A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of N91115 for Efficacy and Safety in Patients With CF Heterozygous for F508del-CFTR + Gating Mutation Being Treated With Ivacaftor
试验速览
- 阶段
- 2 期
- 入组人数
- 19
- 试验地点
- 12
- 主要终点
- The absolute change in ppFEV1 in the N91115 treated group
研究概览
简要总结
Cavosonstat (N91115) is being studied as a potential novel therapy for cystic fibrosis (CF), and this study assesses a target population of patients who are heterozygous for F508del-CFTR and a gating mutation that is approved for treatment with ivacaftor (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R).
详细描述
Assess the effect of Cavosonstat (N91115) on lung function when added to preexisting treatment with ivacaftor in adult patients with CF who are heterozygous for F508del-CFTR and a gating mutation that is approved for treatment with ivacaftor (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R).
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
- Triple (Participant, Care Provider, Investigator)
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, heterozygous for F508del-CFTR and a gating mutation that is approved for treatment with ivacaftor (G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, or S549R)
- •Have been treated with chronic ivacaftor twice daily for at least 6 months prior to Screening (date of consent) and are currently being treated with commercially available Ivacaftor
- •Negative serum pregnancy test
- •Weight ≥ 40 kg at screening
- •Oxygen saturation by pulse oximetry ≥ 90% breathing ambient air, at screening
排除标准
- •Any acute infection, including acute upper or lower respiratory infections and pulmonary exacerbations that require treatment that has completed within 2 weeks of Study Day 1 or hospitalization discharge within 2 weeks of Study Day 1
- •Recent infection (per investigator discretion) with organisms associated with more rapid decline in pulmonary status, for example: Burkholderia cenocepacia, Burkholderia dolosa, and Mycobacterium abscessus
- •Any change in the regimen for chronic therapies for CF lung disease (e.g., Pulmozyme®, hypertonic saline, Azithromycin, TOBI®, Cayston®) within 4 weeks of Study Day 1
- •Blood hemoglobin < 10 g/dL at screening
- •Serum albumin < 2.5 g/dL at screening
- •Abnormal liver or renal function
- •History of ventricular tachycardia or other clinically significant ventricular arrhythmias
- •History, including the screening assessment, of prolonged QT and/or QTcF (Fridericia's correction) interval (> 450 msec for men; > 470 msec for women)
- •History of solid organ or hematological transplantation
- •History of alcohol abuse or drug abuse (including cannabis, cocaine, and opioids) in the year prior to screening
- •Use of continuous (24 hr/day) or nocturnal supplemental oxygen
研究组 & 干预措施
Placebo
Matching capsule (BID administration Q12H)
干预措施: Placebo (Drug)
Cavosonstat (N91115) 400 mg
Cavosonstat (N91115) at 400 mg dose (100 mg x 4 capsules) (BID administration Q12H)
干预措施: Cavosonstat (Drug)
结局指标
主要结局
The absolute change in ppFEV1 in the N91115 treated group
时间窗: Baseline, week 4 and 8 assessments
Forced Expiratory Volume (FEV) absolute measurements comparing baseline to after 4 and 8 weeks of N91115 treatment. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. ppFEV1 (predicted for age, gender, and height) is calculated using the Hankinson method.
次要结局
- The relative change from study baseline within the active treatment group in ppFEV1 values(Baseline, week 4 and 8 assessments)
- Absolute change from study baseline within the active treatment group in sweat chloride(Baseline, week 4 and 8 assessments)
- Changes in the respiratory domain of the Cystic Fibrosis Questionnaire - Revised, (CFQ-R)(Baseline, week 4 and 8 assessments)
- Absolute change from baseline within the active treatment group in Patient Global Impression of Change(Baseline, week 4 and 8 assessments)
- Safety as determined by adverse events assessment(Baseline to 8 weeks treatment with a 28-day follow up period)
- Pharmacokinetic Assessment of Maximum Plasma Concentration [Cmax] for N91115 & ivacaftor(Weeks 1, 4 and 8)
- Pharmacokinetic Assessment of area under the plasma concentration verse time curve [AUC] for N91115 & ivacaftor(Weeks 1, 4 and 8)