Safety and Preliminary Efficacy of Dexpramipexole in Patients With Chronic Sinusitis With Nasal Polyps and Eosinophilia (CSNP-E)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 20
- 试验地点
- 7
- 主要终点
- Ratio to Baseline in Peripheral Blood Eosinophil Counts After 6 Months of Treatment
研究概览
简要总结
Phase 2, open-label, multi-center study to evaluate the clinical effects of oral administration of dexpramipexole for 6 months in subjects with chronic sinusitis with nasal polyps and eosinophilia.
详细描述
This open-labelled study will evaluate the safety and preliminary efficacy of dexpramipexole for reducing the number of eosinophils in the peripheral blood and in improving nasal polyp score when administered to 20 subjects with chronic sinusitis with nasal polyps and eosinophilia.
Subjects will received dexpramipexole for up to 6 months and will have safety tests performed monthly and will have efficacy evaluations performed at month 1, month 3, and month 6 after beginning study drug.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female >18 or <70 years of age
- •Willing to practice effective contraception during the study and be willing and able to continue contraception for 1 month (females) or 3 months (males) after the last dose of study treatment
- •Confirmed diagnosis of chronic sinusitis with nasal polyps
- •Documented history of nasal eosinophilia
- •Documented peripheral absolute eosinophil count >300 cells/μL
- •Bilateral total polyp score of >4
- •Sino-nasal outcome test (SNOT-22) score of >7
- •Using an intranasal corticosteroid spray or irrigation (< 1000 μg/day beclomethasone or equivalent)
排除标准
- •Acute sinusitis, concurrent nasal infection, or subjects who have had a nasal or upper respiratory tract infection within 2 weeks prior to baseline
- •CT scan suggestive of allergic fungal rhinosinusitis
- •Nasal septal deviation that would occlude at least one nostril
- •Nasal surgery (including polypectomy) within 6 months prior to baseline
- •History of more than 5 sinonasal surgeries requiring general anesthesia
- •History of more than 2 sinonasal surgeries that changed the lateral wall of the nose
- •History of cystic fibrosis, primary ciliary's dysfunction or Kartagener's syndrome
- •History of diagnosis with a parasitic infection
- •Hospitalization or emergency treatment for the treatment of asthma two or more times in the 12 months prior to baseline
- •Hospitalization for an acute asthmatic attack within 4 weeks prior to baseline
- •Forced expiratory volume (FEV1) of <60% of predicted normal range
- •Treatment with a systemic corticosteroid or intra-polyp corticosteroid within 8 weeks prior to baseline or anticipated need for systemic corticosteroids during the study treatment period
- •Utilization of rescue oral corticosteroids for asthma or chronic sinusitis exacerbation more than one time within the past 1 year
- •Treatment with an investigational drug in the previous 30 days or 5-half-lives, whichever is longer
- •Treatment with a monoclonal antibody therapy including omalizumab (Xolair®), within 5-half-lives
- •Treatment with zileuton (Zyflo®) within 4 weeks of baseline
- •Treatment with pramipexole (Mirapex®) within 4 weeks of baseline
- •History of malignancy, including solid tumors and hematologic malignancies (except basal cell and squamous cell cancers of the skin that have been completely excised and cured)
- •History of human immunodeficiency virus (HIV) or hepatitis B or C
- •History of unstable or severe cardiac, hepatic, or renal disease, or other medically significant illness
- •Medical or other condition likely to interfere with subject's ability to undergo study procedures, adhere to visit schedule or comply with study requirements
- •Absolute neutrophil count <2000 cells/μL at screening, or any documented history of neutropenia
- •Total IgE >1500 IU/ml at any visit prior to baseline
- •Renal dysfunction, defined as an estimated glomerular filtration rate (eGFR) of ≤80 mg/dL at screening (estimation of creatinine clearance using the MDRD formula)
- •History of long QT syndrome or arrhythmia
- •Prolongation of QT/QTc interval (e.g., repeated demonstration of a QT/QTc interval >450 ms) at screening or pre-dose on day 1
- •Clinically important abnormalities in resting ECG that may interfere with the interpretation of QTc interval changes at screening or pre-dose on day 1, including any of the following:
- •PR interval >210 ms;
- •QRS >110 ms;
- •Heart rate <45 bpm or >100 bpm (average of 3 assessments).
- •Pregnant women or women breastfeeding
研究组 & 干预措施
dexpramipexole
dexpramipexole 150 mg BID
干预措施: dexpramipexole (Drug)
结局指标
主要结局
Ratio to Baseline in Peripheral Blood Eosinophil Counts After 6 Months of Treatment
时间窗: Baseline and Month 6
Change in peripheral blood eosinophil (measured in cells/μL) from baseline to month 6 is presented as ratio to baseline.
Change From Baseline in Total Polyp Score (TPS) After 6 Months of Treatment
时间窗: Baseline and Month 6
The change in Nasal Polyp Score (NPS) score after 6 months of treatment is presented. A blinded Central Endoscopy Rater determined the NPS for each nare on a scale of 0 to 4, and the bilateral NPS scores were added to generate the Total Polyp Score (TPS) on a scale of 0 to 8. A lower TPS corresponds to a lower polyp burden.
次要结局
- Number of Subjects With Potentially Clinically Significant Values in Vital Signs and Weight(6 months)
- Number of Subjects With Potentially Significant Values in Electrocardiogram Parameters(6 months)
- Number of Subjects With Potentially Clinically Significant Values in Clinical Laboratory Evaluations(6 months)
- Ratio to Baseline in Peripheral Blood Eosinophil Counts After 3 Months of Treatment(Baseline and Month 3)
- Change From Baseline in TPS After 3 Months of Treatment(Baseline and Month 3)