Clinical trial NCT03448744: Efficacy and Safety of Combination Therapy of Thymalfasin and Entecavir in HBeAg-positive ETV-experienced Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis b
Keywords: thymosin alpha
entecavir
Lead sponsor: Huashan Hospital
Sponsor class: OTHER
First posted: 2018-02-28
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: HBeAg seroconversion rate at week 72
timeFrame: week 72
Secondary outcomes:
measure: HBeAg seroconversion rate at week 48
timeFrame: week 48
measure: HBsAg loss at week 48
timeFrame: week 48
measure: HBsAg loss at week 72
timeFrame: week 72
measure: HBsAg seroconversion at week 72
timeFrame: week 72
measure: HBsAg seroconversion at week 48
timeFrame: week 48
measure: HBsAg decline during the clinical trial
timeFrame: week 12, weeek 24, week 36, week 48 and week 72
measure: ALT normalization rate at week 72
timeFrame: week 72
measure: ALT normalization rate at week 48
timeFrame: week 48
measure: Rate of HBV DNA <20IU/mL at week 72
timeFrame: week 72
measure: Rate of HBV DNA <20IU/mL at week 48
timeFrame: week 48
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Huashan Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Department of Infectious Diseases, Huashan Hospital
name: Wenhong Zhang, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: