想问问StephenW

sunpk861007

通过与杰华生物公司何先生联系，了解到乐复能治疗乙肝临床试验是二期与三期同时进行，二期在北京佑安医院，三期在湖南几家医院，目前正在做总结报告，据其说，治疗乙肝效果蛮好，但是上报药监局并审批过程存在不确定性，希望能得到上市许可。
个人感觉1.乐复能治疗乙肝临床试验医院较少，相比较国内乙克，合成肽大规模的临床试验来说，乐复能试验有点不是那么有说服力，2.临床试验未用空白对照，不知是否符合要求.3.用普通干扰素治疗三个月，并未达到干扰素要求疗程的.4.对其能否审批成功很担心 以上其他战友可否讨论下

怕脂肪肝

乙克

StephenW

回复 sunpk861007 的帖子

GS 9260是TLR7的激动剂(agonist)。它会绑定(bind)到免疫细胞表面TLR7受体, 导致细胞因子(cytokines)的生产，包括干扰素。是一种口服药物。据报道，是安全的。
大家都在猜测，Gilead公司可能会进行进一步的临床试验.

GS 9260 is a TLR7 agonist. That is,  it will bind to Toll Like, TL7 receptors on the surface of immune cells leading to the production of cytokines, including Interferon. It is an oral drug. It has been reported to be safe in human.
We are guessing Gilead may be conducting further clinical trials.

GS-9620 in Humans
                  
Finally, U. Lopatin and colleagues tested the safety, pharmacokinetics,  and pharmacodynamics of GS-9620 in human volunteers without  viral hepatitis.
                  
This double-blind placebo-controlled study included 75 healthy volunteers. A majority were men and white, and the average age was about 30 years. Participants received single ascending doses of 0.3, 1, 2, 4, 6, 8, and 12 mg GS-9620; 7 cohorts took the                   drug on an empty stomach and 3 cohorts took it with food.
                  
GS-9620 was generally safe and well tolerated with single doses  through 12 mg. The most common adverse events were headaches, chills, and fever. There were no serious adverse events or discontinuations due to adverse events or laboratory abnormalities. A total of        49 treatment-emergent events in 15 people were judged to be drug-related. The number of adverse events increased with higher doses, from 1 per cohort with 2, 4, or 6 mg, to 11 with 8 mg and 31 with 12 mg. Some participants experienced mild platelet decreases, but these changes were "not notable enough to  be considered adverse events," according to the researchers.
                  
GS-9620 treatment led to dose-dependent increases in various  cytokines, chemokines, and interferon-stimulated genes. Systemic interferon changes were only seen with the 12mg dose. Volunteers receiving the 8 mg and 12 mg doses experienced increases in        percentages of activated T-cells, B-cells, and NK cells. "GS-9620 is a potent, oral small molecule agonist of TLR7, which was  safe and well tolerated in single ascending doses up to 12 mg by mouth," the investigators concluded.
"These findings confirm the preclinical data suggesting that GS-9620 induces multiple cytokines (including Interferon) pre-systemically, with the potential for decreased adverse events compared to  systemic pegylated interferon," they continued. "GS-9620 is a promising, oral immunomodulatory agent with potency in the low milligram range and a therapeutic window which supports  further evaluation in the therapy of viral hepatitis B and C."

interdetect

回复 StephenW 的帖子

临床测试中，创新药物“乐复能”，阳性对照药物为治疗慢性乙型肝炎常用药物——干扰素α—2b，二者以1：1的比例分为A、B两组进行编盲，采用国际通行的随机双盲方法开展临床研究，共入组慢性乙型肝炎病人360例，研究治疗期为3个月，疗后随访期为6个月，一共进行为期为9个月的临床研究和观察。所有研究病例的筛查和剔除，主要指标的第三方复查以及数据最终确认等均在盲态下进行。经专家审核，共计352例纳入全分析集（FAS），294例纳入符合方案集（PPS）。数据管理和统计符合国家药监局《药品临床实验管理规范》的相关要求。
　　
　　而从现场揭盲结果显示，以国际公认的乙肝治疗满意疗效指标——e抗原转阴率为例：对照药物组使用干扰素α-2b治疗e抗原转阴率在3个月治疗结束时为25.00%，疗后3个月和6个月随访分别为24.55%和21.88%；研究药物组使用创新药乐复能治疗，e抗原转阴率在3个月治疗结束时为33.89%，；疗后3个月和6个月随访分别为42.35%和51.11%！据文献资料显示，目前临床常用治疗慢性乙型肝炎的药物，包括美国FDA批准的长效干扰素在内的干扰素类和核苷（酸）类药物，对慢性乙型肝炎病人经过9—12个月的系统治疗，e抗原转阴率也只在20—30%左右。

interdetect

回复 灰天 的帖子

目前仅处于临床试验阶段，公布数据也不明确，所以不能下结论。
评价一个药物治疗乙肝最基本应阐述一下指标：
1、抑制HBV DNA的能力
2、ALT复常率
3、HBeAg血清学转换率
除此之外，如果有HBsAg转阴/血清学转换率将是最理想的。
单纯的谈HBeAg的转阴率，没太大意思。

把握当下

StephenW 发表于 2012-2-11 14:35
回复 sunpk861007 的帖子

GS 9260是TLR7的激动剂(agonist)。它会绑定(bind)到免疫细胞表面TLR7受体, 导致 ...

可否理解为一种口服干扰素？有意思，希望它的副作用也能大大减少：）

StephenW

回复 把握当下 的帖子

可否理解为一种口服干扰素？有意思，希望它的副作用也能大大减少：）

jixuxiangqian

在SCI检索Novaferon居然没有一篇文献？？？为什么？