磷酸安泰他韦联合英强布韦治疗成人慢性丙型肝炎的有效性和安全性——Ⅱ期临床研究

A phaseⅡclinical study of the efficacy and safety of antaitasvir phosphate combined with yiqibuvir for the treatment of chronic hepatitis C in adults

目的评估100 mg或200 mg磷酸安泰他韦与英强布韦联合给药12周在各基因型、无肝硬化或有代偿期肝硬化的慢性丙型肝炎患者中的疗效和安全性。方法选取慢性丙型肝炎患者(无肝硬化或有代偿期肝硬化)按1∶1比例随机分配到磷酸安泰他韦100 mg+英强布韦600 mg组(100 mg组)或磷酸安泰他韦200 mg+英强布韦600 mg组(200 mg组)中,连续给药12周,每日1次,停药后观察24周,观察两组患者在停药后12周的持续病毒学应答(SVR12),同时评估用药安全性。尽可能完全并且接近包括所有随机化病例的意向性分析的思想,定义所有经随机化分组且至少接受过1次试验用药品的受试者构成本研究的全分析集。所有至少接受过1次试验用药品的受试者(无论是否参与随机化分组),构成本研究的安全集。所有疗效终点与安全性数据均采用描述统计量进行汇总。主要疗效终点为SVR12,在全分析集中进行主要分析。计算试验药物组(磷酸安泰他韦胶囊联合英强布韦片)实现“HCV RNA<定量下限”的受试者例数、百分比。安全性分析基于安全性分析集进行汇总。结果共纳入120例受试者,100 mg组59例,200 mg组61例。119例完成研究,1例受试者因失访提前退出研究;3例受试者发生病毒学复发。全分析集分析结果显示总体SVR12为96.7%(116/120),其中100 mg组为98.3%(58/59),200 mg组为95.1%(58/61)。代偿期肝硬化受试者总体SVR12为100%(14/14),无肝硬化受试者总体SVR12为96.2%(102/106),其中100 mg组无肝硬化受试者SVR12为98.1%(52/53),200 mg组无肝硬化受试者SVR12为94.3%(50/53)。共55.0%受试者发生治疗期不良事件(TEAEs),共33.3%受试者发生与试验药物相关TEAEs,两组TEAEs的发生率可比。发生率≥5%与试验药物相关的TEAEs为高尿酸血症与高胆固醇血症。未发生不良事件通用术语评价事件≥3级与试验药物相关TEAEs、与试验药物相关的严重TEAEs、导致试验药物暂停或停用TEAEs、导致终止治疗TEAEs、导致提前退出或导致死亡TEAEs。结论磷酸安泰他韦100 mg或200 mg联合英强布韦600 mg在各基因型、无肝硬化或代偿期肝硬化慢性丙型肝炎受试者中疗效显著,安全性良好。

ObjectiveTo evaluate the efficacy and safety of antaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir for 12 weeks in patients with various genotypes of chronic hepatitis C,without cirrhosis or compensated stage cirrhosis.MethodsPatients with chronic hepatitis C(without cirrhosis or compensated stage cirrhosis)were randomly assigned to the antaitasvir phosphate 100 mg+yiqibuvir 600 mg group(100 mg group)or the antaitasvir phosphate 200 mg+yiqibuvir 600 mg group(200 mg group)in a 1∶1 ratio.The drugs were continuously administered once a day for 12 weeks and observed for 24 weeks after drug withdrawal.The drug safety profile was assessed concurrently with the observation of the sustained virological response(SVR12)in the two patient groups 12 weeks following the drug cessation.The intention-to-treat concept was used to define as closely as possible a full analysis set,including all randomized cases who received the experimental drug at least once.The safety set was collected from all subjects who received the experimental drug at least once(regardless of whether they participated in the randomization group)in this study.All efficacy endpoints and safety profile data were summarized using descriptive statistics.The primary efficacy endpoint was SVR12.The primary analysis was performed on a full analysis set.The frequency and proportion of cases were calculated in the experimental drug group(antaitasvir phosphate capsules combined with yiqibuvir tablets)that achieved"HCV RNA<lower limit of quantification."The safety profile analysis was summarized based on the safety analysis set.ResultsA total of 120 cases were enrolled,with 59 in the 100 mg group and 61 in the 200 mg group.119 subjects completed the study,and one subject withdrew early due to a loss of follow-up.Three subjects had a virological recurrence.The results of the full analysis set showed that the overall SVR12 was 96.7%(116/120),with 98.3%(58/59)in the 100 mg group and 95.1%(58/61)in the 200 mg group.The overall SVR12 of subjects with compensated stage cirrhosis was 100%(14/14),while those without cirrhosis had 96.2%(102/106).Among them,the SVR12 of subjects without cirrhosis in the 100 mg group was 98.1%(52/53),and in the 200 mg group,it was 94.3%(50/53).A total of 55.0%of subjects had treatment-emergent adverse events(TEAEs).A total of 33.3%of subjects had TEAEs occurrences related to the experimental drug.The TEAE incidences in the two groups were comparable.Hyperuricemia and hypercholesterolemia were TEAEs associated with the experimental drug,with an incidence rate of≥5%.There were no TEAEs occurrences with a CTCAE grade≥3 and severity that were causing treatment suspension or cessation,termination,early withdrawal,or death with relation to the experimental drug.ConclusionAntaitasvir phosphate 100 mg or 200 mg combined with yiqibuvir 600 mg has apparent efficacy and a good safety profile in subjects with various genotypes of chronic hepatitis C,without cirrhosis or compensated stage cirrhosis.