A Phase 3, Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Antiretroviral Therapy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 553
- 试验地点
- 53
- 主要终点
- Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48
研究概览
简要总结
The primary objectives of this study are to evaluate the safety and tolerability of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued baseline antiretroviral therapy (ART), through Week 48; and to evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued baseline ART at Week 48. The primary hypothesis is that DOR/ISL is non-inferior to continued baseline ART, as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48, with a margin of 4 percentage points used to define non-inferiority.
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-1 (HIV-1) positive with plasma HIV-1 Ribonucleic Acid (RNA) <50 copies/mL at screening
- •Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) antiretroviral therapy ART with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 consecutive months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen
- •Female is not a participant of childbearing potential (POCBP); or if a POCBP uses an acceptable contraceptive method or abstains from penile-vaginal intercourse as their preferred and usual lifestyle; has a negative highly sensitive pregnancy test; and whose medical history, menstrual history, and recent sexual activity has been reviewed by the investigator
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 a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening
- •Has active hepatitis B virus (HBV) infection
- •Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis
- •Has a ≤5 years prior history of malignancy
- •Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers
- •Has taken long-acting HIV therapy at any time
- •Is currently participating in or has participated in a clinical study and received (or is receiving) 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 Doravine (DOR)
研究组 & 干预措施
DOR/ISL
Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) receive doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
干预措施: DOR/ISL (Drug)
ART + DOR/ISL
Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).
干预措施: ART (Drug)
结局指标
主要结局
Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 48
时间窗: Week 48
HIV-1 RNA levels in plasma were measured by polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of \<50 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) at Week 48
时间窗: Up to Week 48
An AE is 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 from Day 1 up to Week 48 are reported.
Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48
时间窗: Up to Week 48
An AE is 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 leading to discontinuation of study intervention from Day 1 up to Week 48 are reported.
次要结局
- Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48(Week 48)
- Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 48(Week 48)
- Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96(Week 96)
- Participants With HIV-1 RNA <200 Copies/mL at Week 144(Week 144)
- Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96(Week 96)
- Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 144(Week 144)
- Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96(Week 96)
- Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144(Week 144)
- Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to Week 48(Baseline at Day 1 and Week 48)
- Mean Change of Plasma CD4+ T-Cell Count From Baseline Week 48 to Week 96(Baseline at Week 48 and Week 96)
- Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 48 to Week 144(Baseline at Week 48 and Week 144)
- Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 96(Baseline at Day 1 and Week 96)
- Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 144(Baseline at Day 1 and Week 144)
- Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48(Up to Week 48)
- Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48(Baseline and Week 48)
- Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48(Baseline and Week 48)
- Participants With One or More AEs at Week 96(Up to Week 96)
- Participants With One or More AEs at Week 144(Up to Week 144)
- Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 96(Up to Week 96)
- Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 144(Up to Week 144)
- Percentage of Participants With One or More AEs From Week 48 up to Week 96(Week 48 up to Week 96)
- Percentage of Participants With One or More AEs From Week 48 up to Week 144(Week 48 up to Week 144)
- Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 96(Week 48 up to Week 96)
- Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 144(Week 48 up to Week 144)