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Dose-finding Study of BMS-955176 to Treat HIV-1 Infected Treatment-naive Adults

2018年8月20日 更新者：ViiV Healthcare

A Phase 2b Randomized, Active-Controlled, Double-Blind Trial to Investigate Safety, Efficacy, and Dose-response of BMS-955176, Given on a Backbone of Tenofovir/Emtricitabine, in Treatment-Naive HIV-1 Infected Adults

The purpose of this study is to find at least one dose of BMS-955176 that will be safe, effective and tolerable for HIV-1 infected treatment naive adults.

研究概览

地位

终止

条件

干预/治疗

研究类型

介入性

注册 (实际的)

210

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

  • 加拿大
      • Quebec、加拿大、G1V 4G2
        • GSK Investigational Site
    • Alberta
      • Edmonton、Alberta、加拿大、T6G 2G3
        • GSK Investigational Site
    • Manitoba
      • Winnipeg、Manitoba、加拿大、R3A 1R9
        • GSK Investigational Site
    • Ontario
      • Ottawa、Ontario、加拿大、K1H 8L6
        • GSK Investigational Site
    • Quebec
      • Montreal、Quebec、加拿大、H3A 1T1
        • GSK Investigational Site
      • Montreal、Quebec、加拿大、H2L 4P9
        • GSK Investigational Site
      • Montreal、Quebec、加拿大、H4A 3J1
        • GSK Investigational Site
      • Montreal、Quebec、加拿大、H2L 5B1
        • GSK Investigational Site
  • 南非
    • Free State
      • Bloemfontein、Free State、南非、9301
        • GSK Investigational Site
  • 墨西哥
      • DF、墨西哥、14000
        • GSK Investigational Site
      • Durango、墨西哥、34000
        • GSK Investigational Site
      • Mexico City、墨西哥、CP 14080
        • GSK Investigational Site
    • Aguascalientes
      • Fracc. Las Americas、Aguascalientes、墨西哥、20020
        • GSK Investigational Site
    • Guanajuato
      • León、Guanajuato、墨西哥、37000
        • GSK Investigational Site
  • 德国
      • Berlin、德国、13353
        • GSK Investigational Site
      • Berlin、德国、12157
        • GSK Investigational Site
      • Dortmund、德国、44137
        • GSK Investigational Site
    • Bayern
      • Muenchen、Bayern、德国、80335
        • GSK Investigational Site
      • Muenchen、Bayern、德国、80336
        • GSK Investigational Site
    • Niedersachsen
      • Hannover、Niedersachsen、德国、30625
        • GSK Investigational Site
    • Nordrhein-Westfalen
      • Bonn、Nordrhein-Westfalen、德国、53127
        • GSK Investigational Site
      • Duesseldorf、Nordrhein-Westfalen、德国、40225
        • GSK Investigational Site
      • Essen、Nordrhein-Westfalen、德国、45122
        • GSK Investigational Site
  • 意大利
    • Lombardia
      • Bergamo、Lombardia、意大利、24127
        • GSK Investigational Site
      • Milano、Lombardia、意大利、20127
        • GSK Investigational Site
      • Milano、Lombardia、意大利、20157
        • GSK Investigational Site
      • Monza、Lombardia、意大利、20900
        • GSK Investigational Site
  • 智利
      • Santiago、智利、8360159
        • GSK Investigational Site
      • Santiago、智利、7560994
        • GSK Investigational Site
    • Región Metro De Santiago
      • Santiago、Región Metro De Santiago、智利
        • GSK Investigational Site
  • 法国
      • Le Kremlin-Bicêtre、法国、94276
        • GSK Investigational Site
      • Lyon cedex 04、法国、69317
        • GSK Investigational Site
      • Nantes、法国、44093
        • GSK Investigational Site
      • Nice、法国、06202
        • GSK Investigational Site
      • Paris、法国、75013
        • GSK Investigational Site
      • Paris、法国、75012
        • GSK Investigational Site
      • Paris Cedex 10、法国、75475
        • GSK Investigational Site
  • 波兰
      • Bydgoszcz、波兰、85-030
        • GSK Investigational Site
      • Szczecin、波兰、71-252
        • GSK Investigational Site
      • Warszawa、波兰、01-201
        • GSK Investigational Site
      • Wroclaw、波兰、50-220
        • GSK Investigational Site
  • 美国
    • California
      • Beverly Hills、California、美国、90211
        • GSK Investigational Site
      • Los Angeles、California、美国、90036
        • GSK Investigational Site
    • Florida
      • DeLand、Florida、美国、32720
        • GSK Investigational Site
    • Georgia
      • Atlanta、Georgia、美国、30312
        • GSK Investigational Site
      • Decatur、Georgia、美国、30033
        • GSK Investigational Site
    • New Mexico
      • Santa Fe、New Mexico、美国、87505
        • GSK Investigational Site
    • Oklahoma
      • Tulsa、Oklahoma、美国、74135
        • GSK Investigational Site
    • Texas
      • Fort Worth、Texas、美国、76104
        • GSK Investigational Site
  • 英国
      • London、英国、E1 1BB
        • GSK Investigational Site
      • London、英国、W2 1NY
        • GSK Investigational Site
      • London、英国、SW10 9NH
        • GSK Investigational Site
      • Tooting, London、英国、SW17 0QT
        • GSK Investigational Site
    • Midlothian
      • Edinburgh、Midlothian、英国、EH4 2XU
        • GSK Investigational Site
  • 西班牙
      • Alcala de Henares、西班牙、28805
        • GSK Investigational Site
      • Badalona、西班牙、08916
        • GSK Investigational Site
      • Madrid、西班牙、28040
        • GSK Investigational Site
      • Madrid、西班牙、28034
        • GSK Investigational Site
      • Santiago de Compostela、西班牙、15706
        • GSK Investigational Site
  • 阿根廷
      • Buenos Aires、阿根廷、1141
        • GSK Investigational Site
      • Buenos Aires、阿根廷、1202
        • GSK Investigational Site
      • Córdoba、阿根廷、X5000JJS
        • GSK Investigational Site
    • Buenos Aires
      • Ciudad Autonoma de Buenos Aires、Buenos Aires、阿根廷、C1181ACH
        • GSK Investigational Site
    • Santa Fe
      • Rosario、Santa Fe、阿根廷、2000
        • GSK Investigational Site

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 及以上 (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

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  • Men and non-pregnant women, at least 18 years of age
  • Antiretroviral treatment-naïve; defined as no current or previous exposure to > 1 week of an antiretroviral drug
  • Plasma HIV-1 RNA ≥ 1000 copies/mL
  • CD4 T-cell count > 200 cells/mm3

Exclusion Criteria:

  • Resistance or partial resistance to any study drug determined by tests at Screening
  • Current or historical genotypic and/or phenotypic drug resistance testing showing certain resistance mutations to EFV, TDF, FTC, Protease Inhibitors
  • Chronic hepatitis B virus (HBV)/ hepatitis C virus (HCV)
  • Blood tests that indicate normal liver function
  • Hemoglobin < 8.0 g/dL, platelets < 50,000 cells/mm3

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：三倍

武器和干预

参与者组/臂
干预/治疗
实验性的：Arm 1: BMS-955176 60 mg + TDF/FTC
BMS-955176 at 60 mg active dose per day + BMS-955176 placebo matching 120 mg + efavirenz (EFV) placebo matching 600 mg + tenofovir/emtricitabine (TDF/FTC) 300/200 mg per day, orally
药品：BMS-955176
HIV成熟抑制剂
药品：TDF/FTC
TDF/FTC
实验性的：Arm 2: BMS-955176 120 mg + TDF/FTC
BMS-955176 placebo matching 60 mg + BMS-955176 at 120mg active dose per day + EFV placebo matching 600mg + TDF/FTC 300/200mg per day, orally
药品：BMS-955176
HIV成熟抑制剂
药品：TDF/FTC
TDF/FTC
实验性的：Arm 3: BMS-955176 180 mg + TDF/FTC
BMS-955176 at 60mg active dose per day + BMS-955176 at 120mg active dose per day + EFV placebo matching 600mg + TDF/FTC at 300/200mg per day, orally
药品：BMS-955176
HIV成熟抑制剂
药品：TDF/FTC
TDF/FTC
有源比较器：Arm 4: EFV + TDF/FTC
BMS-955176 placebo matching 60mg + BMS-955176 placebo matching 120mg + EFV at 600mg per day + TDF/FTC 300/200mg per day
药品：TDF/FTC
TDF/FTC
药品：EFV
EFV

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 Plasma HIV-1 Ribonucleic Acid (RNA) <40 Copies Per Milliliter (c/mL) at Week 24 Using Food and Drug Administration (FDA) Snapshot Algorithm
大体时间：Week 24
Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV 1 RNA <40 c/mL at Week 24 using the FDA snapshot algorithm. This used the last on-treatment plasma HIV-1 RNA measurement within an FDA-specified visit window (18 to 30 weeks) to determine response. Analysis was performed on mITT Population, which comprised of randomized participants who received at least 1 dose of BMS-955176/GSK3532795 or EFV.
Week 24

次要结果测量

结果测量
措施说明
大体时间
Number of Participants With Plasma HIV-1 RNA < 40 c/mL at Weeks 48 and 96 Using FDA Snapshot Algorithm
大体时间：Weeks 48 and 96
Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV 1 RNA <40 c/mL at Weeks 48 and 96 using the FDA snapshot algorithm. This used the last on-treatment plasma HIV-1 RNA measurement within an FDA-specified visit window to determine response. The analysis was performed using mITT Population (observed), which consisted of participants in the mITT Population excluding participants who had no HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (10 October 2016). The data was not collected for Week 96 analysis; as the study was terminated early. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
Weeks 48 and 96
Number of Participants With Plasma HIV-1 RNA < 200 c/mL at Week 24 Using FDA Snapshot Algorithm
大体时间：Week 24
Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV-1 RNA <200 c/mL at Week 24 using the FDA snapshot algorithm. This used the last on-treatment plasma HIV-1 RNA measurement within an FDA-specified visit window to determine response.
Week 24
Number of Participants With Plasma HIV-1 RNA < 200 c/mL at Weeks 48 and 96
大体时间：Weeks 48 and 96
Blood samples were collected for quantitative analysis of plasma HIV-1 RNA. The antiviral efficacy was determined by the number of participants with plasma HIV-1 RNA <200 c/mL at Weeks 48 and 96 using the FDA snapshot algorithm. This used the last on-treatment plasma HIV-1 RNA measurement within an FDA-specified visit window to determine response. The analysis was performed using mITT Population (observed), which consisted of participants in the mITT Population excluding participants who had no HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (10 October 2016). The data was not collected for Week 96 analysis; as the study was terminated early. Only those participants with data available at the specified time points were analyzed (represented by n=X in category titles).
Weeks 48 and 96
Number of Participants With Newly Emergent Genotypic Resistance Using All On-treatment Isolates
大体时间：Week 24
The emergence of genotypic resistance among samples selected for drug resistance testing were assessed by searching for all reverse transcriptase substitutions and protease inhibitor substitutions listed in the International Acquired Immunodeficiency Syndrome (AIDS) Society-United States of America (IAS-USA) list of HIV-1 drug resistance mutations. The outcome was originally designed to be assessed up to 96 weeks of treatment, but it was analyzed up to Week 24 as the study was terminated early. The emergence of genotypic resistance is presented for participants in the mITT Population who had Baseline and on-treatment genotypic resistance testing and who had successful sequencing.
Week 24
Number of Participants With Newly Emergent Phenotypic Resistance Using All On-treatment Isolates
大体时间：Week 24
Phenotypic resistance to a drug is defined as a fold change (i.e., ratio of the 50% inhibitory concentration (IC50) of the clinical isolate to the IC50 of the reference strain) which is greater than the cut-off for reduced susceptibility. Emergent phenotypic resistance to BMS-955176/GSK3532795 was defined as a Baseline fold change IC50<= 3 and an on-treatment fold change IC50>3. The number of participants with newly emergent phenotypic resistance is presented for participants in the mITT Population who had Baseline and on-treatment phenotypic resistance testing. The outcome was originally designed to be assessed up to 96 weeks of treatment, but it was analyzed up to Week 24 as the study was terminated early.
Week 24
Change From Baseline in Logarithm to the Base 10 (log10) HIV-1 RNA Over Time
大体时间：Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
Blood samples were collected for analysis of HIV-1 RNA. Values obtained at Day 1 were considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Change from Baseline in plasma HIV-1 RNA (log10) is summarized over time for the mITT Population using observed values, which excluded participants without HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (10 October 2016). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.
Baseline (Day 1) and Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
Change From Baseline in Cluster of Differentiation (CD)4+ Thymus (T)-Cell Counts Over Time
大体时间：Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
CD4+ T-cell counts was assessed using flow cytometry. Values obtained at Day 1 were considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Change from Baseline in CD4+T- cell counts is summarized over time for the mITT Population using observed values, which excluded participants without HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (10 October 2016). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.
Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
Change From Baseline in the Percentage of CD4+ T-cells Over Time
大体时间：Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
CD4+ T-cell counts overall was assessed using flow cytometry. Values obtained at Day 1 were considered as Baseline value. Change from Baseline was calculated as value at indicated time point minus Baseline value. Change from Baseline in percentage of CD4+T- cell counts is summarized over time for the mITT Population using observed values, which excluded participants without HIV-1 RNA result data in the assessment visit windows due to discontinuation and who discontinued on or after the date of site notification of study termination by the sponsor (10 October 2016). Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). NA indicates standard deviation could not be calculated as only one participant was analyzed at the specified time point.
Baseline (Day 1) and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72 and 84
Number of Participants With Serious Adverse Events (SAEs) and Adverse Events Leading to Discontinuation (AELD)
大体时间：Up to Week 96
Any untoward medical occurrence that at any dose: results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention were categorized as SAE. Number of participants with SAEs and AELDs is summarized.
Up to Week 96
Number of Participants With at Least One Centers for Disease Control (CDC) Class C Events
大体时间：Up to Week 96
The occurrence of new AIDS defining events that is CDC class C events is presented.
Up to Week 96
Maximum Observed Plasma Concentration (Cmax), Observed Pre-dose Plasma Concentration (C0) and Observed Plasma Concentration at the End of a Dosing Interval (Ctau) of BMS-955176/GSK3532795
大体时间：Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Serial blood samples were collected at indicated time points for intensive pharmacokinetic (PK) assessment. The PK assessments were performed on evaluable PK Population, a sub-population which included all treated participants who had adequate PK profiles.
Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Time of Maximum Observed Plasma Concentration (Tmax) of BMS-955176/GSK3532795
大体时间：Pre-dose (morning) and 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Serial blood samples were collected at indicated time points for intensive PK assessment.
Pre-dose (morning) and 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Area Under the Concentration-time Curve in One Dosing Interval (AUC [Tau]) of BMS-955176/GSK3532795
大体时间：Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)
Serial blood samples were collected at indicated time points for intensive PK assessment.
Pre-dose (morning) and at 0.5, 1, 1.5, 2, 4, 4.5, 5, 6, 8, 12 (evening pre-dose) and 24 hours (morning pre-dose) at Week 2 (Days 12 to 16)

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

ViiV Healthcare

合作者

GlaxoSmithKline

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

有用的网址

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 (实际的)

2015年5月12日

初级完成 (实际的)

2016年5月26日

研究完成 (实际的)

2017年8月21日

研究注册日期

首次提交

2015年3月11日

首先提交符合 QC 标准的

2015年4月9日

首次发布 (估计)

2015年4月14日

研究记录更新

最后更新发布 (实际的)

2018年9月19日

上次提交的符合 QC 标准的更新

2018年8月20日

最后验证

2018年8月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • 205891
  • 2013-005487-26 (EudraCT编号)
  • AI468-038 (其他标识符：Bristol-Myers Squibb)

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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