A Randomized, Double-Blind (Sponsor Unblinded), Placebo-Controlled, Phase 2a Trial to Investigate the Antiviral Effect, Safety, Tolerability and Pharmacokinetics of Orally Administered Investigational Capsid Inhibitor Monotherapy in HIV-1 Infected Treatment-Naïve Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 43
- 试验地点
- 1
- 主要终点
- Monotherapy, VH4011499: Maximum Change From Baseline (Day 1) in Plasma HIV-1 RNA log10
研究概览
简要总结
The primary purpose of the study is to evaluate the antiviral activity of orally administered VH4004280 and VH4011499 monotherapy over 10 days in human immunodeficiency virus (HIV-1) infected Treatment-Naïve (TN) participants.
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)
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-1 infection).
- •Screening cluster of differentiation-4 (CD4+) T-cell count greater than or equal to (≥)200 cells/microliter (µL).
- •Documented HIV-1 infection and Screening plasma HIV-1 RNA ≥3000 copies/milliliter (mL).
- •Treatment-naïve: Defined as no antiretroviral therapy received after the diagnosis of HIV-1 infection. Prior use of oral pre-exposure prophylaxis (PreP) is permitted. Prior use of parenteral PreP is exclusionary.
- •Has body mass index (BMI) within the range of 18.5-31.0 kilograms per meter square (kg/m^2).
- •Participants male at birth must use male condoms and participants female at birth who are of childbearing potential must be using acceptable forms of birth control.
- •Participants capable of giving signed informed consent.
- •Participant must be willing and able to start locally accessible and commercially available combination antiretroviral therapy after the monotherapy period.
排除标准
- •Women who are breastfeeding or plan to become pregnant or breast feed during the study.
- •Participants with acute HIV infection.
- •Any evidence of an active Centers for Disease Control and Prevention (CDC) Stage 3 disease.
- •Untreated syphilis infection.
- •Ongoing malignancy other than certain localised malignancies.
- •Treatment with immunomodulating agents or any agent with known anti-HIV activity.
- •Has exclusionary psychiatric, hepatic, cardiovascular gastrointestinal, renal condition.
- •Participant having any condition which, in the opinion of the investigator, may interfere with the absorption, distribution, metabolism or excretion of the study drugs or render the participant unable to take oral medication.
- •Participants having exclusionary electrocardiogram (ECG) findings.
- •Participants who have been exposed to any prohibited medication or vaccine.
- •Participant positive for hepatitis B or hepatitis C.
- •Participants with exclusionary safety laboratory (e.g Grade 3 or greater abnormality).
- •Participants who have positive results for illicit drug use, regular use of drugs of abuse and/or excessive alcohol use.
研究组 & 干预措施
Matching placebo for VH4004280
Participants received a matching placebo for VH4004280 on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: VH4004280 Matching Placebo (Drug)
Part 1a: VH4004280 Dose Level 1
Participants received a single dose of VH4004280 Dose Level 1 (low concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label antiretroviral therapy (ART) up to day 39.
干预措施: VH4004280 (Drug)
Part 1a: VH4004280 Dose Level 1
Participants received a single dose of VH4004280 Dose Level 1 (low concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label antiretroviral therapy (ART) up to day 39.
干预措施: Antiretroviral therapy (Drug)
Part 1a: VH4004280 Dose Level 2
Participants received a single dose of VH4004280 Dose Level 2 (medium concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: VH4004280 (Drug)
Part 1a: VH4004280 Dose Level 2
Participants received a single dose of VH4004280 Dose Level 2 (medium concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: Antiretroviral therapy (Drug)
Part 2a: VH4004280 pre-specified dose
Participants received a single pre-specified dose of VH4004280 (high concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: VH4004280 (Drug)
Part 2a: VH4004280 pre-specified dose
Participants received a single pre-specified dose of VH4004280 (high concentration) on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: Antiretroviral therapy (Drug)
Matching placebo for VH4004280
Participants received a matching placebo for VH4004280 on Day 1 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: Antiretroviral therapy (Drug)
Part 1b: VH4011499 Dose Level 1
Participants received a single dose of VH4011499 Dose Level 1 (low concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants had the option to switch to an open-label ART up to day 39.
干预措施: VH4011499 (Drug)
Part 1b: VH4011499 Dose Level 1
Participants received a single dose of VH4011499 Dose Level 1 (low concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants had the option to switch to an open-label ART up to day 39.
干预措施: Antiretroviral therapy (Drug)
Part 1b: VH4011499 Dose Level 2
Participants received a single dose of VH4011499 Dose Level 2 (medium concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: VH4011499 (Drug)
Part 1b: VH4011499 Dose Level 2
Participants received a single dose of VH4011499 Dose Level 2 (medium concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: VH4011499 Matching Placebo (Drug)
Part 1b: VH4011499 Dose Level 2
Participants received a single dose of VH4011499 Dose Level 2 (medium concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: Antiretroviral therapy (Drug)
Part 2b: VH4011499 pre-specified dose
Participants received a single pre-specified dose of VH4011499 (high concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: VH4011499 (Drug)
Part 2b: VH4011499 pre-specified dose
Participants received a single pre-specified dose of VH4011499 (high concentration) on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: Antiretroviral therapy (Drug)
Matching placebo for VH4011499
Participants received a matching placebo for VH4011499 on Day 1 and Day 6 (evaluated for a 10-day period). On Day 11, participants switched to an open-label ART up to day 39.
干预措施: Antiretroviral therapy (Drug)
结局指标
主要结局
Monotherapy, VH4011499: Maximum Change From Baseline (Day 1) in Plasma HIV-1 RNA log10
时间窗: From Baseline (Day 1) and up to Day 11
Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. Maximum change from baseline was calculated by subtracting the baseline value from the post-dose visit value when the plasma HIV-1 RNA reached its minimum level up to Day 11 (inclusive). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Monotherapy, VH4004280: Maximum Change From Baseline (Day 1) in Plasma HIV-1 Ribonucleic Acid (RNA) log10
时间窗: From Baseline (Day 1) and up to Day 11
Plasma samples were collected for quantitative analysis of plasma HIV-1 RNA. Maximum change from baseline was calculated by subtracting the baseline value from the post-dose visit value when the plasma HIV-1 RNA reached its minimum level up to Day 11 (inclusive). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. The results were expressed as log10 copies per milliliter (log10 c/mL).
次要结局
- Monotherapy: Number of Participants With Any Adverse Events (AEs)(From Baseline (Day 1) and up to Day 11)
- Follow-up: Number of Participants With Any AEs(From Day 11 and up to Day 39)
- Monotherapy: Number of Participants With AEs by Severity(From Baseline (Day 1) and up to Day 11)
- Follow-up: Number of Participants With AEs by Severity(From Day 11 and up to Day 39)
- Monotherapy: Number of Participants With AEs Leading to Study Treatment Discontinuation(From Baseline (Day 1) and up to Day 11)
- Monotherapy and Follow-up, VH4004280: Change From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin(At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39)
- Monotherapy and Follow-up, VH4011499: Change From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin(At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39)
- Monotherapy and Follow-up, VH4004280: Change From Baseline for Liver Panel Laboratory Parameters - Alanine Aminotransferace (ALT), Alkaline Phosphatase (ALP) and Aspartate Aminotransferase (AST)(At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39)
- Monotherapy and Follow-up, VH4011499: Change From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST(At Baseline (Day 1) and at Days 2, 4, 6, 7, 9, 11, 18, 25, 32 and 39)
- Monotherapy and Follow-up, VH4004280: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin(From Baseline (Day 1) and up to Day 39)
- Monotherapy and Follow-up, VH4011499: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - Total Bilirubin and Direct Bilirubin(From Baseline (Day 1) and up to Day 39)
- Monotherapy and Follow-up, VH4004280: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST(From Baseline (Day 1) and up to Day 39)
- Monotherapy and Follow-up, VH4011499: Number of Participants With Maximum Toxicity Grade Increase From Baseline for Liver Panel Laboratory Parameters - ALT, ALP and AST(From Baseline (Day 1) and up to Day 39)
- Monotherapy, VH4004280: Maximum Observed Plasma Drug Concentration (Cmax)(After dose administration at Day 1)
- Monotherapy, VH4011499: Cmax(After dose administration at Day 1 and Day 6)
- Monotherapy, VH4004280: Time to Maximum Observed Plasma Drug Concentration (Tmax)(After dose administration at Day 1)
- Monotherapy, VH4011499: Tmax(After dose administration at Day 1 and Day 6)
- Monotherapy, VH4004280: Plasma Concentration at Day 11 (C11)(At Day 11)
- Monotherapy, VH4011499: C11(At Day 11)
- Monotherapy, VH4004280: Change in Plasma HIV-1 RNA From Baseline(At Baseline (Day 1) and Day 11)
- Monotherapy, VH4011499: Change in Plasma HIV-1 RNA From Baseline(At Baseline (Day 1) and Day 11)