A Phase 2 Clinical Study to Evaluate the Pharmacokinetics, Safety, and Efficacy of Doravirine/Islatravir in Pediatric Participants With HIV-1 Infection Who Are Virologically Suppressed or Treatment-Naïve, Are Less Than 18 Years of Age, and Weigh Greater Than or Equal to 35 kg
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 17
- 主要终点
- Maximum Plasma Concentration (Cmax) of ISL
研究概览
简要总结
This is a phase 2, single-group, multi-site, open-label study of an islatravir/doravirine (ISL/DOR, MK-8591A) fixed dose combination (FDC) for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in pediatric participants who are virologically suppressed (VS) on antiretroviral therapy (ART) for ≥3 months or are treatment-naive (TN). The primary purposes of the study are 1) to examine the steady-state pharmacokinetics (PK) of ISL in plasma; 2) the steady-state PK of ISL-triphosphate (ISL-TP) in peripheral blood mononuclear cells (PBMCs); and 3) to examine the safety and tolerability of ISL/DOR.
详细描述
As of protocol amendment 03 (approved 08-Feb-2022), all participants have been discontinued from study therapy and will be switched to non-study antiretroviral therapy and monitored for safety. The present results cover data obtained through the cut-off date of 30-Mar-2022, and will be updated once monitoring is completed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is HIV-1 positive, is <18 years of age, and weighs ≥35 kg at screening.
- •VS Participants: Is HIV-1 positive at Screening with plasma HIV-1 RNA <50 copies/mL and has been receiving continuous, stable oral 2-drug or 3-drug combination ART ± PK booster with documented viral suppression for ≥3 months prior to providing documented informed consent/assent and has no history of prior virologic treatment failure on any past or current regimen.
- •TN Participants: Is HIV-1 positive at Screening with plasma HIV-1 RNA ≥500 copies/mL and is naive to ART defined as having received <=10 days of prior therapy with any antiretrovirals following HIV-1 diagnosis other than pre-exposure prophylaxis (PrEP) or potentially exposed person (PEP).
- •If female, is not pregnant or breastfeeding, and is either 1) not a woman of childbearing potential (WOCBP) or 2) is a WOCBP and is using acceptable contraception or is abstinent.
排除标准
- •Has HIV-2 infection.
- •Has hypersensitivity or other contraindication to any of the components of the study drugs as determined by the investigator.
- •Has an active diagnosis of hepatitis due to any cause, including active hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive).
- •Has a history of malignancy ≤5 years prior to providing documented informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma.
- •Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate.
- •Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies from 45 days prior to Day 1 through the study treatment period.
- •Is currently taking long-acting cabotegravir-rilpivirine.
- •Is currently participating in or has participated in an interventional clinical study with an investigational compound or device from 45 days prior to Day 1 through the study treatment period.
- •Has a documented or known virologic resistance to DOR/ISL (DOR resistance substitutions in reverse transcriptase: V106A/M, V108I, Y188L, H221Y, P225H, F227C/L, M230I/L, L234I, P236L, or Y318F; ISL resistance substitution in reverse transcriptase: M184V/I).
- •Has exclusionary laboratory values.
- •Is female and expecting to conceive or donate eggs at any time during the study.
研究组 & 干预措施
DOR/ISL
Pediatric participants with HIV-1 infection receive DOR/ISL for 96 weeks.
干预措施: DOR/ISL (Drug)
结局指标
主要结局
Maximum Plasma Concentration (Cmax) of ISL
时间窗: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28
The Cmax of ISL in plasma was determined at steady state.
C24 of ISL-TP in PBMCs
时间窗: 24 hours post-dose on Day 28
The C24 of ISL-TP in PBMCs was determined at steady state.
Apparent Total Clearance From Plasma (CL/F) of ISL
时间窗: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28
The CL/F of ISL from plasma was determined at steady state.
Apparent Volume of Distribution During Terminal Phase (Vz/F) of ISL
时间窗: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28
The Vz/F of ISL was determined at steady state.
Number of Participants Discontinuing From Study Treatment Due to an AE
时间窗: Up to 24 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
AUC0-last of ISL-triphosphate (ISL-TP) in Peripheral Blood Mononuclear Cells (PBMCs)
时间窗: Pre-dose, and 4 and 24 hours post-dose on Day 28
The AUC0-24 of ISL-TP in PBMCs was determined at steady state.
Area Under the Plasma Drug Concentration-time Curve From 0 to 24 Hours Post-dose (AUC0-24) of Islatravir (ISL)
时间窗: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28
The AUC0-24 of ISL in plasma was determined at steady state.
Time to Reach Maximum Plasma Concentration (Tmax) of ISL
时间窗: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28
The Tmax of ISL in plasma was determined at steady state.
Apparent Plasma Terminal Half-life (t½) of ISL
时间窗: Pre-dose, and 0.5, 1, 2, 4, 8, 12, and 24 hours post-dose on Day 28
The t½ of ISL in plasma was determined at steady state.
Cmax of ISL-TP in PBMCs
时间窗: Pre-dose, and 4, and 24 hours post-dose on Day 28
The Cmax of ISL-TP in PBMCs was determined at steady state.
Number of Participants Experiencing ≥1 Adverse Event (AE)
时间窗: Up to 24 weeks
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
次要结局
- Percentage of Virologically Suppressed (VS) Participants With HIV-1 Ribonucleic Acid (RNA) ≥50 Copies/mL(Week 24)
- Percentage of Treatment Naive (TN) Participants With HIV-1 RNA <50 Copies/mL(Week 24)
- Incidence of Viral Drug Resistance to ISL(Up to 24 weeks)
- Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-cells in VS Participants(Baseline (Day 1) and Week 24)
- Change From Baseline in CD4+ T-cells in TN Participants(Baseline (Day 1) and Week 24)
- Incidence of Viral Drug Resistance to DOR(Up to 24 weeks)
- Palatability of DOR/ISL Tablet(Baseline (Day 1), Week 4, and Week 24)
- Percentage of VS Participants With HIV-1 RNA <50 Copies/mL(Week 24)
- Acceptability of DOR/ISL Tablet(Baseline (Day 1), Week 4, and Week 24)