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
Trial Snapshot
- Phase
- Phase 4
- Sponsor
- Enrollment
- 240
- Locations
- 1
- Primary Endpoint
- HBeAg seroconversion rate at week 72
Study Overview
Brief Summary
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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Investigator)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
combiantion therapy group
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
Intervention: Thymosin Alpha1 (Drug)
combiantion therapy group
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
Intervention: Entecavir (Drug)
entecavir group
ETV (0.5 mg orally, daily) at least for 72 weeks
Intervention: Entecavir (Drug)
Outcomes
Primary Outcomes
HBeAg seroconversion rate at week 72
Time Frame: week 72
HBeAg seroconversion rate at week 72
Secondary Outcomes
- Rate of HBV DNA <20IU/mL at week 48(week 48)
- HBsAg loss at week 48(week 48)
- HBsAg seroconversion at week 72(week 72)
- ALT normalization rate at week 72(week 72)
- ALT normalization rate at week 48(week 48)
- Rate of HBV DNA <20IU/mL at week 72(week 72)
- HBeAg seroconversion rate at week 48(week 48)
- HBsAg loss at week 72(week 72)
- HBsAg seroconversion at week 48(week 48)
- HBsAg decline during the clinical trial(week 12, weeek 24, week 36, week 48 and week 72)
Investigators
Wen-hong Zhang
Professor
Huashan Hospital