未经证实:Efruxifermin已在非酒精性脂肪性肝炎(NASH)和F1-F3纤维化患者中显示出临床疗效。BALANCED队列C的主要目的是评估代偿性NASH肝硬化患者使用依fruxifermin的安全性和耐受性。
UNASSIGNED:将NASH和4期纤维化患者(n=30)随机分为2:1,每周一次接受Efruxifermin50mg(n=20)或安慰剂(n=10),共16周。主要终点是依fruxifermin的安全性和耐受性。次要和探索性终点包括评估肝损伤和纤维化的非侵入性标志物,葡萄糖和脂质代谢,部分同意接受研究结束肝活检的患者的组织学变化。
UNASSIGNED:Efruxifermin安全且耐受性良好;大多数不良事件(AE)为1级(n=7,23.3%)或2级(n=19,63.3%)。最常见的AE是胃肠道,包括瞬态,轻度至中度腹泻,和/或恶心。在肝损伤(丙氨酸氨基转移酶)以及葡萄糖和脂质代谢的关键标志物中发现了显着改善。efruxifermin治疗16周与包括Pro-C3在内的非侵入性纤维化标志物的显着减少相关(从基线[LSMCFB]-9μg/Lefruxiferminvs.-3.4μg/L安慰剂;p=0.0130)和ELF评分(-0.4efruxiferminvs.+0.4安慰剂;p=0.0036),具有降低肝脏硬度的趋势(LSMCBB-5.7kPaefruxifermin与-1.1kPa安慰剂;n.s.)。在16周后接受肝活检的12名依弗西敏治疗的患者中,4(33%)实现了至少一个阶段的纤维化改善,而NASH没有恶化,而另外3人(25%)获得了NASH的分辨率,与5例安慰剂治疗患者中的0例相比。
未经证实:Efruxifermin表现出安全和良好的耐受性,在肝损伤标志物方面有令人鼓舞的改善,纤维化,和糖和脂质代谢后16周的治疗,保证在更大和更长期的研究中得到证实。
未经批准:非酒精性脂肪性肝炎(NASH)引起的肝硬化,非酒精性脂肪性肝病的进行性形式,代表了重大的未满足的医疗需求。目前没有批准的用于治疗NASH的药物。这个概念证明是随机的,双盲临床试验表明,在NASH肝硬化患者中,与安慰剂相比,依弗西汀治疗具有潜在的治疗益处.
未经评估:NCT03976401。
UNASSIGNED: Efruxifermin has shown clinical efficacy in patients with non-alcoholic steatohepatitis (NASH) and F1-F3 fibrosis. The primary objective of the BALANCED Cohort C was to assess the safety and tolerability of efruxifermin in patients with compensated NASH cirrhosis.
UNASSIGNED: Patients with NASH and stage 4 fibrosis (n = 30) were randomized 2:1 to receive efruxifermin 50 mg (n = 20) or placebo (n = 10) once-weekly for 16 weeks. The primary endpoint was safety and tolerability of efruxifermin. Secondary and exploratory endpoints included evaluation of non-invasive markers of liver injury and fibrosis, glucose and lipid metabolism, and changes in histology in a subset of patients who consented to end-of-study liver biopsy.
UNASSIGNED: Efruxifermin was safe and well-tolerated; most adverse events (AEs) were grade 1 (n = 7, 23.3%) or grade 2 (n = 19, 63.3%). The most frequent AEs were gastrointestinal, including transient, mild to moderate diarrhea, and/or nausea. Significant improvements were noted in key markers of liver injury (alanine aminotransferase) and glucose and lipid metabolism. Sixteen-week treatment with efruxifermin was associated with significant reductions in non-invasive markers of fibrosis including Pro-C3 (least squares mean change from baseline [LSMCFB] -9 μg/L efruxifermin vs. -3.4 μg/L placebo; p = 0.0130) and ELF score (-0.4 efruxifermin vs. +0.4 placebo; p = 0.0036), with a trend towards reduced liver stiffness (LSMCFB -5.7 kPa efruxifermin vs. -1.1 kPa placebo; n.s.). Of 12 efruxifermin-treated patients with liver biopsy after 16 weeks, 4 (33%) achieved fibrosis improvement of at least one stage without worsening of NASH, while an additional 3 (25%) achieved resolution of NASH, compared to 0 of 5 placebo-treated patients.
UNASSIGNED: Efruxifermin appeared safe and well-tolerated with encouraging improvements in markers of liver injury, fibrosis, and glucose and lipid metabolism following 16 weeks of treatment, warranting confirmation in larger and longer term studies.
UNASSIGNED: Cirrhosis resulting from non-alcoholic steatohepatitis (NASH), the progressive form of non-alcoholic fatty liver disease, represents a major unmet medical need. Currently there are no approved drugs for the treatment of NASH. This proof-of-concept randomized, double-blind clinical trial demonstrated the potential therapeutic benefit of efruxifermin treatment compared to placebo in patients with cirrhosis due to NASH.
UNASSIGNED: NCT03976401.