BACKGROUND 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. METHODS A Phase 2 double-blind, randomized, placebo-controlled study assessed the safety and tolerability of lenabasum in adults with CF. Subjects with FEV1% (ppFEV1) ≥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. RESULTS 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. CONCLUSIONS The safety findings of lenabasum, coupled with biomarker data, support further testing in a larger study with a longer duration.

中文翻译：

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lenabasum 在成人囊性纤维化 2 期随机、安慰剂对照试验中的安全性和有效性

背景 很少有疗法专门针对囊性纤维化 (CF) 中的慢性气道炎症，该炎症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，可在许多体外和体内模型中解决炎症。方法 一项 2 期双盲、随机、安慰剂对照研究评估了 lenabasum 在成人 CF 中的安全性和耐受性。FEV1% (ppFEV1) ≥ 40% 预测值的受试者被随机分配至 lenabasum 1 或 5 mg 或安慰剂每日一次 (QD)（第 1-4 周），然后 20 mg QD、20 mg 每日两次 (BID) 或安慰剂（第 5 周） -12)，在第 16 周进行随访。记录肺病恶化 (PEx) 并测量血液和肺部炎症的生物标志物。结果 89 名受试者随机分组，51 名 lenabasum 和 23 名安慰剂受试者完成了这项研究。没有死亡或严重或严重不良事件 (AE) 被认为与 lenabasum 相关。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。三名 lenabasum 和一名仅服用安慰剂的受试者因治疗相关 AE 停止研究。在第 1-4 周和 5.2% 的 lenabasum 治疗受试者中，4.0% 和 11.4% 的安慰剂治疗受试者接受静脉注射抗生素治疗新 PEx，而第 5-12 周则为 13.0%（p<0.2）。在治疗组之间未观察到 ppFEV1 的显着差异。痰中性粒细胞、嗜酸性粒细胞和中性粒细胞弹性蛋白酶在数值上降低，并且使用lenabasum 时IL-8 和免疫球蛋白G 水平显着降低（p<0.05）。