肝胆相照论坛

标题: Replicor新APASL 2019年HBV高功能治愈率的分析 [打印本页]

作者: StephenW 时间: 2019-2-12 09:57 标题: Replicor新APASL 2019年HBV高功能治愈率的分析

Replicor to update analysis of high rates of functional cure of HBV at APASL 2019

MONTREAL, February 11, 2019 – Replicor Inc., a privately held biopharmaceutical company targeting a cure for chronic hepatitis B and D patients, today announced it will present analysis of its HBV functional cure data from the ongoing REP 401 study at the 2019 meeting of the Asian Pacific Association for the Study of the Liver (APASL) to be held February 20-24, 2019 in Manila, Philippines.

The REP 401 protocol (NCT02565719) is a randomized, controlled trial assessing the safety and efficacy of REP 2139-Mg and REP 2165-Mg when used in combination with tenofovir disoproxil fumarate (TDF) and pegylated interferon alpha 2a (peg-IFN) in patients with chronic HBeAg negative HBV infection.

Replicor’s plenary oral presentation will occur during the Autoimmune and Viral Hepatitis Symposium on February 23, 2019 and will include updated mechanistic data as well as the current follow-up analysis after removal of all treatment demonstrating further treatment is no longer required in 85% of patients completing therapy.

Replicor’s presentation from APASL 2019 will be available on the company’s website following their disclosure at the meeting at www.replicor.com/science/conference-presentations. For further information about the 2019 APASL Meeting visit: https://apasl2019manila.org/.

作者: StephenW 时间: 2019-2-12 09:57

复制器更新APASL 2019年HBV高功能治愈率的分析

蒙特利尔，2019年2月11日 - Replicor Inc.是一家私人控股的生物制药公司，目标是治疗慢性乙型和乙型肝炎患者，今天宣布将在2019年的会议上对正在进行的REP 401研究中的HBV功能治愈数据进行分析。亚太肝脏研究协会（APASL）将于2019年2月20日至24日在菲律宾马尼拉举行。

REP 401方案（NCT02565719）是一项随机对照试验，评估REP 2139-Mg和REP 2165-Mg与替诺福韦地索普西富马酸盐（TDF）和聚乙二醇化干扰素α2a（peg-IFN）联合使用时的安全性和有效性。慢性HBeAg阴性HBV感染的患者。

Replicor的全体口头报告将在2019年2月23日的自身免疫和病毒性肝炎研讨会期间进行，并将包括更新的机械数据以及去除所有治疗后的当前随访分析，证明85％的患者不再需要进一步治疗完成治疗。

复制者2019年APASL的演示文稿将在公司网站上公布后在www.replicor.com/science/conference-presentations上公布。有关2019年APASL会议的更多信息，请访问：https：//apasl2019manila.org/。

作者: 齐欢畅 时间: 2019-2-12 21:42

作者: 齐欢畅 时间: 2019-2-12 21:42

Replicor’s plenary oral presentation will occur during the Autoimmune and Viral Hepatitis Symposium on February 23, 2019 and will include updated mechanistic data as well as the current follow-up analysis after removal of all treatment demonstrating further treatment is no longer required in 85% of patients completing therapy.

作者: pourvivre 时间: 2019-2-13 09:36

good news.

作者: 灵魂不屈 时间: 2019-2-13 11:49

请问85%的患者不再需要进一步治疗，这是什么意思？表抗转阴了？

作者: pourvivre 时间: 2019-2-13 11:51

本帖最后由 pourvivre 于 2019-2-12 23:00 编辑

回复灵魂不屈的帖子

达不到指南要求的治疗标准

作者: 左罗 时间: 2019-2-13 11:58

这应该是近半月以来最值得关注的好消息了！

作者: 齐欢畅 时间: 2019-2-13 12:01

左罗发表于 2019-2-13 11:58
这应该是近半月以来最值得关注的好消息了！

作者: 齐欢畅 时间: 2019-2-13 12:05

我觉得这个结果还是很不错的，看到rep公司的股票也是涨了很多，当然具体结果还不算特别好，至少未百分之百。
但联合用药，只是用了基本的几种，就有如此结果。算不错了。罗马不是一天建成的。
接下来还是关注，至少说明这个路子是可行的。

作者: newchinabok 时间: 2019-2-13 12:08

本帖最后由 newchinabok 于 2019-2-13 12:10 编辑

REP 2139-ca怎么样了，以前治愈hbv很牛逼，现在换成REP 2139-Mg和REP 2165-Mg

作者: pourvivre 时间: 2019-2-13 12:12

本帖最后由 pourvivre 于 2019-2-12 23:18 编辑

回复齐欢畅的帖子

HBSAG ANTI-HBS 在停药后有些反弹，但是HBV-DNA在停药后继续降低，ALT在停药后复常率高，肝弹值停药后降低。说明思路比较正确，REP降表抗，TDF降病毒，干扰素激发T,B细胞，直接作用ccc-DNA，逆转病情发展趋势。需要治愈，还要继续研究剂量，疗程等需要继续等待更多用作统计的数据。相信效果会提升。乙肝难治，问题在于免疫功能被抗原和病毒拟制，去除干扰，同时用干扰素等激发免疫，弹药才能送到病毒老巢。（治疗期间ALT升高）

作者: 齐欢畅 时间: 2019-2-13 12:18

pourvivre 发表于 2019-2-13 12:12
回复齐欢畅的帖子

HBSAG ANTI-HBS 在停药后有些反弹，但是HBV-DNA在停药后继续降低，ALT在停药后复常率 ...

不错不错。大家看看新研发的药物库中，有没有可以协同治疗的药物，来个三联用，四联用

作者: StephenW 时间: 2019-2-13 13:09

齐欢畅发表于 2019-2-13 12:05
我觉得这个结果还是很不错的，看到rep公司的股票也是涨了很多，当然具体结果还不算特别好，至少未百分之百 ...

据我所知，Replicor是一家私营公司，其股票不在市场上交易.

作者: StephenW 时间: 2019-2-13 13:15

pourvivre 发表于 2019-2-13 12:12
回复齐欢畅的帖子

HBSAG ANTI-HBS 在停药后有些反弹，但是HBV-DNA在停药后继续降低，ALT在停药后复常率 ...

如果HBsAg转为阴性，HBsAb阳性在停药后据报道没有反弹.

作者: cgg 时间: 2019-2-13 15:03

本帖最后由 cgg 于 2019-2-13 15:06 编辑

下面我是从官网查到的信息。这个药物已经研发了超过10年了，现在采取了联合治疗的手段，有40%的概率能达到产生抗体了，很不错了，如果再加上一个免疫调节剂（市场上可能没有好的产品），说不定治愈率能达到80%以上，如果那样就好了。

作者: 左罗 时间: 2019-2-13 15:13

尤其关注3个重要节点：
●亚太肝脏研究协会（APASL）将于2019年2月20日至24日在菲律宾马尼拉举行。
●慢性HBeAg阴性HBV感染的患者。
●证明85％的患者不再需要进一步治疗以完成治疗。

作者: ivanich 时间: 2019-2-13 15:46

这个东东神不知鬼不觉的进展啊！真是个好消息，有木有大神普及一下这个药物的机理？我想如果不出意外这个药和箭头的那个，基本可以干掉hbv了，当然要完全清除cccDNA可能还不行！

作者: fuke 时间: 2019-2-13 16:01

回复 ivanich 的帖子

这个药物已经出来很多年了，一直都是实验效果非常好。但是一直没有推进到三期，二期已经做了快十年了。不知道这次会不会推进到三期。

作者: hao2014 时间: 2019-2-13 16:38

回复齐欢畅的帖子

Rep的股票？？哪个？？

作者: hao2014 时间: 2019-2-13 16:42

我很想知道的是

这个药（也许经过修正了）为什么临床要做这么久？？七八年前就是类似的好消息了

到底是不是之前的版本有问题？？现在最新版本修正了哪些问题？？

拭目以待

看到底是十年磨一剑还是十年大忽悠

作者: newchinabok 时间: 2019-2-13 17:51

本帖最后由 newchinabok 于 2019-2-13 17:52 编辑

hao2014 发表于 2019-2-13 16:42
我很想知道的是

这个药（也许经过修正了）为什么临床要做这么久？？七八年前就是类似的好消息了

rep9ac治乙肝很牛逼，变成rep2139，后来治乙肝很牛逼，又变成rep2139ca，很牛逼，又变成rep2139mg和REP 2165-Mg

作者: fuke 时间: 2019-2-13 18:01

就是打死也不进三期

作者: 齐欢畅 时间: 2019-2-13 18:55

哦我说错了，不是股票

作者: hao2014 时间: 2019-2-13 19:06

回复 newchinabok 的帖子

总而言之

就是越来越牛逼

酒越陈越香

这好药啊，再等个十来年，越来越好

作者: mingbai 时间: 2019-2-13 19:28

看了第一页，满满的希望，看到最后一页，又失望了。最靠谱的还是衣壳抑制剂吧？

作者: newchinabok 时间: 2019-2-13 20:22

本帖最后由 newchinabok 于 2019-2-13 20:23 编辑

mingbai 发表于 2019-2-13 19:28
看了第一页，满满的希望，看到最后一页，又失望了。最靠谱的还是衣壳抑制剂吧？ ...

你都是论坛中将军长级别了，不该看见新闻就激动的层次吧

作者: mingbai 时间: 2019-2-13 22:44

newchinabok 发表于 2019-2-13 20:22
你都是论坛中将军长级别了，不该看见新闻就激动的层次吧

谁叫发帖的是大神呢。

作者: pourvivre 时间: 2019-2-14 08:29

本帖最后由 pourvivre 于 2019-2-13 19:33 编辑

我的主治医生曾跟我说现在有很好的试验结果，但不建议我去做实验，说可能将来我可能享受到这些试验结果，所以不知道他谈论的是不是这个REP药物。这个公司应该和我看病随访的医院有合作关系。而且这个公司从我工作的地方可以步行到达。这是我对这个公司感兴趣的原因之一，因为同城。去年曾关注过他们在Moldova 做E抗原阴性患者试验的结果，我更想知道他们长期停药后的治疗结果。

作者: fuke 时间: 2019-2-14 09:15

回复 pourvivre 的帖子

这家公司说加拿大的吧

作者: pourvivre 时间: 2019-2-14 10:51

回复 fuke 的帖子

是的

作者: fuke 时间: 2019-2-14 10:55

回复 pourvivre 的帖子

有空给我们拍拍这个公司的照片，规模怎么样。让大家了解了解这个公司啊

作者: pourvivre 时间: 2019-2-14 11:15

本帖最后由 pourvivre 于 2019-2-13 22:18 编辑

回复 fuke 的帖子

一个附近工业园的普通小公司

作者: StephenW 时间: 2019-2-14 12:10

回复 mingbai 的帖子

不要失望. 论坛中有很多偏见. 由于Replicor的临床试验，现在已经认识到降低血清HBsAg是功能性治愈的第一步 (RNAi就是一个例子).

我对这家公司仍然充满希望.

作者: 左罗 时间: 2019-2-14 12:30

回复 StephenW 的帖子

你是这个领域里难得的大咖级人士，我们真诚的尊敬、感激、谢谢你义务为大家经常提供的最新信息，以及一些积极客观的观点、评论和看法。再次道一声谢谢！辛苦了！

作者: fuke 时间: 2019-2-14 13:17

回复 fuke 的帖子

一个小公司没有任何利润居然存活了二十多年，也是不容易了，数据应该不会是假的。他们也不是上市公司，假数据也没有什么意义

作者: newchinabok 时间: 2019-2-14 15:50

本帖最后由 newchinabok 于 2019-2-14 16:23 编辑

StephenW 发表于 2019-2-14 12:10
回复 mingbai 的帖子

不要失望. 论坛中有很多偏见. 由于Replicor的临床试验，现在已经认识到降低血清HBsAg ...

rep2139ca怎么样了？？如同中国的乙克还在研究一样，呵呵

作者: StephenW 时间: 2019-2-14 17:29

回复 newchinabok 的帖子

要了解REP9AC各种版本的开发(REP2055, REP2139Ca, REP2139Mg, REP2165Mg)，您必须了解有关NAP的更多知识. Replicor发表的论文解释了其中许多.
Ca代表钙(Calcium)，Mg代表镁(Magnesium).
NAPs are phosphorothioated oligonucleotides (PS-ONs)NAP是硫代磷酸酯寡核苷酸（PS-ONs).
PS-ONs增加尿液中的矿物质消除.
所以REP9AC改进，以消除输注(infusion)副作用，缩短输注时间, 提高稳定性等等.
现在最好的版本是 REP 2139-Mg.
REP 2139-Mg将转变为皮下注射.

rep2139ca怎么样了？改良了!

作者: newchinabok 时间: 2019-2-14 17:45

StephenW 发表于 2019-2-14 17:29
回复 newchinabok 的帖子

要了解REP9AC各种版本的开发(REP2055, REP2139Ca, REP2139Mg, REP2165Mg)，您必 ...

能用就够了，不改良就不能治病了吗？

作者: newchinabok 时间: 2019-2-14 17:47

本帖最后由 newchinabok 于 2019-2-14 17:55 编辑

rep2139mg还可以改良，企不是永远上不了市，永远的二期，你觉得这个逻辑说得通吗？就像干挠素一样，难道等长效出来，才能治乙肝吗？如果是这样逻辑，2g手机根本不能上市，要等5g，6g……手机改良后才能上市用，这不滑稽可笑吗？

作者: 齐欢畅 时间: 2019-2-14 18:47

replicor公司的药物是否在clinicaltrail的网站上有登记记录？他的实验结果是否有真实性？这个其实可以查查就知道了。

作者: 齐欢畅 时间: 2019-2-14 18:50

Row Saved Status Study Title Conditions Interventions Locations
1

Active, not recruiting A Long Term Follow-up Study of Patients From the REP 301 Protocol
Hepatitis B, Chronic
Hepatitis D, Chronic
Infectious Clinical Hospital (n.a. Toma Ciorba)
Chisinau, Moldova, Republic of
2

Completed Combination Treatment With REP 2139-Ca and Pegasys in Patients With Chronic Hepatitis B
Hepatitis B, Chronic
Drug: REP 2139-Ca
Drug: pegylated interferon
Drug: entecavir
3

Completed Therapeutic Safety and Efficacy of REP 2139 (REP 9AC') in HBV Infected Patients
Hepatitis B, Chronic
Drug: REP 2139-Ca
Drug: Zadaxin
Drug: Pegasys
Farabi General Hospital
Dhaka, Bangladesh
4

Completed Therapeutic Safety and Efficacy of REP 9AC (REP 2055) in HBV or HCV Infected Patients
Hepatitis B, Chronic
Drug: REP 2055
Farabi General Hospital
Dhaka, Bangladesh
5

Active, not recruiting REP 2139-Mg and REP 2165-Mg Combination Therapy in Chronic Hepatitis B Infection
Chronic Hepatitis B
Drug: REP 2139-Mg
Drug: Pegasys
Drug: Viread
Drug: REP 2165-Mg
Infectious Clinical Hospital (n.a. Toma Ciorba) Department 5
Chisinau, Moldova, Republic of
Infectious Clinical Hospital (n.a. Toma Ciorba), Department 4
Chisinau, Moldova, Republic of
Repiblican Clinical Hospital (ARENSIA unit)
Chisinau, Moldova, Republic of
6

Completed REP 2139-Ca / Pegasys™ Combination Therapy in Hepatitis B / Hepatitis D Co-infection
Chronic HBV Infection (HBeAg Negative)
Drug: REP 2139-Ca + Pegasys (TM)
Infectious Clinical Hospital ( n.a. Toma Ciorba)
Chisinau, Moldova, Republic of

作者: 齐欢畅 时间: 2019-2-14 18:51

https://clinicaltrials.gov/ct2/r ... amp;city=&dist=

作者: 齐欢畅 时间: 2019-2-14 18:52

Trial record 1 of 1 for: REP 401
Previous Study | Return to List | Next Study
REP 2139-Mg and REP 2165-Mg Combination Therapy in Chronic Hepatitis B Infection

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02565719
Recruitment Status  : Active, not recruiting
First Posted  : October 1, 2015
Last Update Posted  : September 27, 2017
Sponsor:
Replicor Inc.
Information provided by (Responsible Party):
Replicor Inc.

Study Details Tabular ViewNo Results PostedDisclaimerHow to Read a Study Record
Study Description
Go to  sections
Brief Summary:
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 agent pegylated interferon-alpha 2a 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 open label, randomized and controlled 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.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis B
Drug: REP 2139-Mg
Drug: Pegasys
Drug: Viread
Drug: REP 2165-Mg
Phase 2

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 pegylated interferon alpha 2a. 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 pegylated interferon alpha-2a and improved control of HBV infection in the presence of tenofovir disoproxil fumarate (TDF). All patients will receive 24 weeks of monotherapy with TDF prior to entry into experimental or active comparator arms.

Study Design
Go to  sections
Study Type  : Interventional  (Clinical Trial)
Actual Enrollment  : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Randomized, Active Controlled, Parallel Comparison Study of the Safety and Efficacy of REP 2139-Mg in Combination With Pegasys® and Viread® and REP 2165-Mg in Combination With Pegasys® and Viread® in Patients With HBeAg Negative Chronic Hepatitis B
Study Start Date  : March 2016
Estimated Primary Completion Date  : September 2018
Estimated Study Completion Date  : March 2019
Resource links provided by the National Library of Medicine
MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B
Drug Information available for: Tenofovir Peginterferon Alfa-2a Tenofovir Disoproxil Tenofovir Disoproxil Fumarate
U.S. FDA Resources

Arms and Interventions
Go to  sections
Arm Intervention/treatment
Experimental: REP 2139-Mg with Viread and Pegasys
REP 2139-Mg in combination with tenofovir disoproxil fumarate (Viread) and pegylated interferon alpha-2a (Pegasys).
Drug: REP 2139-Mg
REP 2139-Mg = magnesium chelate complex of REP 2139
Other Name: not availalble

Drug: Pegasys
immunotherapy
Other Name: pegylated interferon alpha-2a

Drug: Viread
HBV RT polymerase inhibitor
Other Name: tenofovir disoproxil fumarate

Experimental: REP 2165-Mg with Viread and Pegasys
REP 2165-Mg in combination with tenofovir disoproxil fumarate (Viread) and pegylated interferon alpha-2a (Pegasys).
Drug: Pegasys
immunotherapy
Other Name: pegylated interferon alpha-2a

Drug: Viread
HBV RT polymerase inhibitor
Other Name: tenofovir disoproxil fumarate

Drug: REP 2165-Mg
REP 2165-Mg = magnesium chelate complex of REP 2165
Other Name: unaivalable

Active Comparator: Viread and Pegasys with crossover to REP 2139-Mg and Pegasys
Tenofovir disoproxil fumarate (Viread) and pegylated interferon alpha-2a (Pegasys) - crossover into add-on REP 2139-Mg therapy (triple combination) in patients with < 3 log reduction in serum HBsAg from baseline after 24 weeks of Pegasys exposure.
Drug: REP 2139-Mg
REP 2139-Mg = magnesium chelate complex of REP 2139
Other Name: not availalble

Drug: Pegasys
immunotherapy
Other Name: pegylated interferon alpha-2a

Drug: Viread
HBV RT polymerase inhibitor
Other Name: tenofovir disoproxil fumarate

Active Comparator: Viread and Pegasys with crossover to REP 2165-Mg and Pegasys
Tenofovir disoproxil fumarate (Viread) and pegylated interferon alpha-2a (Pegasys) - crossover into add-on REP 2165-Mg therapy (triple combination) in patients with < 3 log reduction in serum HBsAg from baseline after 24 weeks of Pegasys exposure.
Drug: Pegasys
immunotherapy
Other Name: pegylated interferon alpha-2a

Drug: Viread
HBV RT polymerase inhibitor
Other Name: tenofovir disoproxil fumarate

Drug: REP 2165-Mg
REP 2165-Mg = magnesium chelate complex of REP 2165
Other Name: unaivalable

Outcome Measures
Go to  sections

Primary Outcome Measures  :
Number of patients with adverse events [ Time Frame: 48 or 72 weeks (treatment duration) + 48 weeks (follow-up) ]
Patients will be assessed weekly for adverse events including symptoms and laboratory abnormalities

Secondary Outcome Measures  :
Number of patients with reduction of serum HBsAg [ Time Frame: Every two weeks for 48 or 72 weeks (treatment duration) + 48 weeks (follow-up) ]
The primary action of NAPs is to lower serum HBsAg. This effect is monitored throughout treatment and for 48 weeks following treatment.

Number of patients with controlled HBV infection following treatment [ Time Frame: 48 weeks follow-up (after completion of 48 or 72 weeks of treatment) ]
The synergistic antiviral effect of HBsAg removal and immunotherapy has restored immunological control of HBV mono-infection in human patients which has persisted after treatment was stopped. The persistence of immunological control of HBV infection observed in this study will be followed for 48 weeks after treatment has stopped.

Eligibility Criteria
Go to  sections

Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:    18 Years to 55 Years (Adult)
Sexes Eligible for Study:    All
Accepts Healthy Volunteers:    No
Criteria
Inclusion Criteria:
Signed Written Informed Consent
Males or females 18-55 years of age
HBsAg> 1000 IU / ml at screening
HBV DNA > 10000 copies / ml at screening
Seronegative for HIV, HCV, CMV (IgM) and HDV (anti-HDAg) as determined at screening visit
HBeAg negative, anti-HBe positive
Evidence of liver fibrosis at screening
Non cirrhotic: absence of advanced cirrhosis based on fibroscan evaluation at screening.
Willingness to utilize adequate contraception while being treated with REP 2139-Mg or REP 2165-Mg and for 6 months following the end of the treatment in the study
Any woman of childbearing potential (WOCBP) who agrees to use an effective methods of birth control for the entire duration of the study.
Sexually active men who agree to use an effective method of birth control if their partners are WOCBP for the entire duration of the study for 6 months following the end of treatment.
Body Mass Index (BMI) ≥ 18 kg/m2 and ≤ 30kg/m2 at screening (http://www.nhlbisupport.com/bmi/bmicalc.htm)
Adequate venous access allowing weekly intravenous therapies and blood tests
Exclusion Criteria:
Women with positive serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG).
Breast-feeding women.
HBeAg positive as determined at screening visit
Positive HCV antibody, or HIV-1/HIV-2 or CMV antibody (IgM) or anti-HDV antibody test at screening
Evidence of chronic liver disease caused by diseases other than chronic HBV infection (such as but not limited to: severe NAFLD, Wilson's disease, hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, significant biliary disease, nonalcoholic hepatic steatosis and toxin exposure).
Medical History and Concurrent Diseases
Current evidence of or history of variceal hemorrhage, hepatic encephalopathy, or ascites requiring diuretics or paracentesis or evidence of any of these findings on physical examination performed at screening
Documented or suspected HCC as evidenced by previously obtained imaging studies or liver biopsy.
Current evidence of or history of pancreatitis
Current evidence of or history of renal dialysis, including hemodialysis or peritoneal dialysis
History of bone marrow or organ transplant (other than cornea or hair), including liver transplant, or therapy with an immunomodulatory agent, cytotoxic agent, or systemic corticosteroids within 2 months of screening
Current or known history of cancer (except adequately treated in situ carcinoma of the cervix, or basal or squamous cell carcinoma of the skin) within 5 years prior to screening
Subjects with clinically significant ECG abnormalities (indicative of arrhythmia, myocardial ischemia or other serious cardiovascular disorder) at the time of screening in the opinion of the investigator
Active substance abuse, such as alcohol, or inhaled or injected drugs, as defined by Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), Diagnostic Criteria for Drug and Alcohol Abuse (see Appendix 1) within 12 months prior to screening.
The use of illicit drugs within the past two years prior to screening.
Prior or current history of cardiomyopathy or significant ischemic cardiac or cerebrovascular disease, including history of angina, myocardial infarction, or interventional procedure for coronary artery disease (including angioplasty, stent procedure, or cardiac bypass surgery)
Confirmed uncontrolled hypertension (patients with screening systolic blood pressure > 160 mmHg or diastolic blood pressure > 100 mmHg should be excluded unless discussed with Replicor Inc.)
Presence of diabetes (controlled or uncontrolled).
Prior or current history of clinically significant hemoglobinopathy or hemolytic anemia
History of or evidence of hyperthyroidism at screening.
Subjects with pre-existing ophthalmologic disorders considered clinically significant on eye exam during physical examination.
Prior or current history of severe chronic obstructive pulmonary disease, interstitial lung disease or sarcoidosis
History of immunologically mediated disease (including but not limited to, rheumatoid arthritis, inflammatory bowel disease, moderate to severe psoriasis [mild psoriasis is allowed], and systemic lupus erythematosus)
History of or current severe psychiatric disease, especially untreated or unstable depression, psychotic disorder such as bipolar disease and history of hospitalization for suicidal ideation/attempt
Active seizure disorder as defined by either untreated seizure disorder or continued seizure activity within the past year prior to screening despite treatment with anti-seizure medication
Has, in the opinion of the investigator, any physical exam findings, laboratory abnormalities, or other medical, social, or psychosocial factors that may negatively impact compliance or subject's safety by participation in this study; this should include conditions which may affect hematologic parameters such as prior or current history of porphyria cutanea tarda and/or hemophilia
Fibroscan and Fibromax showing current evidence advanced cirrhosis at screening or known history of decompensated cirrhosis based on radiologic criteria or biopsy results and clinical criteria
Poor venous access making IV infusion too difficult
Inability to provide informed consent
Inability or unwillingness to provide weekly blood samples.
Patients not willing to come every week to receive therapy or to give blood.
Physical and Laboratory Test Findings
Evidence of significant heavy metal load in whole blood as determined at pre-screening visit.
Antinuclear antibody (ANA) titer ≥ 1:640, AMA or LKM-1antibody positive as determined at pre-screening visit
Hemoglobin < 12.0 g/dL (males), < 10.0 g/dL (female) at screening
Platelet count < 90,000/mm3as determined at screening visit
Creatinine clearance (CrCl) (as estimated by Cockcroft and Gault) ≤50 mL/min or confirmed creatinine persistently>1.5 mg/dl as determined at screening visit
Total serum bilirubin>25umol/L as determined at screening visit.
INR ≥ 2.0 as determined at screening visit
PTT ≥ 2.0 x ULN as determined at screening visit
Serum albumin ≤ 3.5 g/dL (35 g/L) as determined at screening visit
ALT >10x ULN as determined at screening visit
ANC ≤ 1,500 cells/mm3 as determined at screening visit
Diagnosed or suspected hepatocellular carcinoma as evidenced by screening alpha-fetoprotein (AFP) of ≥ 100 ng/mL. If AFP is ≥ 50 ng/mL and < 100 ng/mL, absence of mass/findings suspicious for HCC must be demonstrated by ultrasound/CT/MRI within the screening period.
Diabetes mellitus as evidenced by HbA1C ≥ 8.5% at screening
QTc interval > 500 msec.
Known hypersensitivity to drugs with a similar biochemical structure to REP 2139-Mg or REP 2165-Mg (e.g. other phosphorothioate oligonucleotides) or Pegasys® (e.g. other interferons), Zadaxin® or Viread® (e.g. other nucleoside analog polymerase inhibitors such as entecavir).
Any other criteria or known contraindication that would exclude the subject from receiving REP 2139-Mg, REP 2165-Mg, Pegasys® or Viread®.
Prisoners or subjects who are involuntarily incarcerated.
Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
Employees, family members, or students of the investigator or clinical site
Individuals who participated in another clinical study of a medicinal product or medical device within 90 days of signing Informed Consent Form
Concomitant Treatments with any of the following medications:
Heparin
Coumadin
Blood products within 30 days prior to study enrollment
Hematologic growth factors within 90 days prior to study enrollment
Use of any investigational product within 1 year prior to study enrollment
Systemic antibiotics, antifungals, or antivirals for treatment of active infection within 14 days of enrollment.
Previous exposure to immunotherapy with 6 months prior to enrollment.
Contacts and Locations
Go to  sections

Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02565719

Locations
Moldova, Republic of
Infectious Clinical Hospital (n.a. Toma Ciorba) Department 5
Chisinau, Moldova, Republic of, 2004
Infectious Clinical Hospital (n.a. Toma Ciorba), Department 4
Chisinau, Moldova, Republic of, 2004
Repiblican Clinical Hospital (ARENSIA unit)
Chisinau, Moldova, Republic of, 2025
Sponsors and Collaborators
Replicor Inc.
Investigators
Principal Investigator: Victor Pantea, M.D. Infectious Diseases Department, State University of Medicine and Pharmacy, Infectious Clinical Hospital (n.a. Toma Clorba), Chisinau, Moldova, Republic of 2004
More Information
Go to  sections

Publications:
Noordeen F, Vaillant A, Jilbert AR. Nucleic acid polymers inhibit duck hepatitis B virus infection in vitro. Antimicrob Agents Chemother. 2013 Nov;57(11):5291-8. doi: 10.1128/AAC.01003-13. Epub 2013 Aug 12.
Noordeen F, Vaillant A, Jilbert AR. Nucleic acid polymers prevent the establishment of duck hepatitis B virus infection in vivo. Antimicrob Agents Chemother. 2013 Nov;57(11):5299-306. doi: 10.1128/AAC.01005-13. Epub 2013 Aug 12.

Responsible Party: Replicor Inc.
ClinicalTrials.gov Identifier: NCT02565719    History of Changes
Other Study ID Numbers: REP 401
First Posted: October 1, 2015 Key Record Dates
Last Update Posted: September 27, 2017
Last Verified: September 2017

作者: 齐欢畅 时间: 2019-2-14 18:54

clinicaltrail网站上登记的药物试验可以造假结果吗？？这一点我很想知道。

作者: 齐欢畅 时间: 2019-2-14 18:57

同样找到箭头公司的药物实验。  ARO-HBV

Trial record 1 of 1 for: ARO-HBV
Previous Study | Return to List | Next Study
Study of ARO-HBV in Normal Adult Volunteers and Patients With Hepatitis B Virus (HBV)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03365947
Recruitment Status  : Recruiting
First Posted  : December 8, 2017
Last Update Posted  : January 9, 2019
See Contacts and Locations
Sponsor:
Arrowhead Pharmaceuticals
Information provided by (Responsible Party):
Arrowhead Pharmaceuticals

Study Details Tabular ViewNo Results PostedDisclaimerHow to Read a Study Record
Study Description
Go to  sections
Brief Summary:
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of single- and multiple-ascending doses of ARO-HBV in healthy adult volunteers and participants with hepatitis B virus (HBV).

Condition or disease Intervention/treatment Phase
Hepatitis B
Drug: ARO-HBV Injection
Other: Sterile Normal Saline (0.9% NaCl)
Phase 1
Phase 2

Study Design
Go to  sections
Study Type  : Interventional  (Clinical Trial)
Estimated Enrollment  : 102 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 1/2a Single Dose-Escalating Study to Evaluate the Safety, Tolerability and Pharmacokinetic Effects of ARO-HBV in Normal Adult Volunteers and Multiple Escalating Doses Evaluating Safety, Tolerability and Pharmacodynamic Effects in HBV Patients
Actual Study Start Date  : March 27, 2018
Estimated Primary Completion Date  : March 30, 2019
Estimated Study Completion Date  : January 30, 2020
Resource links provided by the National Library of Medicine
MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B
U.S. FDA Resources

Arms and Interventions
Go to  sections
Arm Intervention/treatment
Active Comparator: ARO-HBV Injection Drug: ARO-HBV Injection
Single or multiple doses of ARO-HBV Injection by subcutaneous (sc) injection

Placebo Comparator: Placebo Other: Sterile Normal Saline (0.9% NaCl)
Calculated volume to match active comparator

Outcome Measures
Go to  sections

Primary Outcome Measures  :
Number of Participants With Adverse Events (AEs) Possibly or Probably Related to Treatment [ Time Frame: Up to 203 days ]

Secondary Outcome Measures  :
Pharmacokinetics (PK) of ARO-HBV: Maximum Observed Plasma Concentration (Cmax) [ Time Frame: Part A (single-ascending dose [SAD] phase) only: up to 48 hours post-dose ]
PK of ARO-HBV: Time to Maximum Plasma Concentration (Tmax) [ Time Frame: Part A (SAD phase) only: up to 48 hours post-dose ]
PK of ARO-HBV: Area Under the Plasma Concentration Versus Time Curve From Zero to 24 Hours (AUC0-24) [ Time Frame: Part A (SAD phase) only: up to 48 hours post-dose ]
PK of ARO-HBV: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUCinf) [ Time Frame: Part A (SAD phase) only: up to 48 hours post-dose ]
PK of ARO-HBV: Terminal Elimination Half-Life (t½) [ Time Frame: Part A (SAD phase) only: up to 48 hours post-dose ]
Reduction of HBV Surface Antigen (HBsAg) from Day 1 Pre-Dose Baseline to Post-Dose Nadir in Participants Chronically Infected With HBV [ Time Frame: Part B (multiple-ascending dose [MAD] phase) only: up to 113 days ]

Eligibility Criteria
Go to  sections

Information from the National Library of Medicine
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:    18 Years to 65 Years (Adult, Older Adult)
Sexes Eligible for Study:    All
Accepts Healthy Volunteers:    Yes
Criteria
Inclusion Criteria for Parts A & B:
Women of childbearing potential must have a negative pregnancy test, cannot be breast feeding, and must be willing to use contraception.
Willing to provide written informed consent and comply with study requirements
Additional Inclusion Criteria for Part B:
Diagnosis of chronic HBV infection
HbsAg at screening > or = 50 IU/mL
Liver Elastography score < or = 10.5
Exclusion Criteria:
Clinically significant health concerns (with the exception of HBV for Patients in Part B)
Abnormal for any clinical safety laboratory result considered clinically significant
Regular use of alcohol within 1 month prior to screening
Recent use of illicit drugs
Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study
NOTE: additional inclusion/exclusion criteria may apply, per protocol
Contacts and Locations
Go to  sections

Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03365947

Contacts
Contact: James Hamilton, MD 626-304-3400 [email protected]

Locations
Australia, New South Wales
Royal Prince Alfred Hospital Recruiting
Camperdown, New South Wales, Australia, 2050
Contact: Susan Hoy + 61295157383 [email protected]
Principal Investigator: Simone Strasser, MD
Australia, Victoria
Monash Medical Centre Recruiting
Clayton, Victoria, Australia, 3168
Contact: Sherryne Warner + 61395943081 [email protected]
Principal Investigator: William Sievert, MD
St. Vincent's Hospital Recruiting
Melbourne, Victoria, Australia, 3065
Contact: Eleanor Cropp +61392883594 [email protected]
Principal Investigator: Alexander Thompson, MD
Australia, Western Australia
Linear Research Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Shashi Aggarwal + 61432605618 [email protected]
Principal Investigator: Wendy Cheng, MD
Hong Kong
Queen Mary Hospital Recruiting
Hong Kong, Hong Kong
Contact: Ringo Wu + 85222553579 [email protected]
Principal Investigator: Man-fung Yuen, MD
New Zealand
Auckland Clinical Studies Limited Recruiting
Grafton, Auckland, New Zealand, 1010
Contact: Christian Schwabe, MD +64-9-3733474 [email protected]
Principal Investigator: Edward Gane, MD
Middlemore Clinical Trials Recruiting
Papatoetoe, Auckland, New Zealand, 2025
Contact: Amy Cryer +64 (0)9 276 0044 ext 2170 [email protected]
Principal Investigator: Tien Huey Lim, MD
Sponsors and Collaborators
Arrowhead Pharmaceuticals
More Information
Go to  sections

Responsible Party: Arrowhead Pharmaceuticals
ClinicalTrials.gov Identifier: NCT03365947    History of Changes
Other Study ID Numbers: AROHBV1001
First Posted: December 8, 2017 Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Hepatitis
Hepatitis B
Liver Diseases
Digestive System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human

作者: 齐欢畅 时间: 2019-2-14 19:01

StephenW 发表于 2019-2-14 12:10
回复 mingbai 的帖子

不要失望. 论坛中有很多偏见. 由于Replicor的临床试验，现在已经认识到降低血清HBsAg ...

作者: 齐欢畅 时间: 2019-2-14 19:02

StephenW 发表于 2019-2-14 12:10
回复 mingbai 的帖子

不要失望. 论坛中有很多偏见. 由于Replicor的临床试验，现在已经认识到降低血清HBsAg ...

clinicaltrail网站上登记的药物试验可以造假结果吗？？这一点我很想知道。

作者: newchinabok 时间: 2019-2-14 19:13

本帖最后由 newchinabok 于 2019-2-14 19:19 编辑

齐欢畅发表于 2019-2-14 19:02
clinicaltrail网站上登记的药物试验可以造假结果吗？？这一点我很想知道。 ...

你知道clinicaltrail的网站是什么性质的网站吗？像药渡一样收集的数据库之类。rep二期永远没有结果，都不了了之了

作者: newchinabok 时间: 2019-2-14 19:25

ClinicalTrials.gov作为临床研究登记的主要网站，为病人、医疗人员、研究者提供了大量疾病的临床研究信息。
该网站由NIH和FDA合作创建于2000年2月，目前已登记了来自50个州和200个国家的244933项临床研究。

作者: newchinabok 时间: 2019-2-14 19:26

本帖最后由 newchinabok 于 2019-2-14 19:34 编辑

齐欢畅发表于 2019-2-14 19:02
clinicaltrail网站上登记的药物试验可以造假结果吗？？这一点我很想知道。 ...

就是一个登记的网站。其实是太想治愈自己的疾病，宁可信其有，不可信其无，懒得去分析，探讨真伪，不愿面对真像的心态做遂，寻找一点心理安慰，可是总也等不来上市，rep宣传13年了吧，13年前都治愈乙肝，呵呵

作者: StephenW 时间: 2019-2-14 19:39

newchinabok 发表于 2019-2-14 17:47
rep2139mg还可以改良，企不是永远上不了市，永远的二期，你觉得这个逻辑说得通吗？就像干挠素一样，难道等 ...

"永远的二期" - 这是你自己的偏见. 药不是你的, 他们要改善, 无需咨询你, 不需要你的批准.

作者: newchinabok 时间: 2019-2-14 19:43

本帖最后由 newchinabok 于 2019-2-14 19:48 编辑

StephenW 发表于 2019-2-14 19:39
"永远的二期" - 这是你自己的偏见. 药不是你的, 他们要改善, 无需咨询你, 不需要你的批准. ...

你不能客观分析，也听不进反对声音，算不算偏见？时间和实践来回答。被情感蒙寐了双眼，你永远解释不了为什么一直改良，而不上市，就算三期都进不了的原因。我只不过是皇帝新装里讲真话的小孩罢了，说出了皇帝光着屁股在大街走的真像

作者: 齐欢畅 时间: 2019-2-14 19:48

StephenW 发表于 2019-2-14 19:39
"永远的二期" - 这是你自己的偏见. 药不是你的, 他们要改善, 无需咨询你, 不需要你的批准. ...

辩无胜

作者: newchinabok 时间: 2019-2-14 19:50

齐欢畅发表于 2019-2-14 19:48
辩无胜

根本不需辩，时间和实践说明一切。就如乙克，小韩一样成了笑柄

作者: StephenW 时间: 2019-2-14 19:54

回复 newchinabok 的帖子

你的意见"永远的二期" - 不是客观分析, 不合逻辑, 我认为是偏见.

作者: newchinabok 时间: 2019-2-14 19:57

StephenW 发表于 2019-2-14 19:54
回复 newchinabok 的帖子

你的意见"永远的二期" - 不是客观分析, 不合逻辑, 我认为是偏见. ...

我们都来看看这三年rep的三期试验。

作者: fuke 时间: 2019-2-14 20:57

回复 newchinabok 的帖子

那么这家公司一直做假数据，有什么意义呢？公司运营，二期实验都是花掉很多钱，作假也没有任何收入，我觉得肯定是有希望的，至少他们没有放弃。

作者: newchinabok 时间: 2019-2-14 21:07

本帖最后由 newchinabok 于 2019-2-14 21:18 编辑

fuke 发表于 2019-2-14 20:57
回复 newchinabok 的帖子

那么这家公司一直做假数据，有什么意义呢？公司运营，二期实验都是花掉很多钱， ...

做假都有意义，这基本道理都不懂吗，利益二字，a股为什么造假，我们中国的淘宝商品为什么造假？为什么乐复能忽悠，为什么国产药要一致性评价，为什么小韩要……你说为什么？

作者: wolegequ 时间: 2019-2-14 21:28

提示: 作者被禁止或删除内容自动屏蔽

作者: 齐欢畅 时间: 2019-2-14 22:02

作者: newchinabok 时间: 2019-2-14 23:00

本帖最后由 newchinabok 于 2019-2-14 23:01 编辑

wolegequ 发表于 2019-2-14 21:28
分析真假就应该用理论和数据来推翻Rep的pdf数据，有公开数据和研究的，这样会更好沟通吧?
而不是认为一直2 ...

公众不可能了解内幕，只能分析。你的想法不靠谱，只能透过现象看本质

作者: 灵魂不屈 时间: 2019-2-15 07:54

是不是这个药的作用机制他们自己始终没有搞清楚？一直在研究。

作者: pourvivre 时间: 2019-2-15 08:24

本帖最后由 pourvivre 于 2019-2-14 19:29 编辑

REP 确有其药而且效果应该不错我听过我的主治医生谈过。而且他们还在研究和改进。我几年前在本地地铁广告里也见过他们招实验病人，给报酬的。至于原因，不要多说了，他的疗法要配合TDF和干扰素，那么生产后两种药的人，是不是这家小公司的股东或者之一之二呢？将来还可能配合其他更能刺激免疫或者抗病毒的药物呢？？他们会决定何时推出这个东西的以适应整体利益。这是商业机密。资本主义社会，办企业成本不菲，依靠知识产权和法律保护的专利来谋利，而不是单纯忽悠造假，加拿大目前行业监管的大环境制度下，没有那么多奴性的专业人员愿意配合造假，为了短期的利益毁了自己的长期职业生涯和生活。西方社会的卖家和买家都是逻辑思维+理性思维，不是靠忽悠和冲动行事的。我相信这个药效果正在改进中。

作者: newchinabok 时间: 2019-2-15 08:32

本帖最后由 newchinabok 于 2019-2-15 08:43 编辑

pourvivre 发表于 2019-2-15 08:24
REP 确有其药而且效果应该不错我听过我的主治医生谈过。而且他们还在研究和改进。我几年前在本地地铁广 ...

又回到sw老师逻辑上来了，一直在改进，永远不上市。rep2139ca改进成rep2139mg，呵呵，你知道rep9ac版本治愈乙肝效果吗？，知道会惊了你，不改进不能治病吗？那临床病人去哪了？

作者: hao2014 时间: 2019-2-15 08:48

回复 pourvivre 的帖子

还有一种可能

正是基于你文中提到的：
他的疗法要配合TDF和干扰素，那么生产后两种药的人，是不是这家小公司的股东或者之一之二呢？将来还可能配合其他更能刺激免疫或者抗病毒的药物呢？？他们会决定何时推出这个东西的以适应整体利益。

也就是把已经上市的药物的潜力都榨干了，市场萎缩了，再推出新的药物

TAF就是前车之鉴

这个过程，也许几年，也许十几年，某种意义上，这是不造假的造假

作者: pourvivre 时间: 2019-2-15 09:00

本帖最后由 pourvivre 于 2019-2-14 20:12 编辑

回复 hao2014 的帖子

商业总是复杂的，药物研究和生产商以自己最大利益作为研发动力，没有错，别人没资格要求商人是道德家，商人在不伤害他人利益前提下，以最大化牟利作为动机才最能服务社会。
打个比方，萝卜炖海参能治疗乙肝。REP现在只是个萝卜价，要配着干扰素这个海参来治病。卖萝卜不赚钱啊！所以他就想找到怎么把萝卜高价卖给海参商人来治愈乙肝，把这个套餐申请成专利，卖出海参价格，或者找个成本低的白菜，一旦萝卜白菜套餐治愈率高，就拿萝卜白菜套餐申请专利，和白菜商协议发财计划，两人合伙卖出海参价，这样才有商业意义。
总之，他们的治疗思路还是不错的。也许他们压根不想卖药，而是一边慢慢做实验，一边积累数据，同时不断申请专利，不断展销和宣传，等着大鱼们上钩，然后等着转让天价专利给生产TDF和干扰素或者其他药物的药商来作为治愈套餐呢？商业和内幕我们就多猜测了，病人自己想着怎么治病，他们继续研究试验来提高治愈率，来提高贩售专利的报价，对病人来说，看到有潜力的治愈药物在路上，是件好事。

作者: newchinabok 时间: 2019-2-15 09:25

本帖最后由 newchinabok 于 2019-2-15 09:29 编辑

箭头RNAi+tdf+免疫药组合更真实，更靠谱，箭头也是降hbdag，也是二期，abus和箭头都在探索研究，更值得大家关注，rep只不过是海市蜃楼罢了，只不过是正能量充值罢了

作者: fuke 时间: 2019-2-15 11:58

回复 newchinabok 的帖子

箭头的是一期，arb1467已经被放弃了。现在也就是衣壳抑制剂进展快点

作者: 左罗 时间: 2019-2-15 11:59

个人认为无关本质的争论或讨论可否先放一下，现在当务之急是：受蹉跎岁月折磨的乙人们最大的期盼，无论什么治愈药，只要能解决该死的HBsAg,只要能早点出研究成果，只要能早点上市普渡众生。真的就谢天谢地了！

作者: newchinabok 时间: 2019-2-15 13:41

fuke 发表于 2019-2-15 11:58
回复 newchinabok 的帖子

箭头的是一期，arb1467已经被放弃了。现在也就是衣壳抑制剂进展快点 ...

箭头公司乙肝基因疗法-ARO-HBV的I/II期研究结果喜人
Jerry编译药事纵横 2018-11-14
❈❈
⬥ARO-HBV可使乙肝病毒表面抗原水平（HBsAg）平均降低1.9 Log10（98.7%）
⬥在每月400 mg的剂量下，ARO-HBV具有良好的耐受性。
9月9日，Arrowhead制药公司公布了第3代皮下注射RNA干扰药物，ARO-HBV的I/II期研究（代号AROHBV1001）的初步临床数据。ARO-HBV作为一种慢性乙型肝炎病毒（HBV）的潜在治疗手段，目前正处于研究开发阶段。AROHBV1001所得到的重要的最新数据将会在肝脏会议的最新海报上呈现出来，此次会议为美国肝病研究协会年度会议，将在旧金山举行。

健康受试者接受单剂量ARO-HBV或安慰剂（n=30）的初步结果，以及慢性乙型肝炎患者接受3个月ARO-HBV联用恩替卡韦或替诺福韦（NUC类药物）可获得至少6周的HBsAg（n=24）的结果，这些数据如下：
● 每月皮下注射超过400 mg单剂量或者多剂量的ARO-HBV呈现出较好的耐受性，大约12%的皮下注射可观察到轻微的注射部位反应。
● 在所有的HBV患者中均有强烈的HBsAg反应。
HBsAg水平平均降低1.9 Log10（98.7%）
HBsAg水平降低范围为1.3（95%）至3.8（99.98%）
●乙肝e抗原（HBeAg）阳性和HBeAg阴性患者中HbsAg反应减少的情况相似。
在HBeAg阳性患者中（n=11），HBsAg水平平均降低2.1 Log10
在HBeAg阴性患者中（n=13），HBsAg水平平均降低1.8 Log10
●初次使用NUC类药物（n=8）和已服用过NUC类药物（n=9）的患者中，HbsAg反应减少的情况相似。
队列8中（n=4），HBsAg水平在第57天平均降低1.7 Log10
队列9中（n=4），HBsAg水平在第57天平均降低1.9 Log10
● 这一结果充分表明了ARO-HBV是在Arrowhead制药公司第一代仅靶向作用于来自共价闭合环状DNA（cccDNA）的RNA干扰（RNAi）治疗HBV的药物ARC-520这一基础上的一次突破（Wooddell,2018）。
● ARO-HBV所观察到的HbsAg反应与ARO-HBV干扰来自于cccDNA的HBV mRNA以及宿主整合病毒DNA的能力相一致。
●这些反应在所有其他病毒学参数（HBV DNA，HBV RNA，HBeAg，HBcrAg）中均能观察到。
Arrowhead首席运营官兼研发负责人Bruce Given博士表示，“在AROHBV1001研究中，ARO-HBV仍继续在所有的HBV患者中呈现高水平的活性，此外，ARO-HBV的耐受性特征也支持了其后续的研究。ARO-HBV后续的开发及商业化，我们将与Janssen合作，我们都有一个共同的目标，那就是推进转化药物，使得HBV患者在有限的治疗时间内获得更高的治疗率。”
关于AROHBV1001
AROHBV1001（NCT03365947）是一项I/II期研究，用来评估单次递增剂量ARO-HBV对健康成年志愿者的安全性，耐受性和药代动力学影响，以及评估多次递增剂量ARO-HBV对慢性乙肝患者的安全性，耐受性和药效学效应。
单剂量递增研究已经完成，包括了35mg，100mg, 200mg, 300mg, 400mg等5个剂量的队列研究。多次剂量递增研究正在进行中，包括了3个月连续注射25mg,50mg，100mg,200mg，300mg以及400 mg的队列研究。近期又增加了25 和50 mg的队列研究，且为了更好地表征ARO-HBV剂量反应关系，队列规模增加到n=8，此项研究也在评估每周或者每两周给予一次药物是否有额外的效果。AROHBV1001试验设计招募30名健康志愿者以及72名以上的HBV患者。
中期报告分析结果表明，所有单剂量健康受试者队列及起初的慢性乙肝患者队列中，每个月接受ARO-HBV，HBsAg检测水平超过6周。
这里我们报告了所有健康受试者的安全性和耐受性，及慢性乙肝患者第2b-5b、8和9组安全性、耐受性和病毒学测定。第2b-5b组为HBeAg阳性或阴性，基线为初次使用NUC类药物或已使用过NUC类药物的患者，第8和9组均为HBeAg阳性患者，且分别是初次使用NUC类药物和已使用过NUC类药物的患者，在整个研究过程中，已使用过NUC类药物的患者则继续服用，初次使用NUC类药物的患者则在试验开始第一天起每天服用NUC类药物。
信息来源：Arrowhead制药公司

作者: 左罗 时间: 2019-2-15 14:19

回复 newchinabok 的帖子

这药魔力确实不小哟！不知Arrowhead此药目前是否正在进行I期或是II期呢？如果是II期，大概试验数据能否在今年下半年得知吗？

作者: fuke 时间: 2019-2-15 14:29

回复左罗的帖子

还在一期阶段

作者: newchinabok 时间: 2019-2-15 14:30

左罗发表于 2019-2-15 14:19
回复 newchinabok 的帖子

这药魔力确实不小哟！不知Arrowhead此药目前是否正在进行I期或是II期呢？如果是I ...

查美国临床试验网和官网

作者: hao2014 时间: 2019-2-15 20:05

回复 pourvivre 的帖子

商业总是复杂的，药物研究和生产商以自己最大利益作为研发动力，没有错，别人没资格要求商人是道德家，商人在不伤害他人利益前提下，以最大化牟利作为动机才最能服务社会。

你这里面的几个关键词，你自己看到了没有？？

作者: 齐欢畅 时间: 2019-2-15 23:30

欢迎光临肝胆相照论坛 (http://hbvhbv.info/forum/)