Department of Pediatrics, University of California, San Francisco, CA, USA.
Digestive Health Institute, Children's Hospital Colorado and Section of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA.
Adv Ther. 2020 Jul;37(7):3299-3310. doi: 10.1007/s12325-020-01389-9. Epub 2020 May 25.
To assess the safety, efficacy, and pharmacokinetics of mini-tablet formulations of ombitasvir (OBV), paritaprevir (PTV), ritonavir, and dasabuvir (DSV) with or without ribavirin for 12 weeks in children infected with chronic hepatitis C virus (HCV) genotype (GT) 1.
This is an ongoing, open-label, Phase 2/3 study in children 3-11 years old infected with HCV GT1 who were HCV treatment-naïve and non-cirrhotic. Pediatric mini-tablet formulations of OBV, PTV, ritonavir, and DSV plus ribavirin oral solution were administered for 12 weeks based on body weight. Endpoints included SVR12, adverse events (AEs), and pharmacokinetic parameters.
Overall, 26 children received OBV, PTV, ritonavir, and DSV plus ribavirin; 14 were 3-8 years old and 12 were 9-11 years old; 35% were male; and all had chronic HCV GT1a infection. The SVR12 rate was 96% (25/26; 95% CI 81.1-99.3), with 1 child failing to achieve SVR12 due to non-adherence and treatment discontinuation. Treatment-emergent AEs of Grade ≥ 3 occurred in 3 children; 2 events in 1 child were considered serious; and none were considered treatment-related. No AEs led to discontinuation of study treatment. The most common AEs were headache (27%), fatigue (23%), pyrexia (19%), and vomiting (19%). Pharmacokinetic results showed mini-tablet formulations of OBV, PTV, DSV, and ritonavir drug exposures were comparable to the adult formulation.
The mini-tablet combination of OBV, PTV, ritonavir, and DSV plus ribavirin to treat HCV GT1a infection for 12 weeks was highly effective and suitable in children 3-11 years of age.
ClinicalTrials.gov identifier, NCT02486406.
评估迷你片剂奥贝胆酸（OBV）、帕利瑞韦（PTV）、利托那韦和达沙布韦（DSV）联合或不联合利巴韦林，用于治疗慢性丙型肝炎病毒（HCV）基因型（GT）1 感染儿童 12 周的安全性、疗效和药代动力学。
这是一项正在进行的、开放性、2/3 期研究，纳入 HCV GT1 感染且未经 HCV 治疗、非肝硬化的 3-11 岁儿童。根据体重，给予儿童口服迷你片剂 OBV、PTV、利托那韦和 DSV 联合利巴韦林口服液治疗 12 周。主要终点包括 SVR12、不良事件（AE）和药代动力学参数。
总体而言，26 例儿童接受了 OBV、PTV、利托那韦和 DSV 联合利巴韦林治疗；14 例年龄为 3-8 岁，12 例年龄为 9-11 岁；35%为男性；均为慢性 HCV GT1a 感染。SVR12 率为 96%（25/26；95%CI81.1-99.3），1 例患儿因不依从和治疗中断而未达到 SVR12。3 例患儿出现治疗后发生的≥3 级 AE；1 例患儿的 2 例事件被认为是严重的；均与治疗无关。无 AE 导致研究治疗中止。最常见的 AE 是头痛（27%）、疲劳（23%）、发热（19%）和呕吐（19%）。药代动力学结果表明，OBV、PTV、DSV 和利托那韦的迷你片剂制剂药物暴露与成人制剂相当。
OBV、PTV、利托那韦和 DSV 联合利巴韦林迷你片剂治疗 12 周 HCV GT1a 感染在 3-11 岁儿童中高度有效且适用。
ClinicalTrials.gov 标识符，NCT02486406。
