Objective: To investigate the efficacy and safety of the new investigational drug pegylated interferon α-2b (Peg-IFN-α-2b) (Y shape, 40 kD) injection (180 µg/week) combined with ribavirin in the treatment of patients with genotype 1/6 chronic hepatitis C (CHC), with standard-dose Peg-IFN-α-2a combined with ribavirin as a positive control. Methods: A multicenter, randomized, open-label, and positive-controlled phase III clinical trial was performed. Eligible patients with genotype 1/6 CHC were screened out and randomly divided into Peg-IFN-α-2b(Y shape, 40kD) group and Peg-IFN-α-2a group at a ratio of 2:1. The patients in both groups were given oral ribavirin for 48 weeks in addition and then followed up for 24 weeks after drug withdrawal. Abbott Real Time HCV Genotype II was used to determine HCV genotype, and Cobas TaqMan quantitative real-time PCR was used to measure HCV RNA level at 0, 4, 12, 24, 48, and 72 weeks. Adverse events were recorded in detail. The primary efficacy endpoint was sustained virological response (SVR), and a non-inferiority test was also performed. Results: A total of 561 patients with genotype 1/6 CHC were enrolled, among whom 529 received treatment; 90.9% of these patients had genotype 1 CHC. The data of the full analysis set showed that SVR rate was 69.80% (95% CI 65.00%-74.60%) in the trial group and 74.16% (95% CI 67.73%-80.59%) in the control group (P = 0.297 0). The data of the per protocol set (PPS) showed that SVR rate was 80.63% (95% CI 76.04%-85.23%) in the trial group and 81.33% (95% CI 75.10%-87.57%) in the control group (P = 0.849 8), and the 95% CI of rate difference conformed to the non-inferiority standard. The analysis of the PPS population showed that of all subjects, 47.9% achieved rapid virologic response, with a positive predictive value of 93.8%. The incidence rate of adverse events was 96.30% in the trial group and 94.94% in the control group, and the incidence rate of serious adverse events was 5.13% in the trail group and 5.06% in the control group. Conclusion: In the regimen of Peg-IFN-α combined with ribavirin for the treatment of genotype 1/6 CHC, the new investigational drug Peg-IFN-α-2b(Y shape, 40 kD) has comparable clinical effect and safety to the control drug Peg-IFN-α-2a.
目的： 以标准剂量聚乙二醇干扰素（Peg-IFN）α-2a联合利巴韦林作为阳性对照，评价新型试验药物Peg-IFNα-2b（Y型，40 kD）注射液（180 μg/周）联合利巴韦林治疗1/6型慢性丙型肝炎（CHC）患者的疗效和安全性。 方法： 本研究为多中心、随机开放、阳性药物对照的Ⅲ期临床试验。筛选合格的1/6型CHC患者按照2∶1的比例随机分配到Peg-IFNα-2b（Y型，40 kD）组和Peg-IFNα-2a组，同时口服利巴韦林，疗程48周，停药随访24周。用Abbott RealTime HCV Genotype II检测HCV基因型，用Cobas TaqMan实时定量PCR检测0、4、12、24、48周和72周HCV RNA水平。详细记录不良事件。主要疗效指标为持续病毒学应答率，并进行非劣效检验。定量指标的描述将计算均数、标准差、中位数、最小值、最大值、四分位间距。分类指标的描述用各类的例数及百分数。主要疗效指标采用全分析集和符合方案分析集进行评价。计算试验组和对照组治疗后病毒应答率差值（试验组-对照组）及其双侧95%可信区间（CI），根据CI的下限，判断是否达到非劣效标准，当95% CI的下限大于-12%时，非劣效结论成立。统计分析应用SAS统计分析软件9.2版。根据不同的数据类型及特点分别采用卡方检验、秩和检验、Q检验等。 结果： 实际入组1/6型CHC患者561例，实际治疗529例，其中1型占90.9%。全分析集数据显示，试验组和对照组患者的持续病毒学应答率分别是69.80%（95% CI：65.00%～74.60%）和74.16%（95% CI：67.73%～80.59%）（P = 0.297 0）。符合方案分析集数据显示，试验组和对照组患者的持续病毒学应答率分别是80.63%（95% CI：76.04%～85.23%）和81.33%（95% CI：75.10%～87.57%）（P = 0.849 8），率差的95% CI符合非劣效标准。符合方案分析集人群分析结果显示，47.9%的受试者获得了快速病毒学应答，快速病毒学应答的阳性预测值为93.8%。试验组和对照组不良事件发生率相似，分别是96.30%和94.94%，严重不良事件的发生率分别是5.13%和5.06%。 结论： Peg-IFNα联合利巴韦林治疗基因1/6型CHC的方案中，新型试验药物Peg-IFNα-2b（Y型，40 kD）具有与对照药物Peg-IFNα-2a相似的疗效和安全性。.
Keywords: Clinical trial; Hepatitis C, chronic; Interferons.