A Phase 3, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Switching to Long-acting Antiretroviral Therapy of Broadly Neutralizing Antibodies Teropavimab and Zinlirvimab in Combination With the Capsid Inhibitor Lenacapavir Twice-Yearly Versus Cabotegravir and Rilpivirine Every 8 Weeks in Virologically Suppressed Adults With HIV-1 on Oral Daily Antiretroviral Therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 590
- 试验地点
- 19
- 主要终点
- Proportion of Participants With HIV-1 ribonucleic acid (RNA) ≥ 50 Copies/mL at Week 52 as Defined by the United States (US) Food and Drug Administration (FDA) Snapshot Algorithm.
研究概览
简要总结
The goal of this clinical study is to compare how effective a long-acting injectable treatment of lenacapavir (LEN), teropavimab (TAB), and zinlirvimab (ZAB) versus (CAB) and rilpivirine (RPV) injections given every 8 weeks in adults with HIV-1 whose virus is well controlled on daily oral treatment, after 1 year (52 weeks) of the treatment.
The primary objective of this study are to evaluate the efficacy of switching to the regimen of LEN, TAB, and ZAB versus switching to CAB and RPV in virologically suppressed people with HIV-1 (PWH) as determined by the proportion of participants with HIV-1 RNA ≥ 50 copies/mL at Week 52.
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
- •Human immunodeficiency virus type 1 (HIV-1) susceptibility results from screening meeting specific criteria:
- •1) Proviral phenotypic susceptibility to both TAB and ZAB by the investigational protocol-defined assay at screening.
- •At least 1 documented HIV-1 RNA level measured between 6 months and 12 months (+2 months) prior to screening. This and any other HIV-1 RNA measurements documented in this period must be < 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). A single virologic elevation of ≥ 50 copies/mL and < 400 copies/mL (transient detectable viremia or "blips") prior to screening are acceptable if the subsequent plasma HIV-1 RNA level is < 50 copies/mL.
- •A plasma HIV-1 RNA test < 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL) within the last 6 months prior to screening.
- •1) If > 1 plasma HIV-1 RNA measurements in the last 6 months prior to screening are available, all must be < 50 copies/mL (undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL).
- •On a stable oral ARV therapy (ART) for ≥ 6 months prior to screening.
- •A change in ART regimen ≥ 3 months prior to the screening visit for reasons other than virologic failure (VF) (eg, tolerability, simplification, drug-drug interaction profile) is allowed; individuals with a change in ART regimen ≥ 3 months prior to screening must have been on the regimen for ≥ 3 months prior to screening, and all HIV-1 RNA measurements in that period must be < 50 copies/mL. There are no permitted changes to ART regimens between screening and Day
排除标准
- •History of an opportunistic infection or illness indicative of Stage 3 HIV disease.
- •History of treatment failure.
- •Known or suspected resistance to either CAB or RPV.
- •Resistance to CAB defined as the following mutations: G118R, Q148K, Q148R, T66K+L74M, E92Q+N155H, E138A+Q148R, E138K+Q148K/R, G140C+Q148R, G140S+Q148H/K/R, Y143H+N155H, and Q148R+N155H.
- •Resistance to RPV defined as the following mutations: K101E and P; E138A, G, K, R, and Q; V179L; Y181C, I, and V; Y188L; H221Y; F227C; M230I and L, and the combination of L100I/K103N.
- •Individuals with a dermatologic condition or implanted prothesis overlying the gluteal injection site for CAB + RPV.
- •Known hypersensitivity to the study intervention, its metabolites, or formulation excipients.
- •Active, serious infections (other than HIV-1) requiring therapy < 30 days prior to randomization.
- •Active tuberculosis infection.
- •Acute hepatitis of any cause < 30 days before randomization.
- •History of, or current clinical decompensated liver cirrhosis (eg, ascites, encephalopathy, or variceal bleeding) or severe hepatic impairment (Child-Pugh Class C).
- •Active malignancy requiring acute systemic therapy.
- •Have poor venous access that would limit phlebotomy or intravenous (IV) infusion of study drugs.
- •Prior use of, or exposure to, LEN or a broadly neutralizing antibody (bNAb) for HIV-
- •Prior use of, or exposure to, long-acting (LA) injectable CAB or LA injectable RPV.
- •Prior use of, or exposure to, ibalizumab, fostemsavir, or maraviroc.
- •Baseline regimen consisting of monotherapy with any single antiretroviral (ARV).
- •Treatment with immunosuppressant therapies (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies) within 4 weeks of screening (with the exception of a single short course of corticosteroids lasting ≤ 7 days) or have a comorbid condition with an anticipated need ongoing immunosuppressive treatment during the study.
- •Hepatitis C virus (HCV) antibody positive and HCV RNA detectable.
- •Chronic hepatitis B virus (HBV) infection, as determined by either:
- •Positive HBV surface antigen and negative HBV surface antibody, regardless of HBV core antibody status, at the screening visit.
- •Positive HBV core antibody and negative HBV surface antibody, regardless of HBV surface antigen status, at the screening visit.
- •Severe renal impairment-estimated glomerular filtration rate < 30 mL/min according to the Cockcroft-Gault formula.
- •Abnormal electrocardiogram (ECG) at the screening visit that is clinically significant, as determined by the investigator.
- •Any of the following laboratory values at screening:
- •Alanine aminotransferase > 5 x upper limit of normal (ULN).
- •Direct bilirubin > 1.5 x ULN.
- •Platelets < 50,000/mm^
- •Hemoglobin < 8.0 g/dL.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)
Participants will receive oral LEN 600 mg, subcutaneous (SC) LEN 927 mg, and intravenously (IV) infusions of TAB and ZAB on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. Every 26 weeks, participants will receive SC LEN and IV infusions of TAB and ZAB up to Week 92.
After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discontinuing the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.
干预措施: Lenacapavir Tablet (Drug)
Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)
Participants will receive oral LEN 600 mg, subcutaneous (SC) LEN 927 mg, and intravenously (IV) infusions of TAB and ZAB on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. Every 26 weeks, participants will receive SC LEN and IV infusions of TAB and ZAB up to Week 92.
After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discontinuing the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.
干预措施: Teropavimab (Drug)
Treatment Group 2: Cabotegravir (CAB) + Rilpivirine (RPV)
Participants will discontinue their baseline oral antiretroviral therapy (ART) and will receive intramuscular (IM) CAB 600 mg + RPV 900 mg on Day 1, Week 4 and then every 8 weeks for up to 92 weeks.
After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discounting the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.
干预措施: Cabotegravir (Drug)
Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)
Participants will receive oral LEN 600 mg, subcutaneous (SC) LEN 927 mg, and intravenously (IV) infusions of TAB and ZAB on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. Every 26 weeks, participants will receive SC LEN and IV infusions of TAB and ZAB up to Week 92.
After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discontinuing the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.
干预措施: Lenacapavir (Drug)
Treatment Group 1: Lenacapavir(LEN)+ Teropavimab(TAB)+ Zinlirvimab (ZAB)
Participants will receive oral LEN 600 mg, subcutaneous (SC) LEN 927 mg, and intravenously (IV) infusions of TAB and ZAB on Day 1. Participants will self-administer oral LEN 600 mg on Day 2. Every 26 weeks, participants will receive SC LEN and IV infusions of TAB and ZAB up to Week 92.
After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discontinuing the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.
干预措施: Zinlirvimab (Drug)
Treatment Group 2: Cabotegravir (CAB) + Rilpivirine (RPV)
Participants will discontinue their baseline oral antiretroviral therapy (ART) and will receive intramuscular (IM) CAB 600 mg + RPV 900 mg on Day 1, Week 4 and then every 8 weeks for up to 92 weeks.
After Week 92, eligible participants will have an option to continue LEN + TAB + ZAB in the extension phase, until completion of the extension phase, permanently discounting the extension phase or the extension is discontinued at the sponsor's sole discretion, whichever occurs first.
干预措施: Rilpivirine (Drug)
结局指标
主要结局
Proportion of Participants With HIV-1 ribonucleic acid (RNA) ≥ 50 Copies/mL at Week 52 as Defined by the United States (US) Food and Drug Administration (FDA) Snapshot Algorithm.
时间窗: Week 52
次要结局
- Proportion of Participants with HIV-1 RNA < 50 copies/mL at Week 92 as Determined by the US FDA Snapshot Algorithm.(Week 92)
- Proportion of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 92 as Defined by the US FDA Snapshot Algorithm.(Week 92)
- Proportion of Participants With HIV-1 RNA < 50 Copies/mL at Week 52 as Determined by the US FDA Snapshot Algorithm(Week 52)
- Change From Baseline in clusters of differentiation 4 (CD4) (CD4)+ T-cell Counts at Week 52(Baseline, Week 52)
- Change From Baseline in CD4+ T-cell Counts at Week 92(Baseline, Week 92)
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events (AEs)(Up to Week 92)
- Percentages of Participants Prematurely Discontinuing Their Study Treatment due to an AE(Up to Week 92)
- Trough Concentrations for LEN, TAB, and ZAB at Week 26(Week 26)
- Trough Concentrations for LEN, TAB, and ZAB at Week 52(Week 52)
- Trough Concentrations for LEN, TAB, and ZAB at Week 104(Week 104)
- Percentages of Participants With Antidrug Antibodies (ADAs) and Neutralizing Antibodies (NAbs) of TAB(Up to 92 Weeks)
- Percentages of Participants With of ADAs and NAbs of ZAB(Up to 92 Weeks)