Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Adolescents With Chronic Hepatitis C Virus: Part 1 of the DORA Study
Pharmacokinetics, Safety, and Efficacy of Glecaprevir/Pibrentasvir in Adolescents With Chronic Hepatitis C Virus: Part 1 of the DORA Study
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DOI：
10.1002/hep.30840/suppinfo
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发表时间：
2019-08-13
期刊：
影响因子：
13.5
通讯作者：
Sokal, Etienne
中科院分区：
文献类型：
--
作者：
Jonas, Maureen M.;Squires, Robert H.;Sokal, Etienne
glecaprevir和pibrentasvir （G/P）的泛型方案被批准用于治疗慢性丙型肝炎病毒（HCV）感染的成人，并在临床试验中取得了很高的治愈率。批准的儿科治疗方案可能包括利巴韦林。儿童患者的泛型治疗方案仍然是一个未满足的需求。DORA是一项正在进行的2/3期、非随机、开放标签研究，评估G/P在慢性HCV儿科患者中的药代动力学（PK）、安全性和有效性。该分析包括研究的第一部分，在12-17岁的青少年患者中进行，根据成人使用的适应症持续时间，给予G/P （300 mg/120 mg）成人方案，每天一次，持续8-16周。患者要么未接受过治疗，要么已接受过干扰素治疗。主要的PK终点是glecaprevir和pibrentasvir的稳态暴露；主要疗效终点是治疗后12周的持续病毒学应答（SVR12）。次要疗效终点是治疗时病毒学失败、复发和再感染。监测安全性和耐受性。第一部分纳入了48例基因型为1、2、3或4的青少年患者，其中47例给予G/P。47例患者（100%）均达到SVR12。未发生治疗期病毒学失败或复发。glecaprevir和pibrentasvir的PK暴露与成人暴露相当。无不良事件（ae）导致停药，无严重ae发生。结论：接受G/P治疗的青少年慢性HCV感染患者与成人的暴露量相当，SVR12率为100%，安全性与成人一致。在短短8周的治疗中，这种泛型方案在青少年人群中显示出100%的疗效。glecaprevir和pibrentasvir （G/P）的泛型方案被批准用于治疗慢性丙型肝炎病毒（HCV）感染的成人，并在临床试验中取得了很高的治愈率。批准的儿科治疗方案可能包括利巴韦林。儿童患者的泛型治疗方案仍然是一个未满足的需求。DORA是一项正在进行的2/3期、非随机、开放标签研究，评估G/P在慢性HCV儿科患者中的药代动力学（PK）、安全性和有效性。该分析包括研究的第一部分，在12-17岁的青少年患者中进行，根据成人使用的适应症持续时间，给予G/P （300 mg/120 mg）成人方案，每天一次，持续8-16周。患者要么未接受过治疗，要么已接受过干扰素治疗。主要的PK终点是glecaprevir和pibrentasvir的稳态暴露；主要疗效终点是治疗后12周的持续病毒学应答（SVR12）。次要疗效终点是治疗时病毒学失败、复发和再感染。监测安全性和耐受性。第一部分纳入了48例基因型为1、2、3或4的青少年患者，其中47例给予G/P。47例患者（100%）均达到SVR12。未发生治疗期病毒学失败或复发。glecaprevir和pibrentasvir的PK暴露与成人暴露相当。无不良事件（ae）导致停药，无严重ae发生。结论：接受G/P治疗的青少年慢性HCV感染患者与成人的暴露量相当，SVR12率为100%，安全性与成人一致。在短短8周的治疗中，这种泛型方案在青少年人群中显示出100%的疗效。
The pangenotypic regimen of glecaprevir and pibrentasvir (G/P) is approved to treat adults with chronic hepatitis C virus (HCV) infection and has yielded high cure rates in adults in clinical trials. Approved treatment options for pediatrics may include ribavirin. A pangenotypic regimen for pediatric patients remains an unmet need. DORA is an ongoing phase 2/3, nonrandomized, open-label study evaluating the pharmacokinetics (PK), safety, and efficacy of G/P in pediatric patients with chronic HCV. This analysis includes Part 1 of the study, conducted in adolescent patients 12-17 years of age given the adult regimen of G/P (300 mg/120 mg) once daily for 8-16 weeks according to the indication durations used in adults. Patients were either treatment naive or experienced with interferon-based regimens. The primary PK endpoint was steady-state exposures for glecaprevir and pibrentasvir; the primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12). The secondary efficacy endpoints were on-treatment virologic failure, relapse, and reinfection. Safety and tolerability were monitored. Part 1 enrolled 48 adolescent patients infected with genotypes 1, 2, 3, or 4, of whom 47 were administered G/P. All 47 patients (100%) achieved SVR12. No on-treatment virologic failures or relapses occurred. PK exposures of glecaprevir and pibrentasvir were comparable to exposures in adults. No adverse events (AEs) led to treatment discontinuation, and no serious AEs occurred. Conclusion: Adolescent patients with chronic HCV infection treated with G/P achieved a comparable exposure to adults, 100% SVR12 rate, and safety profile consistent with that in adults. This pangenotypic regimen demonstrated 100% efficacy within the adolescent population in as little as 8 weeks of treatment.The pangenotypic regimen of glecaprevir and pibrentasvir (G/P) is approved to treat adults with chronic hepatitis C virus (HCV) infection and has yielded high cure rates in adults in clinical trials. Approved treatment options for pediatrics may include ribavirin. A pangenotypic regimen for pediatric patients remains an unmet need. DORA is an ongoing phase 2/3, nonrandomized, open-label study evaluating the pharmacokinetics (PK), safety, and efficacy of G/P in pediatric patients with chronic HCV. This analysis includes Part 1 of the study, conducted in adolescent patients 12-17 years of age given the adult regimen of G/P (300 mg/120 mg) once daily for 8-16 weeks according to the indication durations used in adults. Patients were either treatment naive or experienced with interferon-based regimens. The primary PK endpoint was steady-state exposures for glecaprevir and pibrentasvir; the primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12). The secondary efficacy endpoints were on-treatment virologic failure, relapse, and reinfection. Safety and tolerability were monitored. Part 1 enrolled 48 adolescent patients infected with genotypes 1, 2, 3, or 4, of whom 47 were administered G/P. All 47 patients (100%) achieved SVR12. No on-treatment virologic failures or relapses occurred. PK exposures of glecaprevir and pibrentasvir were comparable to exposures in adults. No adverse events (AEs) led to treatment discontinuation, and no serious AEs occurred. Conclusion: Adolescent patients with chronic HCV infection treated with G/P achieved a comparable exposure to adults, 100% SVR12 rate, and safety profile consistent with that in adults. This pangenotypic regimen demonstrated 100% efficacy within the adolescent population in as little as 8 weeks of treatment.