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TMC278-TiDP6-C215: A Clinical Trial in Treatment Naive HIV-subjects Patients Comparing TMC278 to Efavirenz in Combination With 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

2016年3月3日 更新者：Tibotec Pharmaceuticals, Ireland

A Phase III, Randomized, Double-blind Trial of TMC278 25mg q.d. Versus Efavirenz 600mg q.d. in Combination With a Background Regimen Containing 2 Nucleoside/Nucleotide Reverse Transcriptase Inhibitors in Antiretroviral-naive HIV-1 Infected Subjects.

The purpose of this trial is to compare the effectiveness, safety and tolerability of TMC278 given at a dose of 25 mg once daily versus efavirenz (EFV) at a dose of 600 mg once daily, when combined with a background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors ( investigator choice of ABC/3TC, TDF/FTC or AZT/3TC) in HIV-1 infected patients who have not yet taken any anti-HIV drugs. The following evaluations will be done: antiviral activity, immunologic changes, and viral geno-/phenotype evolution, relationship of Pharmacokinetics (PK) and PK/Pharmacodynamics and Medical resource utilization and treatment adherence.

研究概览

地位

完全的

条件

干预/治疗

详细说明

Over the past decade, anti-human immunodeficiency virus (HIV) drugs have been introduced sequentially for use in the clinic. Currently, patients are routinely being treated with 3 or 4 drug combinations including nucleoside/tide analogue reverse transcriptase inhibitors (NRTIs/NtRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and/or fusion inhibitors. New potent antiretroviral (ARV) compounds that work in people whose HIV-1 virus is resistant to available drugs are urgently needed. This is a Phase III, randomized (study medication is assigned by chance), double-blind (neither the study physician nor the patient knows the name of the study assigned medication), double-dummy, active-controlled trial to compare the effectiveness, safety, and ability to tolerate TMC278 versus efavirenz (EFV). The study will last for 104 weeks which includes a screening period of 4 weeks, a 96-week treatment period, followed by a 4 week follow-up period. Patients will be randomly assigned (like tossing a coin) to TMC278 or to efavirenz in combination with two other anti-HIV drugs of the class nucleoside/nucleotide reverse transcriptase inhibitors. The hypothesis to be provided in this study is that the investigational drug TMC278 will perform just like efavirenz (EFV) in terms of antiviral effectiveness (i.e., suppressing of the plasma viral load to a level < 50 HIV-1 RNA (ribonucleic acid) copies/mL, in ARV-naïve HIV-infected patients. During the trial, patients' health will be monitored by physical examination, interview to assess health and well being, and laboratory testing on blood and urine samples. Experimental Group: One tablet of TMC278 25 mg daily; plus efavirenz (EFV) placebo; plus 2 nucleoside/nucleotide reverse transcriptase inhibitors; Control Group: One tablet of Placebo daily that looks just like TMC278 plus EFV 600 mg daily plus 2 nucleoside/nucleotide reverse transcriptase inhibitors for 104 weeks.

研究类型

介入性

注册 (实际的)

680

阶段

  • 第三阶段

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

  • 中国
      • Beijing、中国
      • Guangzhou、中国
      • Shanghai、中国
  • 俄罗斯联邦
      • Moscow N/A、俄罗斯联邦
      • Saint-Petersburg、俄罗斯联邦
      • Smolensk、俄罗斯联邦
      • Voronezh、俄罗斯联邦
  • 加拿大
    • Alberta
      • Calgary、Alberta、加拿大
    • British Columbia
      • Vancouver、British Columbia、加拿大
    • Manitoba
      • Winnipeg、Manitoba、加拿大
    • Ontario
      • Toronto、Ontario、加拿大
    • Quebec
      • Montreal、Quebec、加拿大
  • 南非
      • Bloemfontein、南非
      • Cape Town、南非
      • Dundee、南非
      • Johannesburg、南非
      • Pretoria N/A、南非
      • Westdene Johannesburg Gauteng、南非
  • 印度
      • Chennai、印度
      • Nagpur、印度
  • 哥斯达黎加
      • San Jose、哥斯达黎加
  • 墨西哥
      • Guadalajara N/A、墨西哥
      • Mexico City、墨西哥
  • 巴拿马
      • Panama、巴拿马
      • Panama City N/A、巴拿马
  • 巴西
      • Campinas、巴西
      • Distrito Barao Geraldo-Campina、巴西
      • Pinheiros、巴西
      • Recife、巴西
      • Sao Paulo、巴西
  • 德国
      • Berlin、德国
      • Essen、德国
      • Frankfurt、德国
      • Hamburg、德国
      • Hannover、德国
      • Köln、德国
      • Mannheim、德国
  • 智利
      • Providencia、智利
      • Santiago、智利
  • 比利时
      • Antwerpen、比利时
      • Brussels、比利时
      • Gent、比利时
      • Leuven、比利时
  • 法国
      • Clamart、法国
      • Le Kremlin Bicetre、法国
      • Montpellier、法国
      • Paris、法国
  • 波多黎各
      • San Juan、波多黎各
  • 泰国
      • Bangkok、泰国
  • 澳大利亚
      • Darlinghurst、澳大利亚
      • Prahran、澳大利亚
      • Surry Hills、澳大利亚
  • 美国
    • California
      • Long Beach、California、美国
      • Los Angeles、California、美国
      • San Francisco、California、美国
    • District of Columbia
      • Washington、District of Columbia、美国
    • Florida
      • Atlantis、Florida、美国
      • Miami、Florida、美国
      • Miami Beach、Florida、美国
      • Orlando、Florida、美国
      • Tampa、Florida、美国
    • Illinois
      • Chicago、Illinois、美国
    • Kentucky
      • Lexington、Kentucky、美国
    • Maryland
      • Baltimore、Maryland、美国
    • Massachusetts
      • Boston、Massachusetts、美国
      • Springfield、Massachusetts、美国
    • Michigan
      • Detroit、Michigan、美国
    • Minnesota
      • Minneapolis、Minnesota、美国
    • New Jersey
      • Newark、New Jersey、美国
    • New York
      • Bronx、New York、美国
      • Flushing、New York、美国
      • New York、New York、美国
      • Rochester、New York、美国
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国
    • Texas
      • Dallas、Texas、美国
      • Houston、Texas、美国
      • Longview、Texas、美国
  • 英国
      • London、英国
      • Manchester、英国
  • 葡萄牙
      • Porto、葡萄牙
  • 西班牙
      • Barcelona、西班牙
      • Barcelona N/A、西班牙
      • Elche、西班牙
      • Madrid、西班牙

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 99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:

  • Patient with documented HIV-1 infection
  • Patient has never been treated with a therapeutic HIV vaccine or an ARV drug prior to screening
  • Patient's HIV-1 plasma viral load at screening is > 5,000 HIV-1 RNA copies/mL (assayed by RNA PCR standard specimen procedure)
  • Patient's virus is sensitive to the 2 nucleoside/nucleotide reverse transcriptase inhibitors chosen for treatment
  • Patient agrees not to start ART before the baseline visit
  • Patient is HLA-B*5701 negative in case abacavir is included in the patient's treatment regimen.

Exclusion Criteria:

  • Previous use of ANY ARV drug for ANY length of time
  • Any documented evidence of NNRTI resistance associated mutations in patient's HIV
  • Category C AIDS defining illness, except, Stable Kaposi Sarcoma Wasting syndrome if not progressive
  • Pneumocystis carinii pneumonia (PCP) that is considered not cured
  • Active TB
  • Allergy or hypersensitivity to study or background ARTs
  • Specific grade 3 or 4 toxicity
  • Kidney impairment: calculated creatinine clearance <50 ml/min

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
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
有源比较器：002
efavirenz 600 mg tablet once daily for 96 weeks
药品：efavirenz
600 mg tablet once daily for 96 weeks
实验性的：001
TMC278 25 mg tablet once daily for 96 weeks
药品：TMC278
25 毫克片剂，每天一次，持续 96 周

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
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 48
大体时间：Week 48
Virological response is defined as confirmed plasma viral load less than (<) 50 human immunodeficiency virus-1 (HIV-1) (ribonucleic acid [RNA]) copies/milliliter (ml) at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 50 copies/ml after being responder) or who were never suppressed (no confirmed viral load <50 copies/ml).
Week 48

次要结果测量

结果测量
措施说明
大体时间
从基线到第 48 周和第 96 周的绝对和相对 CD4+ 细胞计数的平均变化（使用估算数据）
大体时间：基线、第 48 周和第 96 周
在缺失值的情况下估算 CD4+ 细胞计数相对于基线的变化：在过早停药的情况下，数据用停药后的基线值估算（即 change=0，未完成者 [NC] = 失败）；否则应用最后的观察结转。
基线、第 48 周和第 96 周
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 48
大体时间：Week 48
The analysis is based on the last observed viral load (VL) data within the Week 48 window. Virologic response is defined as a VL<50 copies/mL (observed case). Missing VL was considered as non-response. Virologic Failure includes subjects who had VL>=50 copies/mL in the Wk 48 window, subjects who discontinued early due to lack or loss of efficacy, subjects who discontinued for reasons other than an adverse event, death or lack or loss of efficacy and at the time of discontinuation had a VL>=50 copies/mL and subjects who had a switch in background regimen that was not permitted by the protocol.
Week 48
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <50 Copies Per mL) at Week 96
大体时间：Week 96
Week 96
Number of Participants With Virological Response (Intent-to-Treat - Snapshot, <50 Copies Per mL) at Week 96
大体时间：Week 96
Week 96
Number of Participants With Virological Response (Observed, <50 Copies/mL) at Last On-Treatment Visit (Post-Week 96).
大体时间：Variable, ranging from 3 months up to maximum 18 months for TMC278 and 12 months for Efavirenz
Virological response is defined as (observed) plasma viral load less than 50 human immunodeficiency virus-type 1 (HIV-1) ribonucleic acid (RNA) copies per mL at the last on-treatment post-Week 96 visit.
Variable, ranging from 3 months up to maximum 18 months for TMC278 and 12 months for Efavirenz
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 48
大体时间：Week 48
Virological response is defined as confirmed plasma viral load < 400 HIV-1 (RNA) copies/mL at Week 48. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load <400 copies/mL).
Week 48
Number of Participants With Virological Response (Intent-to-Treat - Time to Loss of Virologic Response [TLOVR], <400 Copies Per mL) at Week 96
大体时间：Week 96
Virological response is defined as confirmed plasma viral load < 400 HIV-1 (RNA) copies/mL at Week 96. The TLOVR algorithm was used to derive response. Response needed to be confirmed at 2 consecutive visits and participants who permanently discontinued were considered nonresponders after discontinuation. Resuppression after confirmed virologic failure was considered as failure. Virologic Failure includes participants who were rebounder (confirmed viral load >= 400 copies/mL after being responder) or who were never suppressed (no confirmed viral load <400 copies/mL).
Week 96
Number of Participants With Virologic Failure for the Resistance Determinations by Developing Mutations: First Available On-Treatment Genotypic Data After Failure
大体时间：Week 96
Virologic failure for the resistance determinations was defined as lack of virologic response (never having had 2 consecutive plasma viral load <50 copies/mL) and plasma viral load increase of >=0.5 log 10 copies/mL above nadir (i.e., never suppressed), or confirmed loss of virologic response (2 consecutive plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL; i.e., rebounder), or discontinued with a last observed on-treatment plasma viral load >=50 copies/mL after having had 2 consecutive plasma viral load <50 copies/mL. For this study, treatment-emergent reverse transcriptase (RT) resistance associated mutations (RAMs) occurring in at least 2 virologic failures (for at least one treatment group) for the following lists are presented: i) Extended list of Non-nucleoside reverse transcriptase inhibitor (NNRTI RAMs) ii) IAS-USA list of Nucleoside/tide reverse transcriptase inhibitor (N[t]RTI RAMs).
Week 96

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

Tibotec Pharmaceuticals, Ireland

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

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

2008年6月1日

初级完成 (实际的)

2010年1月1日

研究完成 (实际的)

2012年2月1日

研究注册日期

首次提交

2007年10月11日

首先提交符合 QC 标准的

2007年10月11日

首次发布 (估计)

2007年10月15日

研究记录更新

最后更新发布 (估计)

2016年4月1日

上次提交的符合 QC 标准的更新

2016年3月3日

最后验证

2016年3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

  • CR002704
  • TMC278-TIDP6-C215 (其他标识符：Tibotec Pharmaceuticals, Ireland)

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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