A Phase IIb, Randomized, Double-blind, Parallel-group Study to Assess the Efficacy, Safety, Tolerability, and Resistance Profile of GSK3640254 in Combination With Dolutegravir Compared to Dolutegravir Plus Lamivudine in HIV-1 Infected, Treatment-naïve Adults
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 85
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24
研究概览
简要总结
The purpose of this study was to evaluate the efficacy of GSK3640254 + DTG relative to lamivudine (3TC) + DTG in treatment-naïve adult participants living with human immunodeficiency virus (HIV)-1. The participants were randomized to one of the three doses of blinded GSK3640254 (100, 150, or 200 milligrams [mgs]) or a reference arm of blinded 3TC-each in combination with open label DTG.
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
- Double (Participant, Investigator)
盲法说明
The dose level of GSK3640254 in each of the treatment arms containing GSK3640254 was blinded to the research participants and all study personnel during the study through the Week 24 primary endpoint.
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
- •Treatment-naive, defined as no anti-retrovirals (ARVs) (in combination or monotherapy) received after a known diagnosis of HIV-1 infection.
- •Documented HIV infection and Screening plasma HIV-1 RNA greater than or equal to (>=)1000 c/mL.
- •Screening CD4+ T-cell count >=250 cells per millimeter^3 (cells/cubic millimeter).
- •Body weight >=50.0 kilograms (kg) (110 pounds [lbs.]) for men and >=45.0 kg (99 lbs.) for women and body mass index (BMI) >18.5 kilograms per meter^2 (kg/meter square). Calculations will utilize sex assigned at birth.
排除标准
- •Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease [CDC, 2014], except cutaneous Kaposi's sarcoma not requiring systemic therapy.
- •Presence of primary HIV infection, evidenced by acute retroviral syndrome (example [e.g.], fever, malaise, fatigue, etc.) and/or evidence of recent (within 3 months) documented viremia without antibody production and/or evidence of recent (within 3 months) documented seroconversion.
- •Unstable liver disease (as defined by any of the following: presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice or cirrhosis), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic liver disease per investigator assessment);
- •History of ongoing or clinically relevant hepatitis within the previous 6 months.
- •Any history of significant underlying psychiatric disorder.
- •Any history of major depressive disorder with or without suicidal features, or anxiety disorders, that required medical intervention (pharmacologic or not) such as hospitalization or other inpatient treatment and/or chronic (>6 months) outpatient treatment.
- •A pre-existing condition, in the opinion of the Investigator or Medical Monitor, that could interfere with normal gastrointestinal anatomy or motility (e.g., gastroesophageal reflux disease [GERD], gastric ulcers, gastritis, inflammatory bowel disease), hepatic and/or renal function, or with the absorption, metabolism, and/or excretion of the study interventions or render the participant unable to take oral study treatment.
- •Familial or personal history of long QT syndrome or sudden cardiac death.
- •Active treatment for a viral infection other than HIV-1, such as Hepatitis B, with an agent that is active against HIV-1 (were known to be infected with HIV-1 after treatment for Hepatitis B was completed).
- •Participants who require concomitant medications known to be associated with a prolonged corrected QT (QTc) interval.
- •Exposure to an experimental drug, human blood product, monoclonal antibody, or vaccine (which does not have emergency, conditional, or standard market authorization) within 28 days prior to the first dose of study treatment.
研究组 & 干预措施
GSK3640254 100 mg + Dolutegravir (DTG) 50 mg
Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.
干预措施: GSK3640254 (Drug)
GSK3640254 100 mg + Dolutegravir (DTG) 50 mg
Participants with human immunodeficiency virus type 1 (HIV-1) orally received low dose (100 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.
干预措施: Dolutegravir (Drug)
GSK3640254 150 mg + DTG 50 mg
Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.
干预措施: GSK3640254 (Drug)
GSK3640254 150 mg + DTG 50 mg
Participants with HIV-1 orally received medium dose (150 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.
干预措施: Dolutegravir (Drug)
GSK3640254 200 mg + DTG 50 mg
Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.
干预措施: GSK3640254 (Drug)
GSK3640254 200 mg + DTG 50 mg
Participants with HIV-1 orally received high dose (200 mg) GSK3640254 tablet blinded and 50 mg DTG unblinded. Each participant received one tablet per day of each intervention up to Week 24.
干预措施: Dolutegravir (Drug)
DTG 50 mg + Lamivudine (3TC) 300 mg
Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC. Each participant received one capsule per day of each intervention up to Week 24.
干预措施: Dolutegravir (Drug)
DTG 50 mg + Lamivudine (3TC) 300 mg
Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC. Each participant received one capsule per day of each intervention up to Week 24.
干预措施: Lamivudine capsules (Drug)
DTG 50 mg + Lamivudine (3TC) 300 mg
Participants with HIV-1 orally received unblinded 50 mg DTG one tablet and blinded 300 mg 3TC. Each participant received one capsule per day of each intervention up to Week 24.
干预措施: Lamivudine tablets (Drug)
结局指标
主要结局
Percentage of Participants With Plasma HIV-1 Ribonucleic Acid (RNA) Less Than (<)50 Copies Per Milliliter (c/mL) at Week 24
时间窗: At Week 24
Percentage of participants with plasma HIV-1 RNA \<50 c/mL at Week 24 using the Food and Drug Administration (FDA) snapshot algorithm was assessed to evaluate the antiviral activity in HIV-1 infected ART (anti-retroviral therapy)-naïve participants.
次要结局
- Change From Baseline in HIV-1 RNA Through Week 24(At Week 24 compared to baseline (Day 1))
- Absolute Values of Cluster of Differentiation 4+ (CD4+) T-cell Counts Through Week 24(At Baseline (Day 1) and Week 24)
- Change From Baseline in CD4+ T-cell Counts Through Week 24(At Week 24 compared to baseline (Day 1))
- Number of Participants With Serious Adverse Events (SAEs) and Deaths, up to End of Continued Access to Treatment Post-study Termination (Day 478)(From Day 1 up to end of continued access to treatment post-study termination (Day 478))
- Absolute Values of HIV-1 RNA Through Week 24(At Baseline (Day 1) and Week 24)
- Number of Participants With Adverse Events (AEs) Leading to Discontinuation, up to End of Continued Access to Treatment Post-study Termination (Day 478)(From Day 1 up to end of continued access to treatment post-study termination (Day 478))
- Number of Participants With Adverse Events of Special Interest (AESIs), up to End of Continued Access to Treatment Post-study Termination (Day 478)(From Day 1 up to end of continued access to treatment post-study termination (Day 478))
- Number of Participants Who Develop Genotypic Resistance up to Week 24(From Day 1 up to Week 24)
- Number of Participants Who Develop Phenotypic Resistance up to Week 24(From Day 1 up to Week 24)
- Trough Concentration (Ctrough) of GSK3640254 at Weeks 2, 4, 8, 12 and 24(At Weeks 2, 4, 8, 12 (PRE DOSE), 12 (2-6HR POST DOSE), 24 (PRE DOSE), 24 (2-6HR POST DOSE))