A Phase 3, Randomized, Open-Label, Active-Controlled Study to Evaluate a Switch to an Oral Weekly Islatravir/Lenacapavir Regimen in People With HIV-1 Who Are Virologically Suppressed on Standard of Care
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 600
- 试验地点
- 197
- 主要终点
- Proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as Determined by the United States (US) Food and Drug Administration (FDA)-defined Snapshot Algorithm
研究概览
简要总结
The goal of this clinical study is to learn more about the safety and efficacy of switching to a once weekly tablet of islatravir/lenacapavir (ISL/LEN) regimen versus continuing standard of care treatment in people with human immunodeficiency virus (PWH) who are virologically suppressed (HIV-1 RNA levels < 50 copies/mL) on a stable standard of care regimen for ≥ 6 months prior to screening. The standard of care includes 2 or 3 medicines, antiretroviral agents (ARVs).
The primary objective of the study is to evaluate the efficacy of switching to oral weekly ISL/LEN tablet regimen versus continuing standard of care in virologically suppressed PWH 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
- •HIV-1 RNA < 50 copies/mL for ≥ 6 months before screening, as documented by:
- •One HIV-1 RNA < 50 copies/mL immediately preceding the 24 weeks period prior to screening.
- •Within 24 weeks prior to screening, if HIV-1 RNA results are available, all levels must be < 50 copies/mL.
- •During the 6 to 12 months period prior to screening, transient detectable viremia ≥ 50 copies/mL is acceptable ("blip") as long as it is not confirmed on 2 consecutive visits.
- •Plasma HIV-1 RNA levels < 50 copies/mL at screening.
- •Are receiving guideline-recommended standard of care treatment such as International Antiviral Society (IAS), Department of Health and Human Services (DHHS), European AIDS Clinical Society (EACS) consisting of 2 or 3 ARVs for ≥ 6 months prior to screening and willing to continue until Day
- •Individuals in Treatment Group 2 must also be willing to continue their standard of care through at least Week
- •Individuals assigned female at birth and of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified methods of contraception.
排除标准
- •Prior virologic failure.
- •Prior use of, or exposure to, ISL or LEN.
- •Active, serious infections requiring parenteral therapy within 30 days before randomization.
- •Active tuberculosis infection.
- •Acute hepatitis within 30 days before randomization.
- •Hepatitis B virus (HBV) infection, as determined below at the screening visit:
- •positive HBV surface antigen OR
- •positive HBV core antibody and negative HBV surface antibody. Note: individuals found to be susceptible to HBV infection (eg negative hepatitis B surface antibody at the screening visit, regardless of prior HBV vaccination history) should be recommended to receive HBV vaccination.
- •Active hepatitis C virus (HCV) coinfection, defined as detectable HCV RNA. Note: individuals with prior/inactive HCV infection (defined as undetectable HCV RNA) may be enrolled.
- •Any of the following laboratory values at screening:
- •Creatinine clearance (CLcr) ≤ 30 mL/min according to the Cockcroft-Gault formula
- •Alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN)
- •Direct bilirubin > 1.5 x ULN
- •Platelets < 50,000/μL
- •Hemoglobin < 8.0 g/dL
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
ISL/LEN
Participants will receive an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards up to Week 96.
干预措施: ISL/LEN (Drug)
Standard of Care Treatment
Participants will continue standard of care treatment with 2-3 ARVs up to Week 96:
- Integrase Strand Transfer Inhibitor (INSTI) class: INSTI combined with 1 or 2 nucleoside reverse transcriptase inhibitors (NRTIs; bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®), dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC), DTG+ TAF or TDF (TXF)/emtricitabine (FTC; Emtriva®), DTG/tenofovir disoproxil fumarate (TDF; Viread®)/3TC, DTG/3TC, raltegravir (RAL) + TXF/FTC, RAL+TDF/3TC, elvitegravir (EVG; Vitekta®)/cobicistat (c; Tybost®)/TXF/FTC), or
- PI class: Boosted protease inhibitor (PI) combined with 2 NRTIs (darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF; coformulated), boosted darunavir (DRV)+TXF/FTC, boosted DRV+TDF/3TC), or
- NNRTI class: Nonnucleoside reverse transcriptase inhibitor (NNRTI) combined with 2 NRTIs (doravirine (DOR)/TDF/3TC, DOR+TXF/FTC, DOR+TDF/3TC, rilpivirine (RPV)/TXF/FTC, RPV+TXF/FTC, RPV+TDF/3TC)
干预措施: ISL/LEN (Drug)
Standard of Care Treatment
Participants will continue standard of care treatment with 2-3 ARVs up to Week 96:
- Integrase Strand Transfer Inhibitor (INSTI) class: INSTI combined with 1 or 2 nucleoside reverse transcriptase inhibitors (NRTIs; bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF; coformulated; Biktarvy®), dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC), DTG+ TAF or TDF (TXF)/emtricitabine (FTC; Emtriva®), DTG/tenofovir disoproxil fumarate (TDF; Viread®)/3TC, DTG/3TC, raltegravir (RAL) + TXF/FTC, RAL+TDF/3TC, elvitegravir (EVG; Vitekta®)/cobicistat (c; Tybost®)/TXF/FTC), or
- PI class: Boosted protease inhibitor (PI) combined with 2 NRTIs (darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF; coformulated), boosted darunavir (DRV)+TXF/FTC, boosted DRV+TDF/3TC), or
- NNRTI class: Nonnucleoside reverse transcriptase inhibitor (NNRTI) combined with 2 NRTIs (doravirine (DOR)/TDF/3TC, DOR+TXF/FTC, DOR+TDF/3TC, rilpivirine (RPV)/TXF/FTC, RPV+TXF/FTC, RPV+TDF/3TC)
干预措施: Antiretroviral Combinations (Drug)
Extension Phase
At the end of randomized treatment visit, if safety and efficacy of ISL/LEN are demonstrated following review of randomized data, participants will be given the option to receive ISL/LEN tablets in an extension phase until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first.
Participants receiving ISL/LEN during the randomized phase will continue to take ISL/LEN weekly.
Participants receiving standard of care during the randomized phase will take an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards.
干预措施: ISL/LEN (Drug)
结局指标
主要结局
Proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 48 as Determined by the United States (US) Food and Drug Administration (FDA)-defined Snapshot Algorithm
时间窗: Week 48
次要结局
- Proportion of Participants with HIV-1 RNA ≥ 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm(Week 96)
- Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 48 as Determined by the US FDA-defined Snapshot Algorithm(Week 48)
- Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 96 as Determined by the US FDA-defined Snapshot Algorithm(Week 96)
- Change from Baseline in clusters of differentiation 4 (CD4) T-Cell Count at Week 48(Baseline, Week 48)
- Change from Baseline in CD4 T-Cell Count at Week 96(Baseline, Week 96)
- Proportion of Participants Discontinuing ISL/LEN due to Treatment-Emergent Adverse Events (TEAEs)(First dose date up to Week 96)