EASL 2018 FRI-328 每两周ro干扰素α-2b安全性较高 乙型肝炎e抗

StephenW

EASL 2018 FRI-328
Every-two-week ropegienterferon alfa-2b is safe with higher
hepatitis B e antigen seroconversion rate in interferon naive
patients with chronic hepatitis B infection: A phase 2, open label,
randomized, active control, dose finding study
Y.-W. Huang1, P.-J. Chen2, C.-W. Hsu3, S.-N. Lu4, M.-L. Yu5, C.-W. Su6,
W.-W. Su7, R.-N. Chien8, C.-S. Hsu9, S.-J. Hsu10, H.-C. Lai11, K. Tseng12.
1Cathay General Hospital Medical Center, Liver Center, Taipei, Taiwan;
2Department of Medical Research, National Taiwan University, Taiwan;
3Linkou Chang Gung Memorial Hospital, Division of
Hepatogastroenterology, Department of Internal Medicine, Taipei;
4Kaohsiung Chang Gung Memorial Hospital, Divsion of
Hepatogastroenterology; 5Kaohsiung Medical University Hospital,
Hepatobiliary Section, Department of Internal Medicine, and Hepatitis
Center, Kaohsiung, Taiwan; 6Taipei Veterans General Hospital, Division of
Hepatogastroenterology, Department of Internal Medicine, Taipei,
Taiwan; 7Changhua Christian Hospital, Department of Internal
Medicine, Changhua, Taiwan; 8Keelung Chang Gung Memorial Hospital,
Division of Hepatogastroenterology, Department of Internal Medicine,
Keelung; 9Taipei Tzu Chi General Hospital, Division of Gastroenterology
and Hepatology, Department of Internal Medicine, New Taipei City,
Taiwan; 10National Taiwan University Hospital Yun-Lin Branch, Division
of Gastroenterology and Hepatology, Department of Internal Medicine,
Yunlin, Taiwan; 11China Medical University Hospital, Division of
Hepatogastroenterology, Department of Internal Medicine, Taichung,
Taiwan; 12PharmaEssentia Corp, Medical Research, Taipei, Taiwan
Email: [email protected]
Background and Aims: Ropeginterferon alfa-2b (P1101) is a novel
mono-pegylated interferon alfa-2b with longer duration of action,
allowing every-two-week (q2w) injection with high tolerability
shownfromprevious studies. This studyaims to find the optimal dose
of P1101 by comparing antiviral activity, and safety across treatment
groups in interferon naïve patients with chronic hepatitis B virus
(HBV) infection.
Method: Thirty-one hepatitis B e antigen (HBeAg)-positive subjects
with baseline HBV DNA > 20,000IU/ml and 31 HBeAg-negative
subjects with baseline HBV DNA > 2,000IU/ml were randomized at
1:1:1 ratio to subcutaneous treatment of q2w P1101350 μg (Group 1),
q2w P1101 450 μg (Group 2), or weekly (q1w) peginterferon alfa-2a
180 μg (Group 3, control) respectively. Every patient received 48-week
treatment (TW48) and 24-week post-treatment follow-up (FW24).
Results: In HBeAg (+) subjects, cumulative HBeAg seroconversion
ratewas 27% (3/11), 36% (4/11), 11% (1/9) (p = 0.21) with median time
to HBeAg seroconversion of 24, 24, and 48 weeks (p = 0.28), in Group
1, 2, 3 respectively. At FW24, HBV DNA < 2,000 IU/ml was 27% (3/11),
0% (0/11), and 22% (2/9) (p = 0.22), hepatitis B surface antigen
(HBsAg) < 1,500 IU/mlwas 46% (5/11),18% (2/11),11% (1/9) (p = 0.27),
anti-HBe positive ratewas 46% (5/11), 46% (5/11), 18% (2/9) (p = 0.59)
in Group 1, 2, 3 respectively. In HBeAg (-) subjects at FW24, HBV DNA
< 2,000 IU/ml was 10% (1/10), 36% (4/11), 50% (5/10) (p = 0.17) and
HBsAg < 1,500 IU/ml was 80% (8/10), 91% (10/11), 90% (9/10) (p =
0.83), in Group 1, 2, 3 respectively. HBeAg (+) and (−) patients pooled
together, 10% (2/21), 5% (1/22), 11% (2/19) discontinued treatment
due to adverse events (AEs) in Group 1, 2, 3 respectively. The AEs for
discontinuationwere Grade 3myocardial infarction (MI) and Grade 4
alanine aminotransferase (ALT) increased in Group 1, multiple Grade
1 AEs in 1 subject of Group 2, and Grade 3 ALT increased in 2 subjects
of Group 3. The subject with MI has risk factors of smoking, and
hyperlipidemia. About 14% (3/21), 14% (3/22), 11% (2/19) reduced
dose in Group 1, 2, 3 respectively. Allwere due to Grade 3 neutropenia
or ALT increased.
Figure 1: Cumulative HBeAg Seroconversion Rate Over Time in HBeAgpositive
Patients
Conclusion: P1101 is safe for chronic HBV infection. P1101 450 μg
q2w yielded the highest HBeAg seroconversion rate. Shorter time to
HBeAg seronconversion was observed in both P1101 groups. P1101
450μg q2w is selected for a Phase3 study to confirm efficacy and
safety on HBeAg-positive patients.

StephenW

EASL 2018 FRI-328
每两周绳索干扰素α-2b安全性较高
乙型肝炎e抗原血清转换率干扰素幼稚
慢性乙型肝炎感染患者：第二阶段，开放标签，
随机，主动控制，剂量发现研究
Y.-W. Huang1，P.-J. Chen2，C.-W. Hsu3，S.-N. Lu4，M.-L. Yu5，C.-W. SU6，
W.-W. Su7，R.-N. Chien8，C.-S. Hsu9，S.-J. Hsu10，H.-C. Lai11，K.Tseng12。
1台湾台北市肝病中心综合医院医疗中心;
台湾台湾大学医学研究部;
三连楼长庚医院纪委
台北市内科医学部肝胃肠病研究所;
三雄长庚医院纪要
Hepatogastroenterology; 5高雄医科大学附属医院，
肝胆科，内科和肝炎
中心，台湾高雄;台北军区总医院6部
台北市内科医学部肝胃肠病学系，
台湾; 7长化基督教医院内科
台湾彰化医药; 8基隆长庚医院，
内科医学部肝胃病研究室，
基隆; 9台北慈济总医院消化科
和新北市内科，肝脏病学，
台湾;台湾大学附属医院运林分部10
胃肠病学与肝病学系，内科，
云林，台湾; 11中国医科大学附属第一医院
台湾内科医学院肝胃肠病学系，
台湾;台湾台北医学研究12PharmaEssentia Corp
电子邮件：[email protected]
背景和目标：Ropeginterferfer alfa-2b（P1101）是一本小说
具有较长作用持续时间的单聚乙二醇化干扰素α-2b，
允许每两周（q2w）注射具有高耐受性
由以往的研究显示。本研究旨在寻找最佳剂量
通过比较抗病毒活性和整个治疗的安全性来评估P1101
组干扰素幼稚慢性乙型肝炎病毒患者
（HBV）感染。
方法：31例乙型肝炎e抗原（HBeAg）阳性受试者
基线HBV DNA> 20,000IU / ml和31 HBeAg阴性
基线HBV DNA> 2000IU / ml的受试者被随机分配到
1：1：1比率皮下处理q2wP1101350μg（组1），
q2w P1101450μg（组2）或每周（q1w）聚乙二醇化干扰素α-2a
180微克（第3组，对照）。每位患者接受48周
治疗（TW48）和24周治疗后随访（FW24）。
结果：在HBeAg（+）受试者中，累计HBeAg血清学转换
率分别为27％（3/11），36％（4/11），11％（1/9）（p = 0.21）
到HBeAg血清转换24,24和48周（p = 0.28），在组中
1，2，3。在FW24时，HBV DNA <2,000 IU / ml为27％（3/11），
0％（0/11）和22％（2/9）（p = 0.22）乙型肝炎表面抗原
（HBsAg）<1,500IU / ml为46％（5/11），18％（2/11），11％（1/9）（p = 0.27），
抗-HBe阳性率为46％（5/11），46％（5/11），18％（2/9）（p = 0.59）
分别在1,2,3组中。在FW24的HBeAg（ - ）受试者中，HBV DNA
<2000IU / ml为10％（1/10），36％（4/11），50％（5/10）（p = 0.17）和
HBsAg <1,500IU / ml为80％（8/10），91％（10/11），90％（9/10）（p =
0.83），分别在1,2,3组中。 HBeAg（+）和（ - ）患者合并
一起，10％（2/21），5％（1/22），11％（2/19）停止治疗
由于1,2,3组分别出现不良事件（AE）。 AEs for
停药是3级心肌梗死（MI）和4级
丙氨酸氨基转移酶（ALT）在第1组中增加，多个等级
1组中1名受试者出现1例AE，2名受试者出现3级ALT升高
的第三组。MI患者有吸烟的危险因素
高脂血症。约14％（3/21），14％（3/22），11％（2/19）减少
剂量分别为1,2,3组。全部由于3级中性粒细胞减少
或ALT升高。
图1：HBeAg阳性患者累计HBeAg血清转化率随时间的变化
耐心
结论：P1101对慢性HBV感染是安全的。 P1101 450微克
q2w产生了最高的HBeAg血清转化率。更短的时间
在P1101组中观察到HBeAg血清转化。 P1101
阶段3研究选择450μgq2w以确认功效和
HBeAg阳性患者的安全性。

StephenW

对不起，发布错误.现在更正了.

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