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

Wen-hong Zhang

Status and phase: Unknown; Phase 4

Conditions: Chronic Hepatitis b

Treatments: Drug: Thymosin Alpha1; Drug: Entecavir

Study type: Interventional

Funder types: Other

Identifiers

NCT03448744

KY2016-219

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 240 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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240 participants in 2 patient groups, including a placebo group

combiantion therapy group

Experimental group

Description:

thymosin alpha 1 (1.6 mg subcutaneously injection twice a week) plus ETV (0.5 mg orally, daily) for 24 weeks, and followed by continuous ETV for at least 48 weeks

Treatment:

Drug: Entecavir

Drug: Thymosin Alpha1

entecavir group

Placebo Comparator group

Description:

ETV (0.5 mg orally, daily) at least for 72 weeks

Treatment:

Drug: Entecavir