Abstract：
BACKGROUND: Lung inflammation is associated with tissue damage in cystic fibrosis (CF). LAU-7b, a novel oral drug candidate, was shown to control inflammation and stabilize CFTR protein in the epithelial membrane during inflammatory stress in preclinical models of CF.
METHODS: A double-blind, randomized, placebo-controlled Phase 2 study was conducted to evaluate efficacy and safety of LAU-7b in adults with CF. LAU-7b or placebo was administered over 24 weeks as six 21-day treatment cycles each separated by 7 days. The primary efficacy endpoint was the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) at 24 weeks.
RESULTS: A total of 166 subjects received at least one dose of study drug (Intent-To-Treat population, ITT), of which 122 received ≥5 treatment cycles (Per-Protocol population, PP). Both treatment arms showed a mean lung function loss at 24 weeks of 1.18 ppFEV1 points with LAU-7b and 1.95 ppFEV1 with placebo, a 0.77 ppFEV1 (40 s) difference, p=0.345, and a 0.95 ppFEV1 (49 %) difference in the same direction in PP population, p=0.263. Primary analysis of mean ppFEV1 through 24 weeks showed differences of 1.01 and 1.23 ppFEV1, in the ITT (65 % less loss, p=0.067) and PP populations (78 % less loss, reaching statistical significance p=0.049), respectively. LAU-7b had an acceptable safety profile.
CONCLUSIONS: Although the study did not meet its primary efficacy endpoint in the ITT population, LAU-7b was generally well tolerated and showed evidence of preservation of lung function to support further development.
METHODS: A double-blind, randomized, placebo-controlled Phase 2 study was conducted to evaluate efficacy and safety of LAU-7b in adults with CF. LAU-7b or placebo was administered over 24 weeks as six 21-day treatment cycles each separated by 7 days. The primary efficacy endpoint was the absolute change from baseline in percent predicted forced expiratory volume in 1 second (ppFEV1) at 24 weeks.
RESULTS: A total of 166 subjects received at least one dose of study drug (Intent-To-Treat population, ITT), of which 122 received ≥5 treatment cycles (Per-Protocol population, PP). Both treatment arms showed a mean lung function loss at 24 weeks of 1.18 ppFEV1 points with LAU-7b and 1.95 ppFEV1 with placebo, a 0.77 ppFEV1 (40 s) difference, p=0.345, and a 0.95 ppFEV1 (49 %) difference in the same direction in PP population, p=0.263. Primary analysis of mean ppFEV1 through 24 weeks showed differences of 1.01 and 1.23 ppFEV1, in the ITT (65 % less loss, p=0.067) and PP populations (78 % less loss, reaching statistical significance p=0.049), respectively. LAU-7b had an acceptable safety profile.
CONCLUSIONS: Although the study did not meet its primary efficacy endpoint in the ITT population, LAU-7b was generally well tolerated and showed evidence of preservation of lung function to support further development.
摘要：
背景：肺部炎症与囊性纤维化（CF）的组织损伤有关。LAU-7b,一种新型口服药物候选物，在CF的临床前模型中，显示在炎症应激期间控制炎症并稳定上皮膜中的CFTR蛋白。
方法：双盲，随机化，我们进行了安慰剂对照2期研究,以评估LAU-7b在成人CF患者中的疗效和安全性.LAU-7b或安慰剂在24周内作为六个21天治疗周期施用,每个周期间隔7天。主要疗效终点是在24周时1秒内预测的用力呼气量百分比(ppFEV1)相对于基线的绝对变化。
结果：总共166名受试者接受了至少一剂研究药物（意向治疗人群，ITT),其中122人接受了≥5个治疗周期(符合方案的人群，PP).两组治疗组在24周时平均肺功能损失为LAU-7b的1.18ppFEV1点，安慰剂的1.95ppFEV1点，0.77ppFEV1(40s)差异，p=0.345，PP种群中相同方向的0.95ppFEV1（49％）差异，p=0.263。主要分析平均ppFEV1到24周显示1.01和1.23ppFEV1的差异，在ITT（减少65%，p=0.067)和PP群体(损失减少78%，达到统计学意义p=0.049)，分别。LAU-7b具有可接受的安全性。
结论：尽管该研究未达到ITT人群的主要疗效终点，LAU-7b通常具有良好的耐受性，并显示出保留肺功能以支持进一步发展的证据。
方法：双盲，随机化，我们进行了安慰剂对照2期研究,以评估LAU-7b在成人CF患者中的疗效和安全性.LAU-7b或安慰剂在24周内作为六个21天治疗周期施用,每个周期间隔7天。主要疗效终点是在24周时1秒内预测的用力呼气量百分比(ppFEV1)相对于基线的绝对变化。
结果：总共166名受试者接受了至少一剂研究药物（意向治疗人群，ITT),其中122人接受了≥5个治疗周期(符合方案的人群，PP).两组治疗组在24周时平均肺功能损失为LAU-7b的1.18ppFEV1点，安慰剂的1.95ppFEV1点，0.77ppFEV1(40s)差异，p=0.345，PP种群中相同方向的0.95ppFEV1（49％）差异，p=0.263。主要分析平均ppFEV1到24周显示1.01和1.23ppFEV1的差异，在ITT（减少65%，p=0.067)和PP群体(损失减少78%，达到统计学意义p=0.049)，分别。LAU-7b具有可接受的安全性。
结论：尽管该研究未达到ITT人群的主要疗效终点，LAU-7b通常具有良好的耐受性，并显示出保留肺功能以支持进一步发展的证据。
