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Oral Antivirals (GS-5885, Tegobuvir, and/or GS-9451) With Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection

2014年1月14日 更新者：Gilead Sciences

A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy Using Combinations of Oral Antivirals (GS-5885, Tegobuvir, and/or GS-9451) With Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol GS US 256 0124)

This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy using Combinations of Oral Antivirals (GS-5885, tegobuvir, and/or GS-9451) with Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects with Chronic Genotype 1 Hepatitis C Virus (HCV) Infection.

研究概览

地位

完全的

条件

干预/治疗

详细说明

In September 2011, the FDA requested that Gilead make several major changes to this study because of side effects experienced by two patients in other Gilead studies.

In 2 HCV-infected people that were given tegobuvir with another experimental medication plus interferon and ribavirin, big reductions in the number of white blood cells, red blood cells and platelets were seen. Because these cases might have been related to tegobuvir when given with interferon, ribavirin and another direct antiviral agent, tegobuvir is no longer being given to people with these other medications in this study.

As a result, the study is now open label which means both you and your study doctor will know the medication you will be receiving and Arms 1 and 3 have been discontinued from the study.

All subjects enrolled in the study as of September 2nd 2011 will receive Response Guided Therapy (RGT) with both GS-5885 and GS-9451 plus PEG and RBV.

研究类型

介入性

注册 (实际的)

163

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 波多黎各
      • San Juan、波多黎各、00927
        • Fundacion De Investigacion de Diego
  • 美国
    • Alabama
      • Dothan、Alabama、美国、36305
        • Digestive Health Specialists Of The Southeast
      • Montgomery、Alabama、美国、36116
        • Alabama Liver and Digestive Specialists
    • California
      • Beverly Hills、California、美国、90211
        • California Liver Institute
      • La Jolla、California、美国、92037
        • Scripps Clinic
      • Sacramento、California、美国、95817
        • University of California Davis Medical Center
      • San Diego、California、美国、92123
        • Medical Associates Research Group
      • San Diego、California、美国、92154
        • Kaiser Permanente
      • San Diego、California、美国、92015
        • RESEARCH and EDUCATION, INC
    • Colorado
      • Aurora、Colorado、美国、80045
        • University of Colorado Denver
      • Englewood、Colorado、美国、80110
        • South Denver Gastroenterology
    • Florida
      • Bradenton、Florida、美国、34209
        • Bach and Godofsky Infectious Diseases
      • Gainesville、Florida、美国、32610
        • University of Florida
      • Miami、Florida、美国、33136
        • University of Miami
      • Orlando、Florida、美国、32803
        • Orlando Immunology Center
      • Wellington、Florida、美国、33414
        • South Florida Center of Gastroenterology, LLC
    • Georgia
      • Atlanta、Georgia、美国、30309
        • Digestive Healthcare of Georgia
      • Atlanta、Georgia、美国、30308
        • Emory University, Infectious Disease Clinic
      • Decatur、Georgia、美国、30033
        • Dekalb Gastroenterology
      • Marietta、Georgia、美国、30060
        • Gastrointestinal Specialists of Georgia PC
    • Indiana
      • Indianapolis、Indiana、美国、46202
        • Indiana University
      • Indianapolis、Indiana、美国、46237
        • Indianapolis Gastroenterology Research Foundation
    • Kentucky
      • Bowling Green、Kentucky、美国、42101
        • Graves Gilbert Clinic
    • Louisiana
      • Baton Rouge、Louisiana、美国、70809
        • Gastroenterology Associates, LLC
    • Maryland
      • Baltimore、Maryland、美国、21229
        • Digestive Disease Associates, PA
    • Massachusetts
      • Boston、Massachusetts、美国、02115
        • Beth Israel Deaconess Medical Center
      • Worcester、Massachusetts、美国、01608
        • Partners in Internal Medicine, P.C.
    • Michigan
      • Detroit、Michigan、美国、48202
        • Henry Ford Health System
    • Mississippi
      • Jackson、Mississippi、美国、39202
        • Gastrointestinal Associates, PA
      • Tupelo、Mississippi、美国、38801
        • Digestive Health Specialists, PA
    • New Jersey
      • Hillsborough、New Jersey、美国、08844
        • ID Care 105
      • Morristown、New Jersey、美国、07960
        • Atlantic Research Affiliates, LLC
    • New Mexico
      • Santa Fe、New Mexico、美国、87505
        • Southwest CARE Center
    • New York
      • Binghamton、New York、美国、13903
        • Binghamton Gastroenterology
      • Manhasset、New York、美国、11030
        • North Shore University Hospital
      • New York、New York、美国、10016
        • Concorde Medical Group
      • New York、New York、美国、10021
        • Cornell University Gastroenterology & Hepatology
    • North Carolina
      • Asheville、North Carolina、美国、28801
        • Asheville Gastroenterology Associates, P.A.
      • Durham、North Carolina、美国、27710
        • Duke University Medical Center
      • Fayetteville、North Carolina、美国、28304
        • Cumberland Research Associates, LLC
    • Ohio
      • Cincinnati、Ohio、美国、45267
        • University of Cincinnati
    • Oklahoma
      • Tulsa、Oklahoma、美国、74104
        • Options Health Research, LLC
    • Rhode Island
      • Providence、Rhode Island、美国、02905
        • University Gastroenterology
    • Tennessee
      • Germantown、Tennessee、美国、38138
        • Memphis Gastroenterology Group
      • Nashville、Tennessee、美国、37205
        • Nashville Medical Research Institute
      • Nashville、Tennessee、美国、37211
        • Nashville Gastrointestinal Specialists, Inc
      • Nashville、Tennessee、美国、37203
        • Columbia Medical Group, The Frist Clinic
    • Texas
      • Arlington、Texas、美国、76012
        • The North Texas Research Institute
      • Dallas、Texas、美国、75246
        • Baylor University Medical Center
      • Houston、Texas、美国、77005
        • Kelsey Research Foundation
      • Houston、Texas、美国、77030
        • Research Specialists of Texas
    • Virginia
      • Fairfax、Virginia、美国、22031
        • Metropolitan Research
      • Norfolk、Virginia、美国、23502
        • Digestive and Liver Disease Specialists
      • Richmond、Virginia、美国、23249
        • Liver Institute of Virginia
    • Washington
      • Seattle、Washington、美国、98101
        • Virginia Mason Medical Center, Digestive Disease Institute

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 80年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Male or female, aged from 18 to 70 years old, inclusive
  • Chronic HCV infection for at least 6 months prior to Baseline
  • Subjects must have liver biopsy results (≤ 3 years prior to screening) indicating the absence of cirrhosis.
  • Monoinfection with HCV genotype 1
  • HCV RNA > 10^4 IU/mL at Screening
  • Prior treatment and adherence (as defined by receiving at least 80% of the prescribed treatment) with one course of a pegylated interferon-alfa (Pegasys or Peg-Intron) and RBV

  • The subject's medical records must include sufficient detail of prior treatment with pegylated interferon-alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either

    • Non-Responder: Subject did not achieve undetectable HCV RNA levels during or at the end of a treatment period of at least 12 weeks duration. Within Nonresponders, subjects will be further defined as Null or Partial Responders if they had < 2 log10 or ≥ 2 log10 reduction, respectively, in HCV RNA during the first 12 weeks of treatment
    • Responder: Subject achieved undetectable HCV RNA during treatment. Within Responders, subjects will be further defined as Relapsers if they had undetectable HCV RNA at the end of at least 42 weeks of treatment but detectable HCV RNA levels observed within 1 year of the end of treatment and Breakthrough subjects if they achieved undetectable HCV RNA levels during the treatment period but detectable HCV RNA at the end of treatment.
  • No prior treatment with an oral HCV antiviral (exclusive of RBV).
  • Body mass index (BMI) 18-36 kg/m2, inclusive.
  • Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula) ≤ 450 msec for males and ≤ 470 msec for females
  • Creatinine clearance ≥ 50 mL/min.
  • Agree to use two forms of highly effective contraception for the duration of the study and for 6 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at Screening and Baseline

Exclusion Criteria:

  • Discontinued prior treatment with pegylated interferon-alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up.
  • Exceed defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH)
  • Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), or another HCV genotype, hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
  • Current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone are excluded, however stable buprenorphine maintenance treatment for at least 6 months is not exclusionary
  • Receiving any of the prohibited concomitant medications.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Arm 2

AM Dosing: One GS-5885 30 mg tablet, two GS-9451 100 mg tablets, orally with RBV and with food.

PM Dosing: RBV with food.

PEG, 180 µg, will be administered weekly by subcutaneous injection for the specified period of time (see Study Design). Pegasys® prefilled syringes (Hoffman-La Roche) will be supplied by Gilead Sciences.
药品：GS-5885 tablet
30 mg active tablet
药品：GS-9451 tablet
two active 100 mg tablets
生物：peginterferon alfa-2a
peginterferon alfa-2a (solution for injection) 180 µg/week
药品：ribavirin tablet
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Sustained Virologic Response (SVR)
大体时间：through 24 weeks of off-treatment follow-up
To evaluate antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA < Lower Limit of Quantification (LLoQ) 24 weeks post-treatment) of response guided therapy (RGT) with GS-9451 + GS-5885, with peginterferon alfa-2a (PEG) and ribavirin (RBV) in treatment-experienced subjects.
through 24 weeks of off-treatment follow-up

次要结果测量

结果测量
措施说明
大体时间
Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks
大体时间：Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment
To evaluate antiviral efficacy as measured by SVR for 24 or 48 weeks of treatment with GS-5885, GS-9451, PEG, RBV.
Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment
Safety and Tolerability
大体时间：through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
To evaluate the safety and tolerability of treatment with GS-5885, GS-9451, PEG & RBV administered for 24 or 48 weeks. Safety endpoints will be summarized as the number (proportion) of subjects with events or abnormalities for categorical values or as an 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment arm.
through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
Characterize the viral dynamics of GS-5885, GS-9451 when administered in combination with PEG and RBV
大体时间：Through Week 2 of therapy
HCV RNA levels, pharmacokinetics, and viral sequencing
Through Week 2 of therapy
Characterize the pharmacokinetics of GS-5885 and GS-9451 when administered in combination with PEG and RBV
大体时间：Through Week 2 of therapy
Plasma concentrations of the study drug over time will be summarized using descriptive statistics. Pharmacokinetic parameters (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed and summarized for GS-5885 and GS-9451, using descriptive statistics (eg, sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and maximum).
Through Week 2 of therapy
Emergence of Viral Resistance
大体时间：through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up
To characterize the viral resistance to GS-5885 and GS 9451tegobuvir when administered in combination with PEG and RBV.
through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Gilead Sciences

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2011年7月1日

初级完成 (实际的)

2013年3月1日

研究完成 (实际的)

2013年3月1日

研究注册日期

首次提交

2011年6月9日

首先提交符合 QC 标准的

2011年6月10日

首次发布 (估计)

2011年6月13日

研究记录更新

最后更新发布 (估计)

2014年2月11日

上次提交的符合 QC 标准的更新

2014年1月14日

最后验证

2014年1月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • GS-US-256-0124

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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