A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 672
- 试验地点
- 134
- 主要终点
- Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 Copies/mL at Week 48
研究概览
简要总结
This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.
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
- •Is human immunodeficiency virus (HIV-1) positive
- •Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen.
- •Females are eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP); is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle; a WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention; if a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
排除标准
- •Has HIV-2 infection
- •Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
- •Has an active diagnosis of hepatitis due to any cause, including active Hepatitis B Virus (HBV) co-infection
- •Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma
- •Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
- •Is currently taking long-acting cabotegravir-rilpivirine
- •Is currently participating in or has participated in a 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 doravirine (DOR)
- •Expects to conceive or donate eggs at any time during the study
研究组 & 干预措施
Group 1: Doravirine/Islatravir (DOR/ISL)
Participants who were previously treated with continuous baseline antiretroviral therapy (ART) will receive DOR/ISL, a fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) orally once daily for 96 weeks.
干预措施: DOR/ISL (Drug)
Group 2: Baseline Antiretroviral Therapy (ART)
Participants received continuous baseline ART for 48 weeks. Continuing participants delayed switch over from baseline ART to DOR/ISL, fixed dose combination of 100 mg DOR/0.75 mg ISL orally once daily, from Week 48 to Week 96, a total DOR/ISL treatment duration of 48 Weeks.
干预措施: DOR/ISL (Drug)
Group 2: Baseline Antiretroviral Therapy (ART)
Participants received continuous baseline ART for 48 weeks. Continuing participants delayed switch over from baseline ART to DOR/ISL, fixed dose combination of 100 mg DOR/0.75 mg ISL orally once daily, from Week 48 to Week 96, a total DOR/ISL treatment duration of 48 Weeks.
干预措施: ART (Drug)
结局指标
主要结局
Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) ≥50 Copies/mL at Week 48
时间窗: Week 48
HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.
Percentage of Participants With One or More Adverse Events (AEs) up to Week 48
时间窗: Up to ~48 Weeks
An AE was defined as 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. The percentage of participants who experienced at least one AE was reported.
Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48
时间窗: Up to ~48 Weeks
An AE was defined as 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. The percentage of participants who discontinued study intervention due to an AE was reported.
次要结局
- Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48(Week 48)
- Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96(Week 96)
- Group 1: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96(Week 96)
- Percentage Change From Baseline in CD4+ T-cell Count at Week 48(Baseline and Week 48)
- Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96(Baseline and Week 96)
- Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96(Week 48 and Week 96)
- Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48(Week 48)
- Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96(Week 96)
- Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)(Baseline and Week 24)
- Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)(Baseline and Week 24)
- Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens(Baseline and Week 24)
- Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)(Baseline and Week 48)
- Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)(Baseline and Week 48)
- Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens(Baseline and Week 48)
- Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens)(Baseline and Week 48)
- Group 1: Percentage of Participants With One or More AEs up to Week 96(Up to ~96 Weeks)
- Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96(Up to ~96 Weeks)
- Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96(Weeks 48-96 (up to ~48 weeks))
- Group 1 & Group 2 (Switch-Over): Percentage of Participants Who Discontinued Study Intervention Due to an AE From Week 48 to Week 96(Weeks 48-96 (up to ~48 weeks))