Open-Label, Exploratory Study to Evaluate the Effects of QR-010 on Nasal Potential Difference in Subjects With CF With the ΔF508 CFTR Mutation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 5
- 主要终点
- Intra-subject Change From Baseline of CFTR-mediated Total Chloride Transport as Measured by Nasal Potential Difference (NPD).
研究概览
简要总结
Exploratory proof of concept study to determine whether intranasal administration of QR-010 in subjects with cystic fibrosis, homozygous or compound heterozygous for the ΔF508 mutation, can increase the function of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR).
详细描述
This is an open-label, multi-center, exploratory study to estimate the effect of intranasal administration of QR-010 on the nasal mucosa in the restoration of CFTR function, as measured by nasal potential difference (NPD), in the nasal epithelium of adult subjects with CF who are homozygous or compound heterozygous for the ΔF508 CFTR mutation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
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
- •Confirmed diagnosis of CF as defined by iontophoretic pilocarpine sweat chloride test (sweat chloride) of > 60 mmol/L
- •Nasal potential difference (NPD) measurement at Screening consistent with CF
- •Confirmation of CFTR gene mutations homozygous or compound heterozygous for the ΔF508 mutation
- •Body mass index (BMI) of ≥ 18 kg/m2
- •Non-smoking for a minimum of 2 years
- •Stable lung function
- •FEV1 ≥40% of predicted normal for age, gender, and height at Screening
排除标准
- •Breast-feeding or pregnant
- •Acute allergy or infection affecting nasal conditions not resolved within 14 days prior Screening
- •Use of lumacaftor or ivacaftor
- •Use of any investigational drug or device
- •Hemoptysis
研究组 & 干预措施
ΔF508 Homozygous
QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks.
干预措施: QR-010 (Drug)
ΔF508 Compound Heterozygous
QR-010 administered intranasally as an atomized liquid 10 mg (5 mg per nostril), 3 times weekly for 4 weeks.
干预措施: QR-010 (Drug)
结局指标
主要结局
Intra-subject Change From Baseline of CFTR-mediated Total Chloride Transport as Measured by Nasal Potential Difference (NPD).
时间窗: Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.
The primary endpoint was the within-subject change from baseline in total chloride transport as measured by NPD, after the Chloride-free+isoproterenol solution (Cl-free+iso), and was based on the average measurements of both nostrils. To provide baseline stability, baseline was defined as the average of the two most recent pre-dose values, where each pre-dose value was the average of two nostrils. A negative change from baseline of Cl-free+iso shows an improvement.
次要结局
- Number of Subjects Experiencing Serious Adverse Events From Baseline Through End of Study.(3 weeks post-treatment.)
- The Mean Change in CFTR-mediated Total Chloride Transport.(2 and 4 weeks, and at 3 weeks post-treatment.)
- Number of Subjects With Abnormalities of Laboratory Parameters From Baseline Through End of Study.(3 weeks post-treatment.)
- Number of Subjects With a -6.6 mV or More Negative Change in CFTR-mediated Total Chloride Transport, and After Different Treatment Durations From Baseline Through End of Study.(2 and 4 weeks, and at 3 weeks post-treatment.)
- Number of Subjects With a -4 mV or More Negative Change in CFTR-mediated Total Chloride Transport, and After Different Treatment Durations From Baseline Through End of Study.(2 and 4 weeks, and at 3 weeks post-treatment.)
- Intra-subject Change of Sodium Transport as Measured by Nasal Potential Difference (NPD) From Baseline Through End of Study.(Baseline, at 2 and 4 weeks, and at 3 weeks post-treatment.)
- Number of Subject Discontinuations Due to AEs From Baseline Through End of Study.(3 weeks post-treatment.)
- Number of Subjects With Abnormalities of Vital Signs & Oximetry From Baseline Through End of Study.(3 weeks post-treatment.)
- Number of Subjects With Abnormalities of Physical Examinations From Baseline Through End of Study.(3 weeks post-treatment.)
- Changes in Nasal Symptoms (Based on the Nasal Examination Rating Scale - NERS) From Baseline Through End of Study.(3 weeks post-treatment.)
- Changes in Nasal Symptoms (Sino-Nasal Outcome Test - SNOT-22) From Baseline Through End of Study.(3 weeks post-treatment.)