A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Dose Escalation Study of N6022 to Evaluate Safety and Pharmacokinetics in Subjects With Cystic Fibrosis Homozygous for the F508del-CFTR Mutation (SNO1)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 17
- 主要终点
- Safety and Tolerability
研究概览
简要总结
The purpose of this study is to investigate the safety, tolerability and pharmacokinetics of N6022, and to obtain descriptive information on the effect of N6022 on biomarkers of CFTR function and inflammation in adult cystic fibrosis subjects who are homozygous for the F508del-CFTR mutation.
详细描述
This is a double-blind, randomized, placebo-controlled, multicenter, sequential dose-escalation study which will occur in two parts. All selection criteria, assessments and procedures described in this protocol will be applied to both parts. Up to 5 cohorts will be studied with a total of 67 patients at approximately 18 clinical sites in the United States.
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
- Quadruple (Participant, Care Provider, Investigator, 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
- •Homozygous for F508del-CFTR gene
- •Sweat chloride ≥ 60 mEq/L by quantitative pilocarpine iontophoresis
- •Body weight ≥ 40 kg
- •FEV1 ≥ 40% predicted
- •Oxygen saturation ≥ 90% breathing ambient air
- •Hematology and clinical chemistry of blood and urine results with no clinically significant abnormalities that would interfere with the study assessments
- •Negative pregnancy test for women of child bearing potential
- •Sexually active subjects of child bearing potential willing to follow contraception requirements
排除标准
- •Previous enrollment in another cohort for this study.
- •Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment within 4 weeks of Study Day
- •Any change in chronic therapies for CF lung disease within 4 weeks of Study Day
- •Blood hemoglobin <10 g/dL at screening.
- •Serum albumin <2.5 g/dL at screening.
- •Abnormal liver function defined as ≥ 3 x upper limit of normal (ULN) in three or more of the following: AST, ALT, GGT, ALP, total bilirubin at screening.
- •History of abnormal renal function (creatinine clearance < 50 mL/min using Cockcroft-Gault equation) within a year at screening.
- •History, including the screening assessment, of ventricular tachycardia or other ventricular arrhythmias.
- •History, including the screening assessment, of prolonged QT and/or QTcF interval (> 450 msec).
- •History of solid organ or hematological transplantation.
- •Intranasal medication changes within 14 days prior to Study Day 1
- •Required Use of continuous (24 hr/d) or nocturnal supplemental oxygen.
- •Concomitant use of any inhibitors or inducers of CYP3A4.
研究组 & 干预措施
N6022
Subjects randomized to study drug will receive N6022 by intravenous infusion once per day for 7 days
干预措施: N6022 (Drug)
Normal saline
Subjects randomized to placebo will receive normal saline administered intravenously using the same volume as the active drug group
干预措施: Normal saline (Drug)
结局指标
主要结局
Safety and Tolerability
时间窗: Over 7 treatment days and 7 days of follow-up
Assessments are based on numbers of subjects with abnormal clinical evaluations, abnormal laboratory assessments, and adverse events.
次要结局
- Change in Biomarkers of CFTR Function(Change from baseline at Day 7)
- Change in Percent Predicted Forced Expiratory Volume in 1 Second (FEV1)(Change from baseline at Day 7)