Trial record 1 of 1 for: REP 2139
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REP 2139-Ca / Pegasys™ Combination Therapy in Hepatitis B / Hepatitis D Co-infection
This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by REPLICor Inc.
Sponsor:
REPLICor Inc.
Information provided by (Responsible Party):
REP 2139-Ca is nucleic acid polymer. Nucleic acid polymers have been previously shown to clear serum hepatitis B virus surface antigen (HBsAg) both preclinically (in duck HBV infected ducks) and in human patients and to act synergistically with immunotherapeutic agents such as pegylated interferon-alpha 2a or thymosin alpha-1 to restore host immunological control of HBV infection.
HBsAg is an essential component of the hepatitis D virus (HDV), therefore the direct action of REP 2139-Ca in removing serum HBsAg and its synergistic effect with pegylated interferon-alpha 2a is expected to have a significant antiviral effect against HDV infection.
This study will examine the safety and efficacy of REP 2139-Ca therapy when used in combination with pegylated interferon alpha-2a in patients with HBV / HDV co-infection.
The primary hypothesis to be tested is that this combined dosing regimen is safe and well tolerated in patients with HBV / HDV co-infection which will be assessed by examining the number of patients with adverse events (including reported symptoms and laboratory abnormalities).
The secondary hypothesis to be tested is that this combined dosing regimen will have an antiviral effect against HBV / HDV co-infection in these patients which will be assessed by examining the following outcomes:
The number of patients with reductions in serum HBsAg.
The number of patients with reductions in serum HDAg and HDV RNA
The number of patients that experience a sustained antiviral response after treatment is stopped (reductions in serum HBV DNA and HDV RNA).
The secondary hypothesis to be tested is that this combination approach can have an effective
Condition Intervention Phase
Hepatitis B With Hepatitis D Superinfection
Drug: REP 2139-Ca + Pegasys (TM)
Phase 2
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Study of the Safety and Efficacy of Combination Treatment With REP 2139-Ca and Pegasys™ in Patients With Hepatitis B / Hepatitis D Co-infection
Tracking Information
First Received Date ICMJE September 1, 2014
Last Updated Date September 27, 2014
Start Date ICMJE September 2014
Estimated Primary Completion Date May 2016 (final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE
(submitted: September 5, 2014) Number of patients experiencing a treatment-related adverse event. [ Time Frame: Every week for 63 weeks. ] [ Designated as safety issue: Yes ]
Will examine the hypothesis that combined REP 2139-Ca / Pegasys(TM) treatment is safe and well tolerated in patients with HBV / HDV co-infection
Original Primary Outcome Measures ICMJE Same as current
Change History Complete list of historical versions of study NCT02233075 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE
(submitted: September 5, 2014)
Number of patients with reduction of serum HBsAg. [ Time Frame: Every two weeks for 63 weeks (treatment duration) + 24 weeks (follow-up) ] [ Designated as safety issue: No ]
Will examine the hypothesis that combination treatment with REP 2139-Ca / Pegasys(TM) will have an antiviral effect in patients with HBV / HDV co-infection.
Number of patients with reduced serum HDV antigen / HDV RNA [ Time Frame: Every two weeks for 63 weeks (treatment duration) + 24 weeks followup ] [ Designated as safety issue: No ]
Will examine the hypothesis that combination treatment with REP 2139-Ca / Pegasys(TM) will have an antiviral effect in patients with HBV / HDV co-infection.
Number of patients with controlled HBV / HDV infection following treatment [ Time Frame: 24 weeks follow up (after completion of 63 weeks of treatment) ] [ Designated as safety issue: No ]
Will examine the hypothesis that combination treatment with REP 2139-Ca / Pegasys(TM) will have an antiviral effect in patients with HBV / HDV co-infection.
Original Secondary Outcome Measures ICMJE Same as current
Current Other Outcome Measures ICMJE Not Provided
Original Other Outcome Measures ICMJE Not Provided
Descriptive Information
Brief Title ICMJE REP 2139-Ca / Pegasys™ Combination Therapy in Hepatitis B / Hepatitis D Co-infection
Official Title ICMJE A Study of the Safety and Efficacy of Combination Treatment With REP 2139-Ca and Pegasys™ in Patients With Hepatitis B / Hepatitis D Co-infection
Brief Summary
REP 2139-Ca is nucleic acid polymer. Nucleic acid polymers have been previously shown to clear serum hepatitis B virus surface antigen (HBsAg) both preclinically (in duck HBV infected ducks) and in human patients and to act synergistically with immunotherapeutic agents such as pegylated interferon-alpha 2a or thymosin alpha-1 to restore host immunological control of HBV infection.
HBsAg is an essential component of the hepatitis D virus (HDV), therefore the direct action of REP 2139-Ca in removing serum HBsAg and its synergistic effect with pegylated interferon-alpha 2a is expected to have a significant antiviral effect against HDV infection.
This study will examine the safety and efficacy of REP 2139-Ca therapy when used in combination with pegylated interferon alpha-2a in patients with HBV / HDV co-infection.
The primary hypothesis to be tested is that this combined dosing regimen is safe and well tolerated in patients with HBV / HDV co-infection which will be assessed by examining the number of patients with adverse events (including reported symptoms and laboratory abnormalities).
The secondary hypothesis to be tested is that this combined dosing regimen will have an antiviral effect against HBV / HDV co-infection in these patients which will be assessed by examining the following outcomes:
The number of patients with reductions in serum HBsAg.
The number of patients with reductions in serum HDAg and HDV RNA
The number of patients that experience a sustained antiviral response after treatment is stopped (reductions in serum HBV DNA and HDV RNA).
The secondary hypothesis to be tested is that this combination approach can have an effective
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 results in the rapid and effective clearance of HBsAg 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.
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 or thymosin alpha-1 to stimulate recovery of complete immune control of HBV infection.
HDV superinfection can only occur in patients with HBV infection because HDV requires the HBsAg protein for its assembly. Therefore, it is expected that the removal of serum HBsAg (from HBV SVPs) and unmasking of the anticipated, pre-existing anti-HBsAg response by REP 2139 will result in the clearance of HBV and HDV from the blood. Furthermore, the enhanced effect of immunotherapy in the absence of serum HBsAg has the potential to provide a durable control of both HBV and HDV infection that will persist after treatment.
Study Type ICMJE Interventional
Study Phase Phase 2
Study Design ICMJE Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Condition ICMJE Hepatitis B With Hepatitis D Superinfection
Intervention ICMJE Drug: REP 2139-Ca + Pegasys (TM)
15 weeks of REP 2139-Ca (500mg QW IV) followed by: 15 weeks of REP 2139-Ca (250mg QW IV) + Pegasys(TM) (180 ug QW SC) followed by: 33 weeks of Pegasys(TM) (180 ug QW SC)
Other Name: Pegasys(TM) = pegylated interferon alpha-2a
Study Arm (s) Experimental: REP 2139-Ca + Pegasys (TM)
REP 2139-Ca 500 mg QW for 15 weeks followed by REP 2139-Ca 250mg QW + Pegasys(TM) 180ug QW for 15 weeks followed by Pegasys(TM) 180ug QW for 33 weeks.
Intervention: Drug: REP 2139-Ca + Pegasys (TM)
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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE Recruiting
Estimated Enrollment ICMJE 12
Estimated Completion Date July 2016
Estimated Primary Completion Date May 2016 (final data collection date for primary outcome measure)
Eligibility Criteria ICMJE
Inclusion Criteria:
Age between 18 and 55 years
HBsAg > 1000 IU / ml
HDAg+
HDV RNA +
No detectable antibodies to HIV, HCV or CMV.
Non cirrhotic
Willingness to utilize adequate contraception while being treated with REP 213-Ca and for 6 months following the end of treatment
Adequate venous access allowing weekly intravenous therapies and blood tests
Body Mass Index (BMI) ≥ 18 kg/m2 and ≤ 25 kg/m2
Exclusion Criteria:
Evidence of cardiovascular disease
Evidence of autoimmune hepatitis
Presence of Wilson's disease
Presence of severe NAFLD
Evidence of any other co-existent liver disease
ANA (anti-nuclear antibody) positive
Fibroscan and Fibromax showing evidence of advanced cirrhosis.
Any history of ascites, hepatic encephalopathy or variceal hemorrhage
Body weight > 100 kg
Platelet count < 90,000, PMN count < 1,500 or HCT < 33%
Evidence of significant heavy metal load in whole blood.
AFP > 100 ng/ml or the presence of a hepatic mass suggestive of HCC
Bilirubin above the normal range
ALT > 5x ULN
Creatinine > 1.5 mg/dl
Serum albumin < 35 mg/ml
The presence of diabetes (whether controlled or uncontrolled)
Another serious medical disorder
A serious psychiatric disorder
Evidence of hypertension
A history of alcohol abuse within the last year
The use of illicit drugs within the past two years
Inability to provide informed consent
Inability or unwillingness to provide weekly blood samples
Poor venous access making IV infusion too difficult
Patient not willing to come every week to receive therapy
Gender Both
Ages 18 Years to 55 Years
Accepts Healthy Volunteers No
Contacts ICMJE
Listed Location Countries ICMJE Moldova, Republic of
Removed Location Countries
Administrative Information
NCT Number ICMJE NCT02233075
Other Study ID Numbers ICMJE REP 301
Has Data Monitoring Committee No
Responsible Party REPLICor Inc.
Study Sponsor ICMJE REPLICor Inc.
Collaborators ICMJE Not Provided
Investigators ICMJE
Principal Investigator: Victor Pantea, MD Infectious Diseases Department, State University of Medicine and Pharmacy
Information Provided By REPLICor Inc.
Verification Date September 2014
No Study Results Posted on ClinicalTrials.gov for this Study
About Study Results Reporting on ClinicalTrials.gov
Study Status: This study is currently recruiting participants.
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure) 作者: 阳光醉人 时间: 2015-2-8 08:04
本帖最后由 阳光醉人 于 2015-2-8 08:08 编辑
目的
代表2139 CA核酸聚合物。核酸聚合物已经显示出明确的血清乙型肝炎病毒表面抗原（HBsAg）在临床前（鸭乙肝病毒感染的鸭子），在人类患者和协同作用的免疫治疗剂，如聚乙二醇干扰素α-2a或胸腺肽α1恢复HBV感染的宿主免疫控制
HBsAg的丁型肝炎病毒（HDV）的一个重要组成部分，因此在去除血清HBsAg和聚乙二醇干扰素α-2a的协同效应代表2139 CA直接行动预计将有一个对HDV感染显著的抗病毒作用
本研究将检查的安全性和疗效的代表2139治疗CA的使用与聚乙二醇干扰素α-2a治疗乙肝/ HDV感染的组合
要测试的主要假设是，这种联合给药方案与乙肝/ HDV感染的不良事件检查病人数评估患者是安全和耐受性良好（包括报告的症状和实验室异常）。
要测试的假设是，这次联合用药方案将在这些患者中，将通过以下的评估结果对乙肝/ HDV感染的抗病毒作用：
在血清HBsAg下降的患者人数。
一些患者血清HDAg和HDV RNA的减少
患者经历持续的抗病毒治疗停止后数（血清HBV DNA和RNA HDV的减少）。
要测试的假设是，这二相结合的方法可以有一个有效的
条件干预阶段
乙型肝炎和丁型肝炎重叠感染
代表药物：2139钙+派罗欣（TM）
2期
研究类型：介入
研究设计：端点分类：安全/疗效研究
干预模式：单组分配
掩蔽：开放标签
主要用途：治疗
标题：官方的安全和代表2139 CA和Pegasys™与乙型肝炎、丁型肝炎合并感染的患者联合治疗的疗效研究
资源链接提供的信息：
一个存放相关专题：甲型肝炎乙型肝炎
对可用的药物信息：聚乙二醇干扰素α-2
美国FDA的资源
进一步研究细节的复制子公司提供：：
主要成果的措施：
在经历了与治疗相关的不良事件的患者数。[时间框架：每63周。] [指定为安全问题：是]
将探讨的假设组合代表2139钙/派罗欣（TM）治疗乙肝/ HDV感染的患者是安全和耐受性良好
次要结果的措施：
随着血清HBsAg减少病人的数量。[时间框架：每两周为63周（处理时间）+ 24周（后续）] [指定为安全问题：无]
将研究假设与代表2139钙/派罗欣联合治疗（TM）将患者中具有抗病毒效果乙肝/ HDV重叠感染。
降低血清HDV抗原/ HDV RNA [时间框架的例数：每两周为63周（处理时间）+ 24周随访] [指定为安全问题：无]
将研究假设与代表2139钙/派罗欣联合治疗（TM）将患者中具有抗病毒效果乙肝/ HDV重叠感染。
与控制乙肝/ HDV感染后的治疗[时间框架的例数：24周随访（治疗63周后）] [指定为安全问题：无]
将研究假设与代表2139钙/派罗欣联合治疗（TM）将患者中具有抗病毒效果乙肝/ HDV重叠感染。
估计人数：12
研究开始日期：九月2014
估计研究的完成日期：七月2016
初步估计完工日期：2016（最后的主要结果测量数据采集日期）
武器分配干预
实验：代表2139的Ca +派罗欣（TM）
代表2139钙500毫克QW 15周后重复2139钙250mg QW +派罗欣（TM）180ug QW 15周后派罗欣（TM）180ug QW 33周。
代表药物：2139钙+派罗欣（TM）
15周重复2139钙（500mg QW IV）依次为：15周代表2139 CA（250mg QW IV）+派罗欣（TM）（180μs的SC）依次为：33周的派罗欣（TM）（180μs的SC
其他名称：派罗欣（TM）=聚乙二醇干扰素α-2
详细说明：
核酸聚合物（NAP）利用硫代寡核苷酸的序列独立性为目标的载脂蛋白相互作用参与HBV亚病毒颗粒的形成（SVP），主要包括乙肝表面抗原（HBsAg）。午睡的作用是阻止感染的肝细胞内，防止其分泌SVP的形成。作为SVP帐户>；血液中的乙肝表面抗原99.99%，午睡是清除HBV感染患者血清HBsAg的有效途径。
先前的临床试验表明，治疗与NAP REP 2139结果快速、有效的清除血液中的乙肝表面抗原。这也揭露底层HBsAg清除的直接影响，已有的抗乙肝表面抗原（抗-HBs）反应，使HBV病毒从血液中清除。
HBsAg在HBV感染已列块的适应性和先天免疫过程中重要的免疫抑制作用。从患者的血液清除HBsAg消除这种抑制作用。
因此，从血液中清除HBsAg的另外一个重要作用是大大提高免疫治疗剂，如聚乙二醇干扰素α-2a或胸腺肽α1的影响刺激对HBV感染的免疫控制恢复完成
丁型肝炎病毒重叠感染只发生在HBV感染患者由于HDV需要装配HBsAg蛋白。因此，预计血清HBsAg的清除（HBV SVPS）和自己的预期，已有的抗HBsAg反应的代表2139会导致血液中的HBV和HDV的间隙。此外，增强的免疫治疗效果血清中HBsAg的缺失有可能提供一个持久的控制HBV和HDV感染，坚持治疗后。
资格
合资格的研究：18年至55年
性别学习的资格：两
接受健康志愿者：无
标准
纳入标准：
18岁和55岁之间
乙肝表面抗原>；1000 IU / ml
丁型肝炎抗原+
HDV RNA +
没有检测到HIV抗体，丙型肝炎病毒或巨细胞病毒。
非肝硬化
利用适当的避孕意愿时代表213 Ca和6个月的治疗结束后，治疗
足够的静脉通路允许每周静脉治疗及血液测试
身体质量指数（BMI）≥18 kg/m2和≤25公斤/平方米
排除标准：
心血管疾病的证据
自身免疫性肝炎的证据
Presence of Wilson’s病
NAFLD presence of severe
evidence of any other共存在liver disease
ANA阳性（抗核抗体）
Fibroscan and fibromax showing evidence of Advanced肝硬化。
any History of腹水，肝脑病或静脉曲张破裂失血
body weight >；100公斤
血小板计数中性粒细胞计数90000，<；<；< 1500 or HCT 33%；
evidence of significant重金属Load in全血。
法新社>；100毫微克/毫升or the presence of a mass of HCC肝暗示
bilirubin above the正常范围
5倍ULN ALT >；
肌酐>；1.5毫克/分升
血清白蛋白& lt；35毫克/毫升
糖尿病（the presence of whether or uncontrolled控制）
另一个严重的医学障碍
A Serious Psychiatric障碍
evidence of高血压
A History of酒精滥用within the last year
the use of非法毒品within the past two years
inability to provide informed consent
inability to provide or unwillingness周刊blood samples
可怜的静脉输液too difficult Access制作四
病人不愿意每周来接收治疗
接触和租赁
选择to participate in a study is an important个人的决定。谈话与您的医生和家庭成员或朋友about to join研究决定。学习more about this study，你或你的医生可能接触the study研究人员提供using the接触below。对于一般的信息，见了解临床研究。
Please refer to this study by its临床试验发现：nct02233075
租赁
摩尔多瓦共和国
传染性临床医院（N以ciorba）招聘
摩尔多瓦基希讷乌，共和国，2004
接触：维克多PANTEA，MD + 373 69 11 27 victorpantea”mail.ru
接触：情人节cebotarescu，MD + 373 79 46 50 51瓦伦丁_ cebotarescu @雅虎网站
主要研究人员：维克多PANTEA，MD
赞助商和合作者
replicor公司。
investigators
主要研究人员：维克多PANTEA，MD Infectious diseases Department，州立大学现代医学杂志
更多的信息
出版物：
noordeen F，勇敢，jilbert AR。nucleic酸性聚合物inhibit鸭乙型肝炎病毒感染的体外。医院感染药物化疗。2013年11月，57（11）：5291 - 8。我：10.1128 / aac.01003-13。收稿日期2013年8月12。
noordeen F，勇敢，jilbert AR。nucleic酸性聚合物prevent the establishment of鸭乙型肝炎病毒感染的体内。医院感染药物化疗。2013年11月（11）：5299；57页。我：10.1128 / aac.01005-13。收稿日期2013年8月12。
负责人：replicor公司。
临床试验发现：nct02233075 History of changes
其他研究ID号码：REP 301
研究第一received：September 1，2014年
Last updated：9月27日，2014年
卫生局：摩尔多瓦：药品局
摩尔多瓦：卫生部
摩尔多瓦国家伦理委员会
相关术语：额外的网格
coinfection
肝炎
A型肝炎
乙型肝炎
D型肝炎
重复感染
DNA病毒感染
digestive system diseases
肠道病毒感染
肝病毒感染
肝炎，病毒性，人权
感染
肝疾病
opportunistic感染
寄生病
小核糖核酸病毒感染
RNA病毒感染
病毒病
peginterferonα2
抗infective代理
抗病毒药物
pharmacologic股票
治疗性使用
临床试验处理这个记录我们February 05，2015年 作者: 阳光醉人 时间: 2015-2-8 08:12