gs9620 两个双盲，1B阶段结果

newchinabok

http://www.ncbi.nlm.nih.gov/pubmed/25733157#

newchinabok

J Hepatol. 2015 Feb 27. pii: S0168-8278(15)00147-6. doi: 10.1016/j.jhep.2015.02.037. [Epub ahead of print]
The Oral Toll-Like Receptor-7 Agonist GS-9620 in Patients with Chronic Hepatitis B Virus Infection.
Gane EJ1, Lim YS2, Gordon SC3, Visvanathan K4, Sicard E5, Fedorak RN6, Roberts S7, Massetto B8, Ye Z8, Pflanz S8, Garrison KL8, Gaggar A8, Mani Subramanian G8, McHutchison JG8, Kottilil S9, Freilich B10, Coffin CS11, Cheng W12, Kim YJ13.
Author information
Abstract
BACKGROUND:
GS-9620 is an oral agonist of toll-like receptor 7, a pattern-recognition receptor whose activation results in innate and adaptive immune stimulation. We evaluated the safety, pharmacokinetics, and pharmacodynamics of GS-9620 in patients with chronic hepatitis B.
METHODS:
In two double-blind, phase 1b trials of identical design, 49 treatment-naïve and 51 virologically suppressed patients were randomized 5:1 to receive GS-9620 (at doses of 0.3 mg, 1 mg, 2 mg, 4 mg) or placebo as a single dose or as two doses 7 days apart. Pharmacodynamic assessment included evaluation of peripheral mRNA expression of interferon-stimulated gene 15 (ISG15), serum interferon gamma-induced protein 10 and serum interferon (IFN)-alpha.
RESULTS:
Overall, 74% of patients were male and 75% were HBeAg negative at Baseline. No subject discontinued treatment due to adverse events. Fifty-eight percent experienced ⩾1 adverse event, all of which were mild to moderate in severity. Overall, the most common adverse event was headache. No clinically significant changes in HBsAg or HBV DNA levels were observed. Overall, a transient dose-dependent induction of peripheral ISG15 gene expression was observed peaking within 48 hours of dosing followed by return to baseline levels within 7 days. Higher GS-9620 dose, HBeAg positive status, and low HBsAg level at baseline were independently associated with greater probability of ISG15 response. Most patients (88%) did not show detectable levels of serum IFN-alpha at any time point.
CONCLUSIONS:
Oral GS-9620 was safe, well tolerated, and associated with induction of peripheral ISG15 production in the absence of significant systemic IFN-alpha levels or related symptoms.
Copyright © 2015. Published by Elsevier B.V.
KEYWORDS:
HBsAg; Hepatitis B virus; Immune response; TLR

PMID: 25733157 [PubMed - as supplied by publisher]

newchinabok

肝脏病学杂志。 2015年2月27日


口腔Toll样受体激动剂7 GS-9620治疗慢性乙型肝炎病毒感染。
甘恩EJ1，林YS2，戈登SC3，Visvanathan K4，SICARD E5，Fedorak RN6，罗伯茨S7，马赛托B8，叶Z8，Pflanz S8，驻军KL8，Gaggar A8，玛尼萨勃拉曼尼亚G8，McHutchison JG8，Kottilil S9，Freilich B10，棺材CS11，郑W12，金YJ13。
作者信息
抽象
背景：
GS-9620是toll样受体7，模式识别受体的活化导致先天和适应性免疫刺激的口服激动剂。我们评估了安全，药代动力学和GS-9620的药效学与慢性乙型肝炎
方法：
在2双盲，相位相同设计1b的试验中，49初治和51病毒学抑制患者被随机5:1至接收GS-9620（剂量为0.3毫克，1毫克，2毫克，4毫克）或安慰剂作为单剂量或作为两剂间隔7天。药效学评价包括干扰素刺激基因15（ISG15），血清干扰素γ诱导的蛋白10和血清干扰素（IFN）-α外周血mRNA表达的评价。
结果：
总体而言，74％的病人为男性，75％为HBeAg阴性的基线。无主题停止治疗，由于不良事件。百分之五十八经历⩾1不良事件，所有这一切都为轻度至中度。总体而言，最常见的不良事件是头痛。在乙肝表面抗原或HBV DNA水平没有临床显著的变化进行观察。总体而言，一过性的剂量依赖性诱导外周血ISG15基因表达的观察48小时给药的随后7天内恢复到基线水平内的尖峰。较高的GS-9620的剂量，HBeAg阳性的状态和低的HBsAg水平基线独立与ISG15响应概率较大有关。大多数患者（88％），在任何时间点没有显示出血清的IFN-α的检测水平。
结论：
口服的GS-9620是安全的，耐受性良好，并且与感应外围ISG15生产在没有显著全身的IFN-α水平或相关的症状相关联。
版权所有©2015年出版由Elsevier B.V.
关键词：
乙肝表面抗原; B型肝炎病毒;免疫反应; TLR

结论：25733157 [考研 - 由出版商提供]

newchinabok

Overall, the most common adverse event was headache. No clinically significant changes in HBsAg or HBV DNA levels were observed.
总体而言，最常见的不良事件是头痛。在乙肝表面抗原或HBV DNA水平没有临床显著的变化进行观察。

newchinabok

好像没效

阳光醉人

1B是不是只测试安全性，意思是说没进行DNA对比。

rikk

看起来没效果

newchinabok

回复 阳光醉人 的帖子

安全，药代动力学和GS-9620的药效学

重韧

没有提到病毒这块的反馈。只提到身体反应，是不是还没有到那一步，这种测试还要用“盲”吗？如果只是安全测试的话。

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回复 重韧 的帖子

https://www.clinicaltrials.gov/c ... 0&Search=Search