A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis.
A randomized, placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis.
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DOI：
10.1002/hep.29477
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Lefebvre E
中科院分区：
文献类型：
--
作者：
Friedman SL;Ratziu V;Harrison SA;Abdelmalek MF;Aithal GP;Caballeria J;Francque S;Farrell G;Kowdley KV;Craxi A;Simon K;Fischer L;Melchor-Khan L;Vest J;Wiens BL;Vig P;Seyedkazemi S;Goodman Z;Wong VW;Loomba R;Tacke F;Sanyal A;Lefebvre E
本研究的目的是评估赛尼克韦罗（CVC），C-C趋化因子受体2型和5型的双重拮抗剂，用于治疗非酒精性脂肪性肝炎（NASH）伴肝纤维化（LF）。一项随机、双盲、多国、IIb期研究在81家临床研究中心招募了NASH、非酒精性脂肪肝疾病活动性评分（NAS）≥4和LF（1 - 3期，NASH临床研究网络）受试者。受试者（N = 289）被随机分配CVC 150 mg或安慰剂。主要结局为第1年NAS改善≥2分且纤维化未恶化。关键次要结局为：脂肪性肝炎（SH）消退且纤维化未恶化;纤维化改善≥1期且SH未恶化。评估炎症和不良事件的生物标志物。完成了全部研究招募。在接受CVC（N = 145）和安慰剂的受试者中，达到意向治疗人群中NAS改善和SH消退的主要终点的比例相似（N = 144;分别为16% vs. 19%，P = 0.52和8% vs. 6%，P = 0.49）。然而，与安慰剂相比，在接受CVC的显著更多的受试者中达到纤维化终点（20%对10%; P = 0.02）。基线时疾病活动度和纤维化分期较高的患者治疗获益更大。全身性炎症的生物标志物用CVC减少。CVC的安全性和耐受性与安慰剂相当。结论：在CVC治疗1年后，与安慰剂相比，两倍多的受试者实现了纤维化的改善并且SH没有恶化。鉴于迫切需要在NASH中开发抗纤维化疗法，这些发现值得进行3期评价。（Hepatology 2018;67：1754 - 1767）。
The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of C—C chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis (LF). A randomized, double‐blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score (NAS) ≥4, and LF (stages 1‐3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2‐point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis (SH) and no worsening of fibrosis; improvement in fibrosis by ≥1 stage and no worsening of SH. Biomarkers of inflammation and adverse events were assessed. Full study recruitment was achieved. The primary endpoint of NAS improvement in the intent‐to‐treat population and resolution of SH was achieved in a similar proportion of subjects on CVC (N = 145) and placebo (N = 144; 16% vs. 19%, P = 0.52 and 8% vs. 6%, P = 0.49, respectively). However, the fibrosis endpoint was met in significantly more subjects on CVC than placebo (20% vs. 10%; P = 0.02). Treatment benefits were greater in those with higher disease activity and fibrosis stage at baseline. Biomarkers of systemic inflammation were reduced with CVC. Safety and tolerability of CVC were comparable to placebo. Conclusion: After 1 year of CVC treatment, twice as many subjects achieved improvement in fibrosis and no worsening of SH compared with placebo. Given the urgent need to develop antifibrotic therapies in NASH, these findings warrant phase 3 evaluation. (Hepatology 2018;67:1754‐1767).
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DOI：
10.1056/nejmoa0907929
发表时间：
2010-05-06
期刊：
The New England journal of medicine
影响因子：
--
作者：
Sanyal AJ;Chalasani N;Kowdley KV;McCullough A;Diehl AM;Bass NM;Neuschwander-Tetri BA;Lavine JE;Tonascia J;Unalp A;Van Natta M;Clark J;Brunt EM;Kleiner DE;Hoofnagle JH;Robuck PR;NASH CRN
通讯作者：
NASH CRN
DOI：
10.1111/cts.12397
发表时间：
2016-06
期刊：
Clinical and translational science
影响因子：
--
作者：
Lefebvre E;Gottwald M;Lasseter K;Chang W;Willett M;Smith PF;Somasunderam A;Utay NS
通讯作者：
Utay NS
影响因子：
29.4
作者：
Angulo P;Kleiner DE;Dam-Larsen S;Adams LA;Bjornsson ES;Charatcharoenwitthaya P;Mills PR;Keach JC;Lafferty HD;Stahler A;Haflidadottir S;Bendtsen F
通讯作者：
Bendtsen F
影响因子：
2.2
作者：
Friedman, Scott;Sanyal, Arun;Ratziu, Vlad
通讯作者：
Ratziu, Vlad
DOI：
10.1097/qai.0b013e318213c2c0
发表时间：
2011-06-01
影响因子：
3.6
作者：
Lalezari, Jacob;Gathe, Joseph;Palleja, Sandra M.
通讯作者：
Palleja, Sandra M.