A Randomized, Double-Blind Study of the Safety and Efficacy of GSK1349572 Plus Abacavir/Lamivudine Fixed-Dose Combination Therapy Administered Once Daily Compared to Atripla 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
- 844
- 试验地点
- 1
- 主要终点
- Proportion of Subjects Responding Based on Plasma HIV-1 RNA <50 c/mL at 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 plus Abacavir/Lamivudine once daily versus Efavirenz/Emtricitabine/Tenofovir disoproxil fumarate (ATRIPLA® a trade mark of Bristol-Myers Squibb and Gilead Sciences LLC) over 48 weeks; non-inferiority will also be tested at Week 96. This study will be conducted in HIV-1 infected ART-naïve adult subjects. Long term antiviral activity, tolerability, safety, and development of viral resistance will be evaluated.
详细描述
ING114467 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 plus abacavir/lamivudine fixed-dose combination once daily (approximately 394 subjects)
OR
Atripla once daily (approximately 394 subjects)
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 plus abacavir/lamivudine fixed-dose combination through the study until it is locally available-as long as they continue to derive clinical benefit, until they meet a protocol-defined reason for discontinuation, or until development of the compound is terminated.
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
- •A negative HLAB*5701 allele assessment
排除标准
- •Women who are pregnant or breastfeeding;
- •Active Center for Disease and Prevention Control (CDC) Category C disease
- •Hepatic impairment
- •HBV co-infection
- •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
Dolutegravir (N=~394):
Dolutegravir 50mg once daily + abacavir/lamivudine as the fixed-dose combination once daily + Atripla placebo once daily
干预措施: Dolutegravir (Drug)
Dolutegravir (N=~394):
Dolutegravir 50mg once daily + abacavir/lamivudine as the fixed-dose combination once daily + Atripla placebo once daily
干预措施: Abacavir/Lamivudine (Drug)
Dolutegravir (N=~394):
Dolutegravir 50mg once daily + abacavir/lamivudine as the fixed-dose combination once daily + Atripla placebo once daily
干预措施: Atripla placebo (Drug)
Atripla (N=~394):
Atripla once daily + Dolutegravir placebo once daily + abacavir/lamivudine as the fixed-dose combination placebo once daily
干预措施: Atripla (Drug)
Atripla (N=~394):
Atripla once daily + Dolutegravir placebo once daily + abacavir/lamivudine as the fixed-dose combination placebo once daily
干预措施: Abacavir/Lamivudine Placebo (Drug)
Atripla (N=~394):
Atripla once daily + Dolutegravir placebo once daily + abacavir/lamivudine as the fixed-dose combination placebo once daily
干预措施: Dolutegravir placebo (Drug)
结局指标
主要结局
Proportion of Subjects Responding Based on Plasma HIV-1 RNA <50 c/mL at Week 48
时间窗: Week 48
The percentage of participants with plasma HIV-1 RNA \<50 c/mL at Week 48 was assessed. Plasma samples were collected for the quantitative assessment of HIV-1 RNA based on the Missing, Switch, or Discontinuation equals Failure (MSDF) algorithm,as codified by the Food and Drug Administration's Snapshot algorithm. This algorithm treats all participants without HIV-1 RNA data at the visit of interest (due to missing data or discontinuation of investigationl product prior to the visit window) as non-responders, as well as participants who switched their concomitant antiretroviral therapy (ART) in certain scenarios. Since changes in ART were not permitted in this protocol, all such participants who changed ART were to be considered non-responders. Otherwise, virologic success or failure was to be determined by the last available HIV-1 RNA assessment while the participant was on treatment within the visit of interest window.
次要结局
- Percentage of Participants With Plasma Human Immunodeficiency Virus -1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/Milliliter (c/mL) at Week 96 and Week 144(Week 96 and Week 144)
- Number of Participants With a Confirmed Plasma HIV-1 RNA Level >=1000 c/mL at or After Week 16 and Before Week 24, or a Confirmed Plasma HIV-1 RNA Level >=200 c/mL at or After Week 24(From Baseline until Week 144) (average of 877.4 days for DTG; average of 788.8 study days for EFV/TDF/FTC))
- Change From Baseline in CD4+ Cell Counts at Week 144(Baseline and Week 144)
- Number of Participants With the Indicated Grade 1 to 4 Clinical and Hematology Toxicities at Week144(From Baseline until Week 144)
- Time to Viral Suppression (<50 c/mL)(From Baseline until Week 144) (average of 877.4 days for DTG; average of 788.8 study days for EFV/TDF/FTC))
- Change From Baseline in Plasma HIV-1 RNA at Weeks 2, 4, 8, 12, 16, 24, 32, 40,48, 60, 72, 84, 96, 108, 120, 132 and 144(Baseline and at Weeks 2, 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144)
- Number of Participants With the Indicated Post-baseline HIV-associated Conditions and Progression, Excluding Recurrences at Week 144(From Baseline until Week 144)
- Change From Baseline in CD4+ Cell Counts at Weeks 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144(Baseline and Week 4, 8, 12, 16, 24, 32, 40, 48, 60, 72, 84, 96, 108, 120, 132 and 144)
- Number of Participants With the Indicated Genotypic Resistance With Virological Failure (VF) Through 144(Through Week 144)
- Change From Baseline in the Symptom Bother Score (SBS) at Week 4 Through Week 48(Baseline and Week 4 through 48)