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.

Study Overview

• Status: Unknown
• Conditions: Chronic Hepatitis b
• Intervention / Treatment: Drug: Thymosin Alpha1; Drug: Entecavir

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 Type: Interventional
• Enrollment (Anticipated): 240
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yiqi Yu, MD; Phone Number: +86-21-52888123; Email: yyq19890619@126.com
• Study Contact Backup: Name: Ying Yue, MD; Phone Number: +86-21-52888123; Email: ye_zicissy@sohu.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Recruiting
      • Huashan Hospital of Fudan University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: Thymosin Alpha1; 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; Drug: Entecavir; ETV (0.5 mg orally, daily) for 72 weeks
Placebo Comparator: entecavir group; ETV (0.5 mg orally, daily) at least for 72 weeks	Drug: Entecavir; ETV (0.5 mg orally, daily) for 72 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Wen-hong Zhang
• Investigators: Principal Investigator: Wenhong Zhang, Ph.D, Department of Infectious Diseases, Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2017
• Primary Completion (Anticipated): December 30, 2018
• Study Completion (Anticipated): December 30, 2018

Study Registration Dates

• First Submitted: February 22, 2018
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (Actual): February 28, 2018

Study Record Updates

• Last Update Posted (Actual): February 28, 2018
• Last Update Submitted That Met QC Criteria: February 22, 2018
• Last Verified: February 1, 2018

More Information

Terms related to this study

• Keywords: entecavir; thymosin alpha
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Immunologic Factors; Adjuvants, Immunologic; Entecavir; Thymalfasin
• Other Study ID Numbers: KY2016-219

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No