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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Chronic Hepatitis b

Intervention / Treatment
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* Drug: Thymosin Alpha1
* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: combiantion therapy group<br>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 | Drug: Thymosin Alpha1<br>* Thymosin Alpha1 (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<br>Drug: Entecavir<br>* ETV (0.5 mg orally, daily) for 72 weeks<br>|
| Placebo Comparator: entecavir group<br>ETV (0.5 mg orally, daily) at least for 72 weeks | Drug: Entecavir<br>* ETV (0.5 mg orally, daily) for 72 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBeAg seroconversion rate at week 72 | HBeAg seroconversion rate at week 72 | week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBeAg seroconversion rate at week 48 | HBeAg seroconversion rate at week 48 | week 48 | 
| HBsAg loss at week 48 | HBsAg loss at week 48 | week 48 | 
| HBsAg loss at week 72 | HBsAg loss at week 72 | week 72 | 
| HBsAg seroconversion at week 72 | HBsAg seroconversion at week 72 | week 72 | 
| HBsAg seroconversion at week 48 | HBsAg seroconversion at week 48 | week 48 | 
| HBsAg decline during the clinical trial | HBsAg decline during the clinical trial | week 12, weeek 24, week 36, week 48 and week 72 | 
| ALT normalization rate at week 72 | ALT normalization rate at week 72 | week 72 | 
| ALT normalization rate at week 48 | ALT normalization rate at week 48 | week 48 | 
| Rate of HBV DNA <20IU/mL at week 72 | Rate of HBV DNA <20IU/mL at week 72 | week 72 | 
| Rate of HBV DNA <20IU/mL at week 48 | Rate of HBV DNA <20IU/mL at week 48 | week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thymosin alpha, entecavir