Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study
Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study
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DOI：
10.1016/s2352-3018(20)30240-x
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发表时间：
2020-11-01
期刊：
影响因子：
16.1
通讯作者：
Llamoso, Cyril
中科院分区：
文献类型：
--
作者：
Lataillade, Max;Lalezari, Jacob P.;Llamoso, Cyril
背景Fostemsavir是一类附着抑制剂Temsavir的前药，适用于治疗经验丰富的多重耐药HIV-1患者。我们以前报道过在BRIGHTE研究的随机队列中，在8天功能性单药治疗（主要终点）后，福司他韦与安慰剂相比具有上级疗效;在这里，我们报告了计划的中期分析，直至第96周。方法BRIGHTE（NCT 02362503）是一项正在进行的多中心、两队列、3期试验，在22个国家的108个中心进行。我们招募了大量有治疗经验的成年人，（≥ 18岁）抗逆转录病毒治疗失败（HIV-1 RNA >= 400拷贝/mL）分为两个队列：随机队列，其中剩余一种或两种完全活性抗逆转录病毒药物的患者接受口服fostemsavir（600毫克，每天两次）或安慰剂与他们失败的方案相结合，持续8天，然后是fostemsavir加优化的背景治疗;或非随机队列，其中没有剩余抗逆转录病毒选择的患者从第1天开始接受口服fostemsavir（600 mg，每日两次）加优化的背景治疗。第96周中期分析的终点包括血浆HIV-1 RNA低于40拷贝/mL的受试者比例、CD 4细胞计数较基线的变化、不良事件频率、导致停药的不良事件和死亡。意向治疗暴露人群和安全性人群均包括接受至少一剂研究治疗的所有受试者。应答率（携带HIV-1 RNA的参与者比例）
Background Fostemsavir, a prodrug of the first-in-class attachment inhibitor, temsavir, is indicated for heavily treatment-experienced individuals with multidrug-resistant HIV-1. We previously reported superior efficacy of fostemsavir versus placebo in the randomised cohort of the BRIGHTE study after 8-day functional monotherapy (primary endpoint); here we report planned interim analyses through week 96.Methods BRIGHTE (NCT02362503) is an ongoing multicentre, two-cohort, phase 3 trial, done at 108 centres in 22 countries. We enrolled heavily treatment-experienced adults (>= 18 years) failing antiretroviral therapy (HIV-1 RNA >= 400 copies per mL) into two cohorts: the randomised cohort, in which patients with one or two fully active antiretrovirals remaining received oral fostemsavir (600 mg twice a day) or placebo in combination with their failing regimen for 8 days, followed by fostemsavir plus optimised background therapy; or the non-randomised cohort, in which patients with no remaining antiretroviral options received oral fostemsavir (600 mg twice a day) plus optimised background therapy from day 1. Endpoints for the week 96 interim analyses included the proportions of participants with plasma HIV-1 RNA of less than 40 copies per mL, changes from baseline in CD4 cell counts, and the frequency of adverse events, adverse events leading to discontinuation, and deaths. The intention-to-treat exposed population and the safety population both included all participants who received at least one dose of study treatment. The response rates (proportion of participants with HIV-1 RNA