A Phase 3, Randomized, Active-Controlled, Double-Blind 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 Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 514
- 试验地点
- 49
- 主要终点
- Percentage of Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (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 antiretroviral activity of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) at Week 48; and to evaluate the safety and tolerability of a switch to DOR/ISL compared with continued BIC/FTC/TAF, through Week 48. The primary hypotheses are that (1) DOR/ISL is non-inferior to continued BIC/FTC/TAF, 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; and (2) DOR/ISL is superior to BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 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
- 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 HIV-1 RNA <50 copies/mL
- •Has been receiving BIC/FTC/TAF therapy 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 participant of childbearing potential, not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration
排除标准
- •Has HIV-2 infection
- •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 with laboratory values consistent with cirrhosis
- •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
- •Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers
- •Has a documented or known virologic resistance to DOR
- •Has taken long-acting HIV therapy at any time (e.g., cabotegravir, lenacapavir)
- •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 except those currently enrolled in the comparator arm of an ongoing DOR/ISL study
研究组 & 干预措施
DOR/ISL and Placebo to BIC/FTC/TAF
Participants will receive DOR/ISL 100 mg/0.25 mg and Placebo to BIC/FTC/TAF once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may continue on DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).
干预措施: DOR/ISL (Drug)
DOR/ISL and Placebo to BIC/FTC/TAF
Participants will receive DOR/ISL 100 mg/0.25 mg and Placebo to BIC/FTC/TAF once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may continue on DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).
干预措施: Placebo to BIC/FTC/TAF (Drug)
BIC/FTC/TAF and Placebo to DOR/ISL
Participants will receive BIC/FTC/TAF 50 mg/200 mg/25 mg and Placebo to DOR/ISL once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may switch to DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).
干预措施: BIC/FTC/TAF (Drug)
BIC/FTC/TAF and Placebo to DOR/ISL
Participants will receive BIC/FTC/TAF 50 mg/200 mg/25 mg and Placebo to DOR/ISL once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may switch to DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).
干预措施: Placebo to DOR/ISL (Drug)
结局指标
主要结局
Percentage of Participants With Human Immunodeficiency Virus Type 1 (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 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 Who Experience Adverse Events (AEs) Through Week 48
时间窗: Up to Week 48
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 is reported.
Percentage of Participants Who Discontinue Study Intervention Due to AEs Through Week 48
时间窗: Up to Week 48
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 is 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)
- Change From Baseline in Cluster of Differentiation 4-positive (CD4+) T-cell Count at Week 48(Baseline at Day 1 and Week 48)
- Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48(Up to Week 48)
- Percentage of Participants With HIV-1 RNA ≥50 Copies/mL at Week 96(Week 96)
- Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96(Week 96)
- Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96(Week 96)
- Change From Baseline in CD4+ T-cell Count at Week 96(Baseline at Day 1 and Week 96)
- Number of Participants With Viral Drug Resistance Mutations 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 <200 Copies/mL at Week 144(Week 144)
- Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144(Week 144)
- Change From Baseline in CD4+ T-cell Count at Week 144(Baseline at Day 1 and Week 144)
- Number of Participants With Viral Drug Resistance Mutations at Week 144(Week 144)
- Percentage of Participants Who Experience AEs Through Week 144(Up to Week 144)
- Percentage of Participants Who Discontinue Study Intervention Due to AEs Through Week 144(Up to Week 144)