Efficacy and Safety of Combination Therapy of Thymalfasin and Entecavir in HBeAg-positive ETV-experienced Patients
Primary Purpose
Chronic Hepatitis b
Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Thymosin Alpha1
Entecavir
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis b focused on measuring thymosin alpha, entecavir
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
Sites / Locations
- Huashan Hospital of Fudan UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
combiantion therapy group
entecavir group
Arm 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
ETV (0.5 mg orally, daily) at least for 72 weeks
Outcomes
Primary Outcome Measures
HBeAg seroconversion rate at week 72
HBeAg seroconversion rate at week 72
Secondary Outcome Measures
HBeAg seroconversion rate at week 48
HBeAg seroconversion rate at week 48
HBsAg loss at week 48
HBsAg loss at week 48
HBsAg loss at week 72
HBsAg loss at week 72
HBsAg seroconversion at week 72
HBsAg seroconversion at week 72
HBsAg seroconversion at week 48
HBsAg seroconversion at week 48
HBsAg decline during the clinical trial
HBsAg decline during the clinical trial
ALT normalization rate at week 72
ALT normalization rate at week 72
ALT normalization rate at week 48
ALT normalization rate at week 48
Rate of HBV DNA <20IU/mL at week 72
Rate of HBV DNA <20IU/mL at week 72
Rate of HBV DNA <20IU/mL at week 48
Rate of HBV DNA <20IU/mL at week 48
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03448744
Brief Title
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
2. Study Status
Record Verification Date
February 2018
Overall Recruitment Status
Unknown status
Study Start Date
October 25, 2017 (Actual)
Primary Completion Date
December 30, 2018 (Anticipated)
Study Completion Date
December 30, 2018 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Wen-hong Zhang
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis b
Keywords
thymosin alpha, entecavir
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
240 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
combiantion therapy group
Arm Type
Experimental
Arm 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
Arm Title
entecavir group
Arm Type
Placebo Comparator
Arm Description
ETV (0.5 mg orally, daily) at least for 72 weeks
Intervention Type
Drug
Intervention Name(s)
Thymosin Alpha1
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Entecavir
Intervention Description
ETV (0.5 mg orally, daily) for 72 weeks
Primary Outcome Measure Information:
Title
HBeAg seroconversion rate at week 72
Description
HBeAg seroconversion rate at week 72
Time Frame
week 72
Secondary Outcome Measure Information:
Title
HBeAg seroconversion rate at week 48
Description
HBeAg seroconversion rate at week 48
Time Frame
week 48
Title
HBsAg loss at week 48
Description
HBsAg loss at week 48
Time Frame
week 48
Title
HBsAg loss at week 72
Description
HBsAg loss at week 72
Time Frame
week 72
Title
HBsAg seroconversion at week 72
Description
HBsAg seroconversion at week 72
Time Frame
week 72
Title
HBsAg seroconversion at week 48
Description
HBsAg seroconversion at week 48
Time Frame
week 48
Title
HBsAg decline during the clinical trial
Description
HBsAg decline during the clinical trial
Time Frame
week 12, weeek 24, week 36, week 48 and week 72
Title
ALT normalization rate at week 72
Description
ALT normalization rate at week 72
Time Frame
week 72
Title
ALT normalization rate at week 48
Description
ALT normalization rate at week 48
Time Frame
week 48
Title
Rate of HBV DNA <20IU/mL at week 72
Description
Rate of HBV DNA <20IU/mL at week 72
Time Frame
week 72
Title
Rate of HBV DNA <20IU/mL at week 48
Description
Rate of HBV DNA <20IU/mL at week 48
Time Frame
week 48
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yiqi Yu, MD
Phone
+86-21-52888123
Email
yyq19890619@126.com
First Name & Middle Initial & Last Name or Official Title & Degree
Ying Yue, MD
Phone
+86-21-52888123
Email
ye_zicissy@sohu.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Wenhong Zhang, Ph.D
Organizational Affiliation
Department of Infectious Diseases, Huashan Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Huashan Hospital of Fudan University
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200040
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wenhong Zhang, PhD,MD
Phone
+86 21 52889999
Ext
8123
Email
zhangwenhong@fudan.edu.cn
12. IPD Sharing Statement
Plan to Share IPD
No
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Efficacy and Safety of Combination Therapy of Thymalfasin and Entecavir in HBeAg-positive ETV-experienced Patients
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