An Open-Label, Pilot, Randomized, Multi-Center Study to Compare Efficacy and Safety of Tenofovir Monotherapy Alone With Tenofovir Monotherapy Followed by Concurrent Combination of Pegylated Interferon-Alpha-2b and Tenofovir or Tenofovir Monotherapy Followed by Sequential Therapy of Pegylated Interferon-Alpha-2b and Tenofovir in HBeAG-Positive Chronic Hepatitis B Patients With Raised ALT.
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 主要终点
- Number of participants who responded to treatment
研究概览
简要总结
This study will compare monotherapy with tenofovir to sequential therapy with pegylated interferon alpha-2b (pegIFN-2b) followed by tenofovir, and to combination therapy with pegIFN-2b + tenofovir, in participants with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B and elevated alanine aminotransferase (ALT). All enrolled participants will be be administered tenofovir alone for 8 weeks and then will be randomly assigned to 1 of the 3 treatment arms.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic hepatitis B (hepatitis B surface antigen [HBsAg]-positive for >6 months or evidence of chronic hepatitis B in liver biopsy)
- •Elevated serum ALT level
- •Liver biopsy or a non-invasive investigation within 12 months prior to randomization with Chronic Hepatitis B
- •Treatment naïve or history of interferon for not more than 1 month, taken at least 6 months before enrollment
- •Compensated liver disease
排除标准
- •Known hypersensitivity to tenofovir, interferon alpha-2b, and/or any other component of the study products
- •Co-infection with hepatitis C virus (HCV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
- •Need for prolonged or frequent use of systemic acyclovir or famciclovir
- •Previously received lamivudine or an investigational anti-hepatitis B virus (HBV) nucleoside or nucleotide analog and were resistant to these drugs
- •History of variceal bleeding or other GI bleeding due to portal hypertension, hepatic encephalopathy, spontaneous bacterial peritonitis, Grade III and IV esophageal varices unless banded or other clinical signs of hepatic decompensation
- •History of hepatocellular carcinoma (HCC) or findings suggestive of possible HCC
- •Need for potentially hepatotoxic drugs (e.g. dapsone, erythromycin, fluconazole, ketoconazole, rifampin, and anti-tuberculosis regimens) or nephrotoxic drugs (e.g. frequent nonsteroidal anti-inflammatories, aminoglycosides, amphotericin B, and foscarnet)
- •One or more additional known primary or secondary causes of liver disease, other than hepatitis B
- •History of clinical pancreatitis
- •Pregnant or breastfeeding
- •Female participants of childbearing potential and male participants must be willing to use acceptable method of birth control.
- •Medical condition that requires frequent or prolonged use of systemic corticosteroids
- •Use of warfarin or other anticoagulants during 30 days prior to screening or if expected to be needed during the study period
研究组 & 干预措施
Tenofovir Monotherapy
Tenofovir 300 mg tablet, orally (PO) once daily for 8 weeks, then Tenofovir 300 mg tablet, PO, once daily for an additional 96 weeks (total treatment duration 104 weeks)
干预措施: Tenofovir (Drug)
PegIFN-2b/Tenofovir Sequential Therapy
Tenofovir 300 mg tablet, PO, once daily for 8 weeks, then PegIFN-2b, 1.5 mcg/kg subcutaneously (SC), once weekly, for 24 weeks, then Tenofovir 300 mg tablet, PO, once daily for 72 weeks (total treatment duration 104 weeks)
干预措施: Tenofovir (Drug)
PegIFN-2b/Tenofovir Sequential Therapy
Tenofovir 300 mg tablet, PO, once daily for 8 weeks, then PegIFN-2b, 1.5 mcg/kg subcutaneously (SC), once weekly, for 24 weeks, then Tenofovir 300 mg tablet, PO, once daily for 72 weeks (total treatment duration 104 weeks)
干预措施: Pegylated interferon alpha-2b (Biological)
Peg-IFN-2b + Tenofovir Combination Therapy
Tenofovir 300 mg tablet, PO once daily for 8 weeks, then pegIFN-2b, 1.5 mcg/kg SC once weekly and tenofovir 300 mg tablet, PO, once daily for 24 weeks, and then tenofovir 300 mg tablet, PO, once daily for 72 weeks (total treatment duration 104 weeks)
干预措施: Tenofovir (Drug)
Peg-IFN-2b + Tenofovir Combination Therapy
Tenofovir 300 mg tablet, PO once daily for 8 weeks, then pegIFN-2b, 1.5 mcg/kg SC once weekly and tenofovir 300 mg tablet, PO, once daily for 24 weeks, and then tenofovir 300 mg tablet, PO, once daily for 72 weeks (total treatment duration 104 weeks)
干预措施: Pegylated interferon alpha-2b (Biological)
结局指标
主要结局
Number of participants who responded to treatment
时间窗: Week 128
Number of participants experiencing adverse events (AEs)
时间窗: Up to 128 weeks
Number of participants discontinuing study therapy due to AEs
时间窗: Up to 104 weeks
次要结局
未报告次要终点