A Phase 3, Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 643
- 试验地点
- 89
- 主要终点
- Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 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 regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with BIC/FTC/TAF as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48. Participants who benefit from their assigned intervention (as determined by investigator) will be able to continue treatment through a 24-week study extension.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Is HIV-1 positive with plasma Human Immunodeficiency Virus 1 (HIV-1) RNA <50 copies/mL at screening.
- •Has been receiving BIC/FTC/TAF therapy 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.
- •Female is 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 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 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 DOR.
- •Female expects to conceive or donate eggs at any time during the study.
研究组 & 干预措施
DOR/ISL
A fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and placebo to Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) for 96 weeks.
干预措施: DOR/ISL (Drug)
DOR/ISL
A fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and placebo to Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) for 96 weeks.
干预措施: Placebo to BIC/FTC/TAF (Drug)
BIC/FTC/TAF
50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
干预措施: DOR/ISL (Drug)
BIC/FTC/TAF
50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
干预措施: BIC/FTC/TAF (Drug)
BIC/FTC/TAF
50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.
干预措施: Placebo to FDC DOR/ISL (Drug)
结局指标
主要结局
Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 RNA) ≥50 Copies/mL at Week 48
时间窗: Week 48
The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. 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 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an AE up to week 48 is presented.
Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 48
时间窗: Up to 48 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to an AE up to week 48 is presented.
次要结局
- Participants With HIV-1 RNA ≥50 Copies/mL at Week 96(Week 96)
- Change From Baseline in Body Weight at Week 96(Baseline and Week 96)
- Change From Baseline in Cluster of Differentiation-positive (CD4+) T-cell Count at Week 48(Baseline and Week 48)
- Change From Baseline in CD4+ T-cell Count at Week 144(Baseline and Week 144)
- Change From Baseline in Body Weight at Week 48(Baseline and Week 48)
- Change From Baseline in Body Weight at Week 144(Baseline and Week 144)
- Change From Baseline in CD4+ T-cell Count at Week 96(Baseline and Week 96)
- Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48(Week 48)
- Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48(Week 48)
- Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 96(Week 96)
- Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96(Week 96)
- Participants With HIV-1 RNA ≥50 Copies/mL at Week 144(Week 144)
- Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 144(Week 144)
- Participants With Viral Drug Resistance-associated Substitutions at Week 48(Week 48)
- Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 144(Week 144)
- Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 144(Up to Week 144)
- Percentage of Participants With One or More AEs up to Week 144(Up to Week 144)