Phase 3 studies in patients with chronic hepatitis B have shown tenofovir alafenamide to have non-inferior efficacy to tenofovir disoproxil fumarate, with improved renal and bone safety. We conducted this study to evaluate the safety and efficacy of switching to tenofovir alafenamide in participants with chronic hepatitis B and renal or hepatic impairment. This open-label, multicentre, phase 2 study was done in eight countries or territories at 30 sites. We recruited adults (≥18 years) with chronic hepatitis B who were virally suppressed on nucleoside or nucleotide analogues and had renal impairment (part A: moderate or severe in cohort 1 [estimated glomerular filtration rate by the Cockcroft–Gault formula (eGFR) 15–59 mL/min] or end-stage renal disease [eGFR <15 mL/min] on haemodialysis in cohort 2) or hepatic impairment including decompensation (part B: Child–Turcotte–Pugh score 7–12). Participants switched to 25 mg of tenofovir alafenamide given orally once daily for 96 weeks. The primary endpoint was the proportion of participants with viral suppression (HBV DNA <20 IU/mL) at week 24 by missing-equals-failure analysis. Efficacy (full analysis set) and safety (safety analysis set) analyses included all enrolled participants who received at least one dose of the study drug. Week 96 safety was assessed, including renal and bone parameters. This trial is registered at , , and is completed. 124 participants (93 in part A [78 in cohort 1 and 15 in cohort 2] and 31 in part B) were enrolled between Aug 11, 2017, and Oct 17, 2018, and included in the full and safety analysis sets. 106 (85%) participants completed the study. There were 69 (74%) men and 24 (26%) women in part A and 21 (68%) men and ten (32%) women in part B. At week 24, 91 (97·8%, 95% CI 92·4 to 99·7) of 93 individuals in part A (76 [97·4%, 91·0 to 99·7] of 78 in cohort 1 and 15 [100·0%, 78·2 to 100·0] of 15 in cohort 2) and 31 (100·0%, 88·8 to 100·0) in part B had HBV DNA of less than 20 IU/mL. By week 96, the most common adverse event was upper respiratory tract infection, which occurred in 14 (15%) participants in part A and in six (19%) participants in part B. Serious adverse events occurred in 20 (22%) part A participants and in ten (32%) part B participants; none were related to treatment. No treatment-related deaths occurred. At week 96, median change in estimated glomerular filtration rate (Cockcroft-Gault method) was 1·0 mL/min (IQR −2·8 to 4·5) in cohort 1 and −2·4 mL/min (−11·4 to 10·7) in part B. Mean changes in spine and hip bone mineral density were 1·02% (SD 4·44) and 0·20% (3·25) in part A and −0·25% (3·91) and 0·28% (3·25) in part B. Tenofovir alafenamide might offer continued antiviral efficacy and a favourable safety profile for patients with renal or hepatic impairment and chronic hepatitis B switching from tenofovir disoproxil fumarate or other antivirals. Gilead Sciences.

中文翻译：

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对于病毒学抑制的慢性乙型肝炎和肾或肝功能不全的患者改用替诺福韦艾拉酚胺：一项开放标签、多中心、2 期研究的最后第 96 周结果


针对慢性乙型肝炎患者的 3 期研究表明，替诺福韦艾拉酚胺的疗效不逊色于富马酸替诺福韦二吡呋酯，并改善了肾脏和骨骼安全性。我们进行这项研究是为了评估患有慢性乙型肝炎和肾或肝功能损害的参与者改用替诺福韦艾拉酚胺的安全性和有效性。这项开放标签、多中心、2 期研究在 8 个国家或地区的 30 个地点进行。我们招募了患有慢性乙型肝炎的成年人（≥18岁），他们在核苷或核苷酸类似物的作用下受到病毒抑制，并且患有肾功能不全（A部分：队列1中的中度或重度[根据Cockcroft-Gault公式（eGFR）估计的肾小球滤过率15] –59 mL/min] 或队列 2 中进行血液透析的终末期肾病 [eGFR <15 mL/min]）或肝功能损害，包括失代偿（B 部分：Child-Turcotte-Pugh 评分 7-12）。参与者改用 25 毫克替诺福韦艾拉酚胺，每天口服一次，持续 96 周。主要终点是通过缺失等于失败分析，在第 24 周时出现病毒抑制（HBV DNA <20 IU/mL）的参与者比例。功效（完整分析集）和安全性（安全分析集）分析包括所有接受至少一剂研究药物的入组参与者。第 96 周评估了安全性，包括肾脏和骨骼参数。该试验在 、 、 处注册并已完成。 2017年8月11日至2018年10月17日期间入组了124名参与者（A部分93人[第1组78人，第2组15人]和B部分31人），并纳入完整分析组和安全分析组。 106 名 (85%) 参与者完成了研究。 A 部分有 69 名男性 (74%) 和 24 名女性 (26%)，B 部分有 21 名男性 (68%) 和 10 名女性 (32%)。 在第 24 周，A 部分 93 名个体中的 91 名（97·8%，95% CI 92·4 至 99·7）（队列 1 中 78 名个体中的 76 [97·4%，91·0 至 99·7]）队列 2) 中的 15 例中有 15 例 [100·0%, 78·2 至 100·0] 和 B 部分中的 31 例 (100·0%, 88·8 至 100·0) HBV DNA 低于 20 IU/mL 。到第 96 周，最常见的不良事件是上呼吸道感染，A 部分的 14 名参与者（15%）和 B 部分的 6 名参与者（19%）发生了严重不良事件。20 名参与者（22%）发生了严重不良事件。 A 部分参与者和 10 名 (32%) B 部分参与者；没有一个与治疗有关。没有发生与治疗相关的死亡。第 96 周时，队列 1 中估计肾小球滤过率（Cockcroft-Gault 方法）的中位变化为 1·0 mL/min（IQR -2·8 至 4·5），队列 1 为 -2·4 mL/min（-11·IQR）。 B 部分的脊柱和髋骨矿物质密度的平均变化为 1·02% (SD 4·44) 和 0·20% (3·25)，A 部分为 -0·25% (SD 4·44) 和 -0·25% ( B 部分中的 3·91) 和 0·28% (3·25)。替诺福韦艾拉酚胺可能会为患有肾或肝损伤以及从富马酸替诺福韦二吡呋酯或其他抗病毒药物转换为慢性乙型肝炎的患者提供持续的抗病毒功效和良好的安全性。吉利德科学。