A Randomized, Double Blind Study of the Safety and Efficacy of GSK1349572 50mg Once Daily to Raltegravir 400mg Twice Daily Both Administered With Fixed-dose Dual Nucleoside Reverse Transcriptase Inhibitor Therapy Over 96 Weeks in HIV-1 Infected Antiretroviral Therapy Naive Adult Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 828
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48
研究概览
简要总结
The purpose of this trial is to assess the non-inferior antiviral activity of GSK1349572 50 mg once daily versus RAL 400mg twice daily over 48 weeks; non-inferiority will also be tested at Week 96. Both GSK1349572 and RAL will be given in combination with fixed-dose dual NRTI therapy (ABC/3TC or TDF/FTC). This study will be conducted in HIV-1 infected ART-naïve adult subjects.
详细描述
ING113086 is a Phase 3 randomized, double-blind, double dummy, active-controlled, multicenter, study conducted in approximately 788 HIV-1 infected ART-naïve subjects. Subjects will be randomized 1:1 one of the following treatment arms:
- GSK1349572 50 mg once daily (approximately 394 subjects) + fixed-dose dual NRTI therapy (either ABC/3TC or TDF/FTC)
OR 2. 400 mg RAL twice daily (approximately 394 subjects) + fixed-dose dual NRTI therapy (either ABC/3TC or TDF/FTC)
Analyses will be conducted at 48 weeks and 96 weeks. Subjects randomized to receive GSK1349572 and who successfully complete 96 weeks of treatment will continue to have access to GSK1349572 through the study until either it is locally available, as long as they continue to derive clinical benefit.
ViiV Healthcare is the new sponsor of this study, and GlaxoSmithKline is in the process of updating systems to reflect the change in sponsorship
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Screening plasma HIV-1 RNA ≥1000 c/mL
- •Antiretroviral-naïve (≤ 10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection)
- •Ability to understand and sign a written informed consent form
- •Willingness to use approved methods of contraception to avoid pregnancy (women of child bearing potential only)
- •Age equal to or greater than 18 years
排除标准
- •Women who are pregnant or breastfeeding;
- •Active Center for Disease and Prevention Control (CDC) Category C disease
- •Moderate to severe hepatic impairment
- •Anticipated need for HCV therapy during the study
- •Allergy or intolerance to the study drugs or their components or drugs of their class
- •Malignancy within the past 5 years
- •Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
- •Treatment with radiation therapy, cytotoxic chemotherapeutic agents or any immunomodulator within 28 days of Screening
- •Exposure to an agent with documented activity against HIV-1 in vitro or an experimental vaccine or drug within 28 days of first dose of study medication
- •Primary viral resistance in the Screening result
- •Verified Grade 4 laboratory abnormality
- •ALT >5 xULN
- •ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin);
- •Estimated creatinine clearance <50 mL/min
- •Recent history (≤3 months) of upper or lower gastrointestinal bleed
研究组 & 干预措施
raltegravir (N=~394)
raltegravir 400mg twice daily + GSK1349572 placebo once daily + NRTI background therapy once daily
干预措施: raltegravir Placebo (Other)
GSK1349572 (N=~394)
GSK1349572 50mg once daily + raltegravir placebo twice daily + NRTI background therapy once daily
干预措施: GSK1349572 (dolutegravir) (Drug)
GSK1349572 (N=~394)
GSK1349572 50mg once daily + raltegravir placebo twice daily + NRTI background therapy once daily
干预措施: GSK1349572 Placebo (Other)
GSK1349572 (N=~394)
GSK1349572 50mg once daily + raltegravir placebo twice daily + NRTI background therapy once daily
干预措施: ABC/3TC (Other)
GSK1349572 (N=~394)
GSK1349572 50mg once daily + raltegravir placebo twice daily + NRTI background therapy once daily
干预措施: TDF/FTC (Other)
raltegravir (N=~394)
raltegravir 400mg twice daily + GSK1349572 placebo once daily + NRTI background therapy once daily
干预措施: raltegravir (Drug)
raltegravir (N=~394)
raltegravir 400mg twice daily + GSK1349572 placebo once daily + NRTI background therapy once daily
干预措施: ABC/3TC (Other)
raltegravir (N=~394)
raltegravir 400mg twice daily + GSK1349572 placebo once daily + NRTI background therapy once daily
干预措施: TDF/FTC (Other)
结局指标
主要结局
Percentage of Participants With Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) [HIV-1RNA] <50 Copies (c)/Milliliter (mL) Through Week 48
时间窗: Baseline up to Week 48
Percentage of participants with plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA) with \<50 c/mL was assessed using the Missing, Switch or Discontinuation = Failure (MSDF), as codified by the Food and Drug Administration (FDA) snapshot algorithm. The algorithm treats all participants without HIV-1 RNA data as non-responders, as well as participants who switch their concomitant Antiretroviral Therapy (ART) prior to Week 48 as follows: background ART substitutions not permitted per study; background ART substitutions permitted per study unless the decision to switch was documented as being before or at the first on-treatment visit where HIV-1 RNA was assessed. Otherwise, virologic success or failure will be determined by the last available HIV-1 RNA assessment while the subject was on-treatment. Intent-to-Treat Exposed (ITT-E) Population comprised all randomized participants who received at least one dose of study medication.
次要结局
- Number of Participants With Plasma HIV-1 RNA <50 c/mL(Week 96)
- Change From Baseline in Plasma HIV-1 RNA Over Time(Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96)
- Number of Participants With Detectable HIV-1 Virus That Has Genotypic or Phenotypic Evidence of INI Resistance.(Week 48 and Week 96)
- Absolute Values in Plasma HIV-1 RNA Over Time(Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96)
- Number of Participants With Plasma HIV-1 RNA <400 c/mL(Week 48 and Week 96)
- Change From Baseline in Cluster of Differentiation (CD)4+ Cell Counts Over Time(Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96)
- Absolute Values in CD4+ Cell Counts Over Time(Baseline and Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96)
- Number of Participants With the Indicated Post-Baseline HIV-associated Conditions and Progression, Excluding Recurrences(From Baseline until Week 96)
- Number of Participants With the Indicated Grade 1 to 4 Clinical Chemistry and Hematology Toxicities/Laboratory Adverse Events (AEs)(From Baseline until Week 96)
- Area Under the Plasma Concentration-time Curve From Time Zero to Time Tau [AUC(0-tau)] of DTG(Week 4, Week 24, and Week 48)
- Maximum Plasma Concentration (Cmax) and Concentration at the End of a Dosing Interval (Ctau) of DTG(Week 4, Week 24, and Week 48)