SWITCH OR ADD PEGYLATED-INTERFERON IN CHRONIC HEPATITIS B PATIENTS ON LONG TERM NUCLEOS(T)IDE THERAPY (SWAP TRIAL)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 254
- 试验地点
- 4
- 主要终点
- Reduction in quantitative HBsAg>1 log
研究概览
简要总结
Patients with Chronic Hepatitis B on long term oral antiviral therapy have to continue treatment indefinitely unless they achieve HBeAg seroconversion or HBsAg seroclearance, when therapy can be stopped. While HBeAg seroconversion is a more achievable endpoint, only 20-25% of patients develop this after one year of oral antiviral therapy. HBsAg seroclearance is universally infrequent. Strategies to improve these endpoints such as combination oral antiviral therapy have not been generally successful and recently studies have examined the possibility of switching or adding peginterferon therapy. However these have not been tested adequately in the group of patients that have been on long term oral antiviral therapy. Consequently this study was conceived to evaluate whether switching or adding peginterferon compared to continuing oral antiviral therapy are more efficacious strategies. HBeAg positive and HBeAg negative patients (n=310)will be randomised to continue oral antiviral therapy, switch or add pegylated interferon for 48 weeks in a ratio of 1:2:2 respectively. The study endpoints are HBsAg seroclearance, reduction of qHBsAg >1 log, qHBsAg<200 IU/ml, HBeAg loss and seroconversion, and HBV DNA suppression, all at week 72.
详细描述
- HYPOTHESIS AND OBJECTIVES PEG-IFN as an immunomodulatory agent could potentiate the antiviral efficacy of patients on long term nucleos(t)ide analogue therapy and improve early indicators of efficacy, HBeAg loss and reduction in qHBsAg. This study will also test whether add-on compared to switch PEG-IFN is superior, if at all.
- STUDY DESIGN This is a randomized, open-label, active-controlled study to evaluate safety and the efficacy of HBeAg loss or reduction in qHBsAg >1 log in nucleos(t)ide analogue treated chronic hepatitis B subjects who will be treated with add on PEG (A), switch to PEG (B) or continued nucleos(t)ide analogue (C) for 48 weeks. Patients randomized to Arm B will have a one-month overlap period when switching from existing NA to PEG monotherapy. This is to prevent viral rebound during the switch. Patients will be randomized in a 2:2:1 ratio to one of the 3 treatment arms A, B, and C. Arms A and B are experimental arms. Arm C is the control arm.
- STUDY POPULATION Approximately 255 subjects will be enrolled into this study.
3.1 Inclusion Criteria
For entry into this study, the following inclusion criteria must be met:
- Age 21 - 70 years old (inclusive)
- Male or female subjects with chronic hepatitis B (ie. presence of positive HBsAg or HBV DNA for at least 6 months.
- On any NA (lamivudine, adefovir, entecavir or tenofovir) for ≥ 1 year
- HBV DNA undetected at screening
- Patient has agreed not to take any other investigational drug or systemic anti-viral, cytotoxic, corticosteroid, immunomodulatory agents or Chinese traditional remedies unless clinically indicated.
- Patient is able to give written consent prior to study start and to comply with the study requirements.
- Women of childbearing age must have a negative urine (ß-HCG) pregnancy test taken within 14 days of starting therapy
3.2 Exclusion Criteria
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Between 21 and 70 years old.
- •Documented to be HBsAg positive for ≥ 6 months.
- •On any nucleos(t)ide analogue (lamivudine, adefovir, entecavir or tenofovir)for ≥ 1 year
- •HBV DNA undetectable by RT PCR at screening
- •Patient has agreed not to take any other investigational drug or systemic anti-viral, cytotoxic, corticosteroid, immunomodulatory agents or Chinese traditional remedies unless clinically indicated.
- •Patient is able to give written consent prior to study start and to comply with the study requirements.
- •Women of childbearing age must have a negative serum (ß-HCG) pregnancy test taken with 14 days of starting therapy
排除标准
- •Evidence of decompensated liver disease or hepatocellular carcinoma.
- •Have any of the following laboratory tests within 4 weeks of study entry:
- •HIV antibody or HCV antibody or HDV antibody positivity
- •Absolute neutrophil count < 1.5 X 109/l or platelets < 90 x 109/l or hemoglobin < 13 g/dL for men or 12g/dL for women
- •serum albumin <35 g/l or serum bilirubin > 30 mg/l
- •creatinine > 1.5 times upper limit of normal
- •prothrombin time > 1.5 times control, uncorrected by Vitamin K therapy.
- •Any interferon, Immunomodulators, systemic cytotoxic agents, or systemic corticosteroids within 6 months before trial entry.
- •Prolonged exposure to known hepatotoxins such as alcohol or drugs.
- •History of clinically relevant psychiatric disease, seizures, central nervous system dysfunction, severe pre-existing cardiac, renal, hematological disease or medical illness that in the investigator's opinion might interfere with therapy.
- •Malignant disease within 5 years of trial entry.
- •Women who are pregnant and who are not practicing adequate birth control measures, or who are lactating
研究组 & 干预措施
Continued oral nucleos(t)ide therapy
Patients assigned to this arm will continue their nucleos(t) analogue
干预措施: Nucleos(t)ide analogue therapy (Drug)
Add on peg-interferon
Patients assigned to this arm will continue their existing nucleos(t)ide therapy and also be assigned peg-interferon alpha 2b 1.5mcg/kg sc weekly
干预措施: peg-interferon alpha 2b, 1.5mcg/kg s/c given weekly (Drug)
Add on peg-interferon
Patients assigned to this arm will continue their existing nucleos(t)ide therapy and also be assigned peg-interferon alpha 2b 1.5mcg/kg sc weekly
干预措施: Nucleos(t)ide analogue therapy (Drug)
switch to peg-interferon
Patients assigned to this arm will stop their existing nucleos(t)ide therapy after one month overlap after starting peg-interferon alpha 2b 1.5mcg/kg sc weekly
干预措施: peg-interferon alpha 2b, 1.5mcg/kg s/c given weekly (Drug)
结局指标
主要结局
Reduction in quantitative HBsAg>1 log
时间窗: Week 72
HBeAg loss
时间窗: week 72
次要结局
- HBsAg <200 IU/ml(week 72)
- undetectable HBV DNA(week 72)
- HBsAg seroclearance(week 72)
- HBeAg seroconversion(week 72)
研究者
Seng Gee Lim
Director of Hepatology, Dept of Gastroenterology and Hepatology
National University Health System, Singapore