Efficacy and Safety of Combination Therapy of Thymalfasin and Entecavir in HBeAg-positive ETV-experienced Patients

A Multicenter, Randomized, Open-label Control Study to Evaluate Efficacy and Safety of Combination Therapy of Thymalfasin and Entecavir in HBeAg-positive ETV-experienced Patients

This is a multicenter, randomized, open-label control trial of two arms conducted at 10 centres in China.The aim was to investigate whether sequential combination therapy with Thymosin alpha 1 and entecavir is superior to continuous ETV monotherapy in HBeAg-positive chronic hepatitis B patients with previous long-term entecavir therapy (≥ 2 years), and to select the optimal patients who may benefit from sequential combination therapy.

To investigate whether sequential combination therapy with Thymosin alpha 1 and entecavir is superior to continuous ETV monotherapy in HBeAg-positive chronic hepatitis B patients with previous long-term entecavir therapy (≥ 1 years), and to select the optimal patients who may benefit from sequential combination therapy.

Inclusion Criteria:

• HBsAg positive and anti-HBs negative for more than 6 months
• Being currently treated with ETV ≥1 years
• HBeAg positivity and HBV DNA <60IU/mL with HBsAg <1500IU/mL and HBeAg <200S/CO at screening
• ALT ≤5*ULN and total bilirubin ≤2*ULN
• Age ≥ 18 yrs but ≤ 55 yrs
• Written informed consent

Exclusion Criteria:

• Patients who have contraindications for Thymosin alpha 1 in accordance with the approved summary of product characteristics
• Patients with ALT > 5 x ULN or total bilirubin >2*ULN
• Patients with evidence of hepatocellular carcinoma at screening
• Patients with Child-Pugh score ≥7 or had a history of hepatic encephalopathy or esophageal pile or ascites
• Patients with serological evidence of co-infection with hepatitis A virus, hepatitis C, human immunodeficiency virus or hepatitis D virus
• Patients with a history of excessive drinking: male >40g/d,female >40g/d
• Pregnant or breast-feeding women
• A history of liver transplantation or planned for liver transplantation
• Patients of autoimmune disease
• Patients with other diseases combined
• Patients with creatinine >1.5*ULN
• Investigator considered not proper for participating the trial
• Patients with other maliginant tumor