A Randomized, Double-Blind (Sponsor-Unblinded), Placebo-Controlled, Adaptive Study to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of VH3739937 in Treatment-Naïve Adults Living With HIV-1
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 21
- 试验地点
- 1
- 主要终点
- Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA).
研究概览
简要总结
The primary purpose of this study is to assess the antiviral activity of VH3739937 in Human Immunodeficiency Virus Type-1 (HIV-1) infected treatment naive (TN) participants during monotherapy.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants who are overtly healthy (other than HIV infection) as determined by the Investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring
- •Positive HIV antibody test
- •Treatment-naïve: No Antiretrovirals (ARVs) (in combination or monotherapy) received after the diagnosis of HIV-1 infection
- •Body weight ≥50.0 kilogram (kg) (110 pounds [lbs]) for men and ≥45.0 kg (99 lbs) for women and BMI for all participants within the range 18.5-35.0 kilogram per meter square (kg/m^2).
- •Capable of giving signed informed consent
- •Participant must be willing and able to start Combination Antiretrovial Therapy (cART) as selected with the Investigator on Study Day 8 (except in the case of early termination, clinically relevant AE/SAE, lab abnormality, the withdrawal of consent, lost to follow-up, etc., where circumstances could dictate otherwise).
排除标准
- •Current or chronic history of liver disease or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
- •Participants with primary HIV infection, evidenced by acute retroviral syndrome (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
- •Myocardial infarction, acute coronary syndrome, unstable angina, stroke, transient ischemic attack, or intermittent claudication in the past 3 months
- •The participant has received an investigational HIV vaccine (immunotherapeutic or immunomodulatory)
- •Regular use of drugs of abuse
- •Sensitivity to heparin or heparin-induced thrombocytopenia
研究组 & 干预措施
VH3739937 Low Dose Group
Participants received a low dose of VH3739937 as loading Dose 1 (LD1) on Day 1, followed by a once-daily (QD) dose of VH3739937 as maintenance Dose 1 (MD1) from Days 2 through 7, where MD1 was lower than LD1. On Day 8, all participants transitioned to standard-of-care (SOC) combination antiretroviral therapy (cART) and continued study assessments through Day 25.
干预措施: VH3739937 (Drug)
VH3739937 Medium Dose Group
Participants received a medium dose of VH3739937 as loading Dose 2 (LD2) on Day 1, followed by a QD dose of VH3739937 as maintenance Dose 2 (MD2) from Days 2 through 7, where MD2 was lower than LD2. On Day 8, all participants transitioned to SOC cART and continued study assessments through Day 25.
干预措施: VH3739937 (Drug)
VH3739937 High Dose Group
Participants received a single high dose (Dose 3) of VH3739937 on Day 1. On Day 8, all participants transitioned to SOC cART and continued study assessments through Day 25.
干预措施: VH3739937 (Drug)
Placebo once daily (QD)
Participants received Placebo QD from Day 1 through Day 7. On Day 8, all participants transitioned to SOC cART and continued study assessments through Day 25.
干预措施: Placebo (Drug)
Placebo single dose (SD)
Participants received Placebo SD on Day 1. On Day 8, all participants transitioned to SOC cART and continued study assessments through Day 25.
干预措施: Placebo (Drug)
结局指标
主要结局
Maximum Change From Baseline in Plasma Human Immunodeficiency Virus-1 (HIV-1) Ribonucleic Acid (RNA).
时间窗: From Day 1 to Day 8
Plasma samples were collected for the quantitative analysis of plasma HIV-1 RNA. The maximum change from baseline was calculated by determining the largest change from baseline value across all assessment timepoints. This is identified by subtracting the lowest post-dose visit value up to Day 8 (inclusive) from the baseline value. The baseline was defined as the most recent pre-dose assessment with a valid, non-missing value, including measurements from any unscheduled visits.
次要结局
- Number of Participants With Serious Adverse Events (SAEs) During Study Intervention Period(From Day 1 to Day 8)
- Number of Reported Deaths(From Day 1 to Day 8)
- Number of Participants With Adverse Events (AEs) Leading to Discontinuation(From Day 1 to Day 8)
- Maximum Observed Plasma Concentration (Cmax) of VH3739937 on QD Dosing(Pre-dose, 1 hour (h), 2 h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h post-dose on Day 1)
- Concentration at 24 Hours (C24) Post Dose of VH3739937 on QD Dosing(At 24h post-dose on Day 1)
- Cmax Post Single Dose of VH3739937(Pre-dose, 1 hour (h), 2 h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h post-dose (single dose administered on Day 1))
- Tmax Post Single Dose of VH3739937(Pre-dose, 1 hour (h), 2 h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h post-dose (single dose administered on Day 1))
- Concentration at 168 Hours (C168) Post Single Dose of VH3739937(At 168 hours post-dose (single dose administered on Day 1))
- Area Under the Concentration-time Curve From Zero to 168h [AUC(0-168)] Post Single Dose of VH3739937(Pre-dose, 1 hour (h), 2 h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h, 48h, 72h, 96h, 120h, 144h, 168h post-dose (single dose administered on Day 1))
- Time to Maximum Concentration (Tmax) of VH3739937 on QD Dosing(Pre-dose, 1 hour (h), 2 h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h post-dose on Day 1)
- Area Under the Concentration-time Curve From Zero to 24h (AUC[0-24]) of VH3739937 on QD Dosing.(Pre-dose, 1 hour (h), 2 h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h post-dose on Day 1)
- Cmax of VH3739937 at Steady State (Cmax, ss) on QD Dosing(Pre-dose, 1 hour (h), 2 h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h post-dose on Day 7)
- Tmax of VH3739937 at Steady State (Tmax, ss) on QD Dosing(Pre-dose, 1 hour (h), 2 h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h post-dose on Day 7)
- C24 of VH3739937 at Steady State (C24, ss) on QD Dosing(At 24h post-dose on Day 7)
- AUC(0-24) of VH3739937 at Steady State (AUC[0-24], ss) on QD Dosing(Pre-dose, 1 hour (h), 2 h, 4h, 5h, 6h, 7h, 8h, 9h, 10h, 12h, 24h post-dose on Day 7)