Efficacy of Dolutegravir Plus Lamivudine Compared to Dolutegravir Plus Tenofovir/Emtricitabine in HIV-1-infected Treatment-naïve Adults Without Baseline Genotyping Test (D2ARLING Study)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 244
- 试验地点
- 1
- 主要终点
- Virologic Efficacy
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of DTG + 3TC versus DTG + TDF/FTC over 48 weeks in HIV-1 naive patients in a real life setting with no baseline HIV genotypic resistance testing available.
详细描述
This is a 48-week, Phase IV, randomized, open-label, to assess the non-inferior antiviral activity (VL < 50 c/ml) of 2DR DTG+3TC versus 3DR TDF/FTC + DTG over 48 weeks in HIV1 naïve adult patients without baseline GT available at Day 1 visit. Subjects will be stratified by screening HIV-1 RNA (≤100,000 c/mL or >100,000 c/mL) and Screening CD4+ cell count (≤ or >200 cells/mm3).
The study will comprise:
- a 28-day Screening Phase (which may be extended to 35 days to allow receipt of all Screening assessment results).
- an Open-label Randomized Phase (Day 1 to Week 48).
Approximately 200 HIV-1 naïve adult patients will be randomized 1:1 to receive 2DR DTG+3TC versus 3DR TDF/FTC + DTG for 48 weeks.
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
- None
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
- •Subject should be antiretroviral naïve (defined as <=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV 1 infection).
- •Age ≥ 18 years
- •Screening plasma HIV-1 RNA ≥1000 c/mL
- •CD4 cell count nadir: any value
- •Effective contraception for women of childbearing potential.
- •Informed consent form signed by patient and investigator
排除标准
- •History of suicide ideation, intention or action.
- •Evidence of HBV infection based on the results of testing at Screening* for HBV surface antigen (HBsAg), HBV core antibody (anti-HBc), HBV surface antibody (antiHBs or HBsAb), and HBV DNA as follows: Subjects positive for HBsAg are excluded; Subjects negative for anti-HBs and HBsAg but positive for anti-HBc and positive for HBV DNA are excluded.
- •Anticipated need for any HCV therapy during the first 48 weeks of the study.
- •Acute symptomatic HIV Infection.
- •Any active Opportunistic Infection (category C, CDC 2014).
- •Current pregnancy or breastfeeding.
- •No effective contraception for the women of childbearing.
- •Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening period to verify a result.
- •ALT (Alanine Aminotransferase) ≥ 5 x upper limit of normal value (ULN) or AST (Aspartate Aminotransferase) ≥ 3 x ULN and bilirubinemia ≥ 1.5 x ULN (with 35% direct bilirubinemia).
- •Unstable liver disease (ascitis, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice).
- •Creatinine clearance of <50 mL/min/1.73 m2 (Cockroft-Gault method).
- •History or presence of allergy to the trial drugs or their components.
- •Severe hepatic insufficiency (Child Pugh Class C).
- •Any available historical resistance test result.
研究组 & 干预措施
Dolutegravir + lamivudine
Dolutegravir 50 mg, 1 tablet QD plus lamivudine 300 mg, 1 tablet QD
干预措施: Lamivudine 300 MG (Drug)
Dolutegravir + emtricitabine/tenofovir (FTC/TDF)
Dolutegravir 50 mg, 1 tablet QD plus FTC/TDF 200/300 mg, 1 coformulated tablet QD
干预措施: Emtricitabine / Tenofovir Disoproxil Pill (Drug)
结局指标
主要结局
Virologic Efficacy
时间窗: 48 weeks
To demonstrate the non-inferior antiviral activity (VL \< 50 c/ml) of 2DR DTG+3TC versus 3DR TDF/FTC + DTG over 48 weeks in HIV-1 naïve adult patients without baseline genotypic resistance testing available. Endpoint: Proportion of subjects with plasma HIV-1 RNA \<50 copies/mL (c/mL) at Week 48 using the FDA Snapshot algorithm \[Missing, Switch or Discontinuation = Failure (MSD=F)\] for the intent-to-treat exposed (ITT-E) population.
次要结局
- Genetic barrier(48 weeks)
- Efficacy in presence of any major resistanceassociated mutation al baseline(48 weeks)