Replicor宣布招聘的IIb期临床试验REP 2139 - 镁或REP 2165 - 镁联合V

StephenW

Media Contact:
Alexandra Peterson

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212-508-9709

                                                                                                                 

[p=25, null, left]Replicor announces initiation of recruitment for its Phase IIb clinical trial with REP 2139-Mg or REP 2165-Mg in combination with Viread® and Pegasys® or Zadaxin® in patients with HBeAg negative chronic hepatitis B infection

[p=25, null, left]New York – October 4, 2015 – Replicor announces that the recruitment of patients is underway for its second Phase II trial in Caucasian patients that will assess the safety and antiviral efficacy of REP 2139-Mg or REP 2165-Mg in combination with Viread® and Pegasys® or Zadaxin® in patients with HBeAg negative chronic hepatitis B infection.

[p=25, null, left]The design of the REP 401 protocol (NCT02565719) draws on Replicor’s experience with REP 2055 and REP 2139-Ca from its 4 previous Phase II trials in Asian and Caucasian patients with HBV or HBV / HDV infection. This randomized controlled trial will introduce the next generation formulation of REP 2139 (REP 2139-Mg) and a new NAP, REP 2165 (as REP 2165-Mg).  REP 2165 is a version of REP 2139 designed to be more rapidly eliminated from the body which in pre-clinical evaluations showed similar antiviral activity with significantly reduced accumulation in the liver compared to REP 2139.

[p=25, null, left]The EU GCP compliant REP 401 protocol is being conducted in Moldova and will consist of 60 Caucasian patients with HBeAg negative chronic HBV infection, all of whom will receive 24 weeks of Viread® exposure before entering the combination phase of therapy.  30 of these patients (while continuing Viread® therapy) will be randomized into three experimental arms:

REP 2139-Mg + Pegasys® for 48 weeks

REP 2139-Mg + Zadaxin® for 48 weeks

REP 2165-Mg + Pegasys® for 48 weeks.

[p=25, null, left]The other 30 patients will be randomized into comparator control arms receiving either Pegasys® or Zadaxin® (in the absence of NAP therapy) in addition to continuing Viread®.  All patients in the comparator control arms demonstrating futility of therapy (as defined by < 3 log reduction in serum HBsAg from baseline after receiving 24 weeks combination therapy) will be eligible for randomized crossover to an experimental arm to receive 48 weeks of NAP therapy while continuing their current combination therapy.   Follow up assessment after halting all treatment is planned for 48 weeks.

[p=25, null, left]For more information please visit the clinicaltrials.org website:

https://clinicaltrials.gov/ct2/show/NCT02565719?term=2139&rank=1

StephenW

媒体联系：
亚历山德拉·彼得森

[email protected]

212-508-9709

                                                                                                                 

Replicor宣布招聘的IIb期临床试验REP 2139 - 镁或REP 2165 - 镁联合Viread®和Pegasys®或Zadaxin®患者HBeAg阴性慢性乙型肝炎病毒感染的开始

纽约 - 2015年10月4日 - Replicor宣布，患者招募正在进行的第二阶段II试验的白人患者，将评估REP 2139 - 镁或REP 2165-Mg系的安全性和抗病毒疗效，结合Viread®和Pegasys®或Zadaxin®患者HBeAg阴性慢性乙型肝炎病毒感染。

在REP 401协议的设计（NCT02565719）借鉴了Replicor的经验REP 2055和REP 2139钙从它在亚洲和高加索例HBV或HBV / HDV感染4以前的II期临床试验。这种随机对照试验将推出REP 2139（REP 2139 - 镁）和一个新的国家行动方案，REP 2165（如REP 2165-Mg）的下一代配方。 REP 2165是版本REP 2139的设计是更快速地从体内排出这在临床前评价显示与在肝中显著减少积累相比REP 2139类似的抗病毒活性。

欧盟GCP标准REP 401协议在摩尔多瓦正在进行和将包括60白人患者HBeAg阴性慢性HBV感染者，他们都将获得Viread®曝光24周进入治疗相结合阶段之前。 30这些患者（同时继续Viread®疗法）将被随机分成三个实验武器：

REP 2139镁+Pegasys®48周

REP 2139镁+Zadaxin®48周

REP 2165镁+Pegasys®48周。

除了继续Viread®另外30名患者将被随机分为接受任何Pegasys®或Zadaxin®（在没有国家行动方案治疗）比较控制臂。在比较控制臂证明的治疗无益（如接收24周联合治疗后，确定由基线血清HBsAg <3数减少）所有患者均可获得随机交叉到实验组接受48周NAP治疗的同时继续其当前联合治疗。暂停计划48周，所有治疗后随访评估。

欲了解更多信息，请访问c​​linicaltrials.org网站：

https://clinicaltrials.gov/ct2/s ... erm=2139&rank=1

StephenW

https://clinicaltrials.gov/ct2/show/NCT02565719?term=2139&rank=1

Purpose

NAPs have been previously shown to clear serum hepatitis B virus surface antigen (HBsAg) both preclinically (in duck HBV infected ducks) and in human patients. REP 2139-Ca mediated HBsAg clearance acts synergistically with immunotherapeutic agents such as pegylated interferon-alpha 2a and thymosin alpha-1 to restore host immunological control of HBV infection. REP 2165 is a version of REP 2139 which has been shown preclinically to retain antiviral activity with lower accumulation in the liver.

Both REP 2139 and REP 2165 used in this protocol are formulated as magnesium chelate complexes, which improve their administration tolerability. This study will examine the safety and efficacy of REP 2139-Mg and REP 2165-Mg therapy in patients with HBeAg negative chronic hepatitis B when used in combination with tenofovir disoproxil fumarate and pegylated interferon alpha-2a or thymosin alpha-1.

Estimated Enrollment:         60
Study Start Date:         September 2015
Estimated Study Completion Date:         December 2018
Estimated Primary Completion Date:         April 2018 (Final data collection date for primary outcome measure)

Detailed Description:

Nucleic acid polymers (NAPs) utilize the sequence independent properties of phosphorothioated oligonucleotides to target apolipoprotein interactions involved in the formation of HBV subviral particles (SVPs) which are comprised mainly of the hepatitis B surface antigen protein (HBsAg). The effect of NAPs is to block the formation of SVPs inside infected hepatocytes which prevents their secretion. As SVPs account for > 99.99% of HBsAg in the blood, NAPs are an effective approach for clearing HBsAg from the serum of HBV infected patient.

Previous clinical trials have demonstrated that treatment with the NAP REP 2139 (REP 2139-Ca) results in the rapid and effective clearance ofHBsAg from the blood. This HBsAg removal has the immediate effect of unmasking the underlying, pre-existing anti-HBsAg (anti-HBs) response, allowing clearance of HBV virus from the blood.

Although REP 2139-Ca has been shown to be safe in human patients, it shares the same class effect as other phosphorothioate oligonucleotides in that it accumulates in the liver with repeated dosing. REP 2165 is a version of REP 2139 which is designed to have an increased rate of degradation to slow down liver accumulation while keeping its antiviral activity intact. The antiviral efficacy of REP 2165 has been shown to be comparable to REP 2139 in a pre-clinical model of HBV infection with significantly less accumulation in the liver. As such, REP 2165 is expected to have comparable antiviral efficacy in human patients with reduced liver accumulation during treatment.

HBsAg has important immunosuppressive effects in HBV infection which have been shown to block both adaptive and innate immune processes. Removal of HBsAg from the blood of patients removes this immunosuppressive effect.

Thus, an important additional effect of removal of HBsAg from the blood is to greatly enhance the effect of immunotherapeutic agents like pegylated interferon alpha 2a and thymosin alpha 1. It is expected that elimination of serum HBsAg with REP 2139-Mg or REP 2165-Mg will lead to creation of a favourable immunological activation in the absence of HBsAg, appearance of free anti-HBs, clearance of HBV virions in the blood and synergistic immunostimulation with conventional dosing of Pegasys® or Zadaxin® and improved control of HBV infection in the presence of Viread®.

StephenW

用途

行动方案先前已显示以清除血清乙肝病毒表面抗原（HBsAg）既临床前（在鸭乙型肝炎病毒感染鸭），并在人类患者。 REP 2139钙介导的HBsAg清除协同作用与免疫治疗剂，如聚乙二醇化干扰素α2a和胸腺素α-1，恢复HBV感染的宿主免疫控制。 REP 2165是版本REP 2139的已显示临床前保持抗病毒活性与在肝中积累降低。

无论REP 2139和REP 2165在这个协议中使用配制成镁螯合物，从而提高他们的管理耐受性。这项研究将考察REP 2139-Mg和REP 2165镁治疗的患者HBeAg阴性慢性乙型肝炎的安全性和有效性结合使用富马酸替诺福韦酯和聚乙二醇干扰素α-2a或胸腺素α-1时。

预计招生：60
研究开始日期：2015年九月
研究预计竣工日期：2018年十二月
预计初步竣工日期：2018年4月（为主要成果的措施的最终数据采集日期）

详细说明：

核酸聚合物（行动方案）利用硫化磷酸酯寡核苷酸的序列独立属性来靶向涉及乙肝病毒亚病毒颗粒（的SVP），其主要包括乙肝表面抗原蛋白（HBsAg的）的形成载脂蛋白相互作用。的行动方案的效果是阻止形成SVP的内感染的肝细胞从而防止其分泌。至于的SVP占乙肝表面抗原在血液> 99.99％，国家行动方案是一个有效的方法从乙肝病毒感染的病人的血清中乙肝表面抗原清除。

先前的临床试验已经证明与NAP的REP 2139（REP 2139-Ca）的结果中，从血液中的快速和有效地清除ofHBsAg治疗。这乙肝表面抗原清除有揭露潜在的，预先存在的抗乙肝表面抗原（抗-HBs）反应，使乙肝病毒的清除从血液中的立竿见影的效果。

虽然REP 2139钙已被证明是安全的人类患者，它共享相同的类的效果，因为它堆积在与重复给药肝脏其他硫代磷酸酯寡核苷酸。 REP 2165是版本REP 2139的，其目的是有退化的增加的速率减慢肝积累，同时保持其抗病毒活性不变。 REP 2165的抗病毒效力已被证明可媲美REP 2139在HBV感染的临床前模型中的肝脏显著更少的积累。这样，REP 2165预期在人类患者的降低肝积累可比抗病毒效力治疗期间。

的HBsAg在HBV感染的重要的免疫抑制作用已显示阻断两者适应性和先天免疫过程。从患者血液中清除乙肝表面抗原消除这种免疫抑制作用。

因此，去除的HBsAg的从血液一个重要的额外效果是大大提高免疫治疗剂像聚乙二醇化的干扰素α2a和胸腺素α1的效果预计消除血清HBsAg与REP 2139 - 镁或REP 2165 - 镁会导致创作在没有乙肝表面抗原，外观无​​抗-HBs，乙肝病毒粒子在血液中的清除和协同免疫刺激与Pegasys®或Zadaxin®常规剂量和HBV感染的改进的控制中存在一个有利的免疫激活的Viread®。

zgct

谢谢

hao2014

好的，继续折腾3年，这公司

你就拖吧

当心市场没了，到时候哭吧

重韧

从这么早出来。到现在2B到18年。也是醉了。。还没有融到钱，还是圈到钱在这里拖时间。。