Efficacy and Safety of Entecavir Maleate Tablets in Chinese Patients With Hepatitis B

The purpose of this study is to evaluate the safety and efficacy of Entecavir maleate tablets in Chinese patients with hepatitis B

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Entecavir maleate tablets; Drug: blank Baraclude tablets; Drug: Blank maleate entecavir tablets; Drug: Baraclude tablets

• Study Type: Interventional
• Enrollment (Actual): 287
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Department of Infectious Diseases,Peking University First Hospital
    • Beijing, Beijing, China, 100054
      • Beijing You An Hospital，Capital Medical University
  • Chongqing
    • Chongqing, Chongqing, China, 400038
      • The First Affiliated Hospital Of The Third Mililary Medical University
  • Hubei
    • Wuhan, Hubei, China, 430030
      • Tongji Medical College of Hust Tongji Medical College Huazhong University of Science and Technology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • The First Affiliated Hospital of Nanjing medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Shanghai Jiaotong University Affiliated Ruijin Hospital
  • Sichuan
    • Chongqing, Sichuan, China, 400010
      • West China Hospital of Sichuan University
    • Chongqing, Sichuan, China, 400010
      • The Second Affiliated Hospital of Chongqing Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The First Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subjects diagnosed of HBeAg positive or negative chronic hepatitis B
2. Aged 18 to 70 years old，male or female
3. Patients with previously HBsAg-positive, HBeAg-positive for 24 weeks, HBV-DNA> 105copies/ml. HBeAg-negative for 24 weeks or more, HBV-DNA> 105 copies/ml.
4. 1.3 times the upper normal limit (1.3 × ULN) ≤ alanine aminotransferase (ALT) ≤ 10 × ULN.
5. Total serum bilirubin (TBIL) ≤ 2.5 × ULN.
6. Prothrombin activity (PTA) ≥ 60% or prothrombin time prolonged than normal ≤ 3 seconds).
7. WBC ≥ 3.5 × 109 / L, PLT ≥ 70 × 109 / L, serum albumin (ALB)≥ 35 g / L.
8. Creatinine (Cr) ≤ 1.5 × ULN.
9. If patients take intermittently with interferon, nucleoside (acid) analogues, α1 thymosin before enrollment with 24 weeks, the time is no more than 12 weeks.
10. Patients signed an informed consent form and compliance was good.

Exclusion Criteria:

1. Patients were infected with other viruses as HAV, HCV, HDV, HEV, CMV, EBV, HIV etc.
2. Patients with cirrhosis or liver cancer.
3. Patients have participated in another therapeutic clinical trial in 3 months.
4. Granulocyte count <1.5 × 109 / L, hemoglobin (HB)<100g / L, sera alpha-fetoprotein(AFP)> 100μg / L, patients' B ultrasonography pointed space-occupying lesions.
5. Patients with severe heart, kidney, endocrine hematopoietic system and neuropsychiatric diseases.
6. Patients with metabolic or autoimmune diseases such as systemic lupus erythematosus.
7. Pregnant woman, lactating women or those who wre allergic for study drug.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: HBeAg positive group; Entecavir maleate tablets (1) + blank Baraclude tablets (1),once a day Empty stomach (at least 2 hours after a meal or fasting), treatment for 48 weeks, then enter the open-label trial extended to 240 weeks . Blank maleate entecavir tablets (1) + Baraclude tablets (1),once a day Empty stomach (at least 2 hours after a meal or fasting), treatment for 48 weeks, then enter the open-label trial extended to 240 weeks .	Drug: Entecavir maleate tablets; Drug: blank Baraclude tablets; Drug: Blank maleate entecavir tablets; Drug: Baraclude tablets
Other: HBeAg-negative group; Entecavir maleate tablets (1) + blank Baraclude tablets (1),once a day Empty stomach (at least 2 hours after a meal or fasting), treatment for 48 weeks, then enter the open-label trial extended to 240 weeks . Blank maleate entecavir tablets (1) + Baraclude tablets (1),once a day Empty stomach (at least 2 hours after a meal or fasting), treatment for 48 weeks, then enter the open-label trial extended to 240 weeks .	Drug: Entecavir maleate tablets; Drug: blank Baraclude tablets; Drug: Blank maleate entecavir tablets; Drug: Baraclude tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Compared with baseline, decline of serum HBV-DNA in the value	5 years

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Investigators: Principal Investigator: Yu Yan yan, doctor, Department of Infectious Diseases,Peking University First Hospital; Principal Investigator: Shi Guang feng, doctor, Huashan Hospital; Principal Investigator: Xie Qing, doctor, Shanghai Jiaotong University Affiliated Ruijin Hospital; Principal Investigator: Tang Hong, doctor, West China Hospital; Principal Investigator: Zhang Da zhi, doctor, The Second Affiliated Hospital of Chongqing Medical University; Principal Investigator: Mao Qing, doctor, The First Affiliated Hospital Of The Third Mililary Medical University; Principal Investigator: Ning Qin, doctor, Tongji Medical College of Hust Tongji Medical College Huazhong University of Science and Technology; Principal Investigator: Li Jun, doctor, The First Affiliated Hospital with Nanjing Medical University; Principal Investigator: Sheng Ji fang, doctor, Zhejiang University; Principal Investigator: Cheng Xin fang, doctor, Beijing You An Hospital，Capital Medical University

Publications and helpful links

General Publications

• Xu JH, Wang S, Zhang DZ, Yu YY, Si CW, Zeng Z, Xu ZN, Li J, Mao Q, Tang H, Sheng JF, Chen XY, Ning Q, Shi GF, Xie Q, Zhang XQ, Dai J. One hundred and ninety-two weeks treatment of entecavir maleate for Chinese chronic hepatitis B predominantly genotyped B or C. World J Clin Cases. 2022 Oct 6;10(28):10085-10096. doi: 10.12998/wjcc.v10.i28.10085.
• Xu JH, Wang S, Xu ZN, Yu YY, Si CW, Zeng Z, Li J, Mao Q, Zhang DZ, Tang H, Sheng JF, Chen XY, Ning Q, Shi GF, Xie Q, Zhang XQ, Dai J. Entecavir maleate versus entecavir in Chinese chronic hepatitis B predominantly genotype B or C: Results at week 144. J Viral Hepat. 2017 Oct;24(10):877-884. doi: 10.1111/jvh.12710. Epub 2017 Aug 11.
• Li N, Xu JH, Yu M, Wang S, Si CW, Yu YY. Relationship between virological response and FIB-4 index in chronic hepatitis B patients with entecavir therapy. World J Gastroenterol. 2015 Nov 21;21(43):12421-9. doi: 10.3748/wjg.v21.i43.12421.

Study record dates

Study Major Dates

• Study Start: October 1, 2008
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: August 13, 2013
• First Submitted That Met QC Criteria: August 19, 2013
• First Posted (Estimate): August 20, 2013

Study Record Updates

• Last Update Posted (Actual): December 29, 2017
• Last Update Submitted That Met QC Criteria: December 27, 2017
• Last Verified: August 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Entecavir; Maleic acid
• Other Study ID Numbers: CTTQ805-4