past 6 months
- •Serious life threatening cardiopulmonary disorders
- •Systemic immunologic disorder in the last 12 months
- •Positive history for malignant tumors ever in patient's life
- •Patients with conditions or concomitant diseases making them non evaluable at visit 1 or for the primary efficacy endpoint:
- •Ongoing rhinitis medicamentosa
- •Nasal septal deviation occluding at least one nostril
- •Acute sinusitis, nasal infection, upper respiratory infections
- •Radiologic suspicion or confirmed invasive or expansive fungal rhinosinusitis
- •Eosinophilic Granulomatosis with Polyangiitis (previously named Churg-Strauss Syndrome)
- •Granulomatosis with Polyangiitis (previously named Wegener's granulomatosis)
- •Young's Syndrome
- •Kartagener's Syndrome
- •all ciliary dyskinesia
- •Cystic Fibrosis
- •Systemic corticosteroid treatment for other chronic conditions (i.e.: autoimmune disorders, tumors,....)
- •Evidence of active systemic immunedepression (i.e..: primary or secondary immunodeficiency)
- •Patients with severe asthma, defined according to ERS/ATS definition
研究组 & 干预措施
Benralizumab
Benralizumab 30 mg administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks, for a treatment-period of 16 weeks
干预措施: Benralizumab (Biological)
Placebo
Placebo administered subcutaneously every 4 weeks for the first 3 doses and then every 8 weeks, for a treatment-period of 16 weeks
干预措施: Placebo (Biological)
结局指标
主要结局
Significant reduction of the Nasal polyps Score (range: 0-8; higher values mean larger nasal polyps size)
时间窗: at week 24 (vs baseline)
score reduction of 1.5
次要结局
- Improvement of smell Visual Analogue Scale (VAS; range: 0-10; higher values mean worse smell)(at week 24 (vs baseline))
- Reduction in Lund-MacKay Score (range: 0-24; higher values mean larger nasal polyps extension)(at week 24 (vs baseline))
- Improvement of Sino-Nasal Outcome Test (SNOT-22; range: 0-110; higher values mean poorer disease-related quality of life)(at week 24 (vs baseline))