Phase 1b, Randomized, Double-blind, Placebo-controlled, Dose Escalation Study to Evaluate the Safety, Tolerability and Pharmacokinetics of QR-010 in Subjects With Homozygous ΔF508 Cystic Fibrosis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 27
- 主要终点
- Incidence of Subjects Experiencing Dose-Limiting Toxicities (DLT) in Each Dose Cohort From Baseline Through End of Study Visit.
研究概览
简要总结
A randomized, double-blind, placebo-controlled study of single and multiple ascending doses of QR-010 in adults homozygous for ΔF508 Cystic Fibrosis.
详细描述
The purpose of this study is to evaluate the safety, tolerability, and to determine the pharmacokinetics of QR-010 administered via inhalation in adult homozygous for ΔF508 Cystic Fibrosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（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
- •Confirmation of CFTR gene mutations homozygous for the ΔF508 mutation
- •Body mass index (BMI) ≥ 17 kg/m2
- •Non-smoking for a minimum of two years
- •FEV1 ≥70% of predicted normal for age, gender, and height, at Screening
- •Stable lung function
- •Adequate hepatic and renal function
排除标准
- •Breast-feeding or pregnant
- •Use of lumacaftor or ivacaftor
- •Use of any investigational drug or device
- •History of lung transplantation
- •Hemoptysis
研究组 & 干预措施
QR-010
QR-010 administered via inhalation either as a single dose or three times weekly for four weeks.
干预措施: QR-010 (Drug)
Placebo
Placebo (normal saline) administered via inhalation either as a single dose or three times weekly for four weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Incidence of Subjects Experiencing Dose-Limiting Toxicities (DLT) in Each Dose Cohort From Baseline Through End of Study Visit.
时间窗: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
DLT's were defined as an allergic reaction, acute bronchospasm or acute AEs of interest requiring (immediate) medical intervention.
Severity of Treatment Emergent Adverse Events From Baseline Through End of Study
时间窗: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Assessment of severity of treatment emergent adverse events (TEAEs). Severity is graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events Modified for CF (CTCAE v4.03). For events not present in this listing the following grading was applied: Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated; Moderate: Minimal, local, or noninvasive intervention indicated; discomfort sufficient to reduce or interfere with daily activities; Severe: Medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization may be indicated; disabling; limits self-care with significant interference with daily activities; incapacitating with inability to perform self care activities of daily living; Life-threatening: Urgent intervention indicated; immediate risk of death.
Incidence of Subjects Experiencing Treatment Emergent Adverse Events From Baseline Through End of Study
时间窗: 8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts
Number of subjects experiencing at least one treatment emergent adverse events (TEAEs)
次要结局
- Time to Maximum Serum Concentration(8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts)
- Area Under the Curve to Infinity [AUC(0-∞)](8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts)
- Number of Subjects With Abnormalities Reported Regarding Laboratory Parameters, Vital Signs, ECG, Spirometry, and Physical Findings.(8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts)
- Maximum Serum Concentration(8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts)
- Terminal Half-life (T1/2)(8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts)
- Area Under the Curve to Final Sample [AUC(0-last)](8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts)
- Serum Clearance (CL)(8 Days for Single-dose cohorts; 8 weeks for Multiple-dose cohorts)