Riley Hospital for Children at IU Health, Indiana University School of Medicine, Indianapolis, IN, USA.
Medical University of South Carolina, Charleston, SC, USA.
J Cyst Fibros. 2021 Jan;20(1):78-85. doi: 10.1016/j.jcf.2020.09.008. Epub 2020 Oct 1.
Few therapies specifically address the chronic airway inflammation in cystic fibrosis (CF) that contributes to progressive destruction of lung tissue and loss of lung function. Lenabasum is a cannabinoid type 2 receptor (CB2) agonist that resolves inflammation in a number of in vitro and in vivo models.
A Phase 2 double-blind, randomized, placebo-controlled study assessed the safety and tolerability of lenabasum in adults with CF. Subjects with FEV% (ppFEV) ≥40% predicted were randomized to lenabasum 1 or 5 mg or placebo once daily (QD) (Weeks 1-4), then 20 mg QD, 20 mg twice daily (BID) or placebo (Weeks 5-12), with follow-up at Week 16. Pulmonary exacerbations (PEx) were recorded and biomarkers of blood and lung inflammation were measured.
Of 89 subjects randomized, 51 lenabasum and 23 placebo-only subjects completed the study. No deaths or serious or severe adverse events (AE) were considered related to lenabasum. Most AEs were mild/moderate, and the most common were PEx, hemoptysis, dry mouth, and upper respiratory infection. Three lenabasum and one placebo-only subjects discontinued the study for a treatment related AE. New PEx were treated with intravenous antibiotics in 4.0% of lenabasum-treated vs. 11.4% of placebo-treated subjects, during Weeks 1-4 and 5.2% compared to 13.0% during Weeks 5-12 (p<0.2). No significant differences in ppFEV1 were observed between treatment groups. Sputum neutrophils, eosinophils, and neutrophil elastase were numerically reduced, and significant (p<0.05) reductions in IL-8 and immunoglobulin G levels occurred with lenabasum.
The safety findings of lenabasum, coupled with biomarker data, support further testing in a larger study with a longer duration.
很少有疗法专门针对囊性纤维化 (CF) 中的慢性气道炎症，而这种炎症会导致肺组织的进行性破坏和肺功能的丧失。Lenabasum 是一种大麻素 2 型受体 (CB2) 激动剂，可在多种体外和体内模型中缓解炎症。
一项 2 期、双盲、随机、安慰剂对照研究评估了 lenabasum 在 CF 成人中的安全性和耐受性。FEV%（ppFEV）≥40%预测值的受试者被随机分配接受 lenabasum 1 或 5mg 或安慰剂，每天一次（QD）（第 1-4 周），然后接受 20mg QD、20mg 每日两次（BID）或安慰剂（第 5-12 周），第 16 周进行随访。记录肺部恶化（PEx）情况，并测量血液和肺部炎症的生物标志物。
在 89 名随机分组的受试者中，51 名 lenabasum 组和 23 名仅接受安慰剂组完成了研究。没有死亡或严重或严重不良事件（AE）被认为与 lenabasum 有关。大多数 AE 为轻度/中度，最常见的是 PEx、咯血、口干和上呼吸道感染。3 名 lenabasum 组和 1 名仅接受安慰剂组因治疗相关 AE 而退出研究。在第 1-4 周和第 5 周，静脉用抗生素治疗新出现的 PEx 的 lenabasum 组受试者比例为 4.0%，安慰剂组为 11.4%，第 5-12 周分别为 5.2%和 13.0%（p<0.2）。治疗组之间 ppFEV1 无显著差异。痰中性粒细胞、嗜酸性粒细胞和中性粒细胞弹性蛋白酶数值降低，IL-8 和免疫球蛋白 G 水平显著降低（p<0.05）。
lenabasum 的安全性发现，加上生物标志物数据，支持在更大规模、更长时间的研究中进一步测试。
