Evaluate the Safety, Tolerability, and Antiviral Activity of GLS4 With Ritonavir in Patients With Chronic HBV Infection

Evaluate the Safety, Tolerability, and Antiviral Activity of GLS4 With Ritonavir in Combination With Entecavir in Comparison With Entecavir Alone in Patients With Chronic HBV Who Are HBeAg Positive

The experiment is divided into two parts: Part 1 and Part 2.Part 1 was the initial treatment patient and Part 2 was the treated patient.

Study Overview

• Status: Completed
• Conditions: Chronic HBV Infection
• Intervention / Treatment: Drug: GLS4; Drug: RTV; Drug: ETV

Detailed Description

About 125 subjects were planned to be included and assigned to the experimental group and the control group according to 4:1.At the same time, a liver biopsy group was set up in each part of the population to receive liver biopsy during the screening period and 48 weeks after completion of drug administration, which was used to detect HBV DNA, cccDNA, HBsAg, and evaluate the degree of liver inflammation and fibrosis.

• Study Type: Interventional
• Enrollment (Actual): 250
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100069
      • Beijing youan hospital，capital medical university
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
    • Beijing, Beijing, China, 100020
      • Beijing Ditan Hospital Affiliated to Capital Medical University
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • The Second Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China, 400042
      • The First Affiliated Hospital of Chongqing Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Mengchao Hepatobiliary Hospital of Fujian Medical University
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • The First Hospital of Lanzhou University
  • Guangdong
    • Guangzhou, Guangdong, China, 510630
      • The Third Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510060
      • Guangzhou Eighth People's Hospital
  • Guangxi
    • Nanning, Guangxi, China, 530021
      • The First Affiliated Hospital of Guangxi Medical University
  • Guizhou
    • Guiyang, Guizhou, China, 550001
      • Affiliated Hospital of Guizhou Medical University
    • Zunyi, Guizhou, China, 563000
      • Affiliated Hospital of Zunyi Medical College
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The Fourth Affiliated Hospital of Harbin Medical University
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan Provincial People's Hospital
  • Hubei
    • Wuhan, Hubei, China, 430010
      • The Central Hospital of Wuhan
    • Wuhan, Hubei, China, 430022
      • Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University Science & Technology
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital, Central South University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210003
      • The Second Hospital of Nanjing
    • Nanjing, Jiangsu, China, 210008
      • Nanjing Gulou Hospital
    • Nanjing, Jiangsu, China, 210002
      • The People's Liberation Army No.81 Hospital
    • Zhenjiang, Jiangsu, China, 212004
      • The Third People's Hospital of Zhenjiang
  • Jilin
    • Chang chun, Jilin, China, 130012
      • The First Hospital of Jilin University
    • Changchun, Jilin, China, 130041
      • The Second Hospital of Jilin University
  • Shandong
    • Qingdao, Shandong, China, 266011
      • Qingdao Municipal Hospital
  • Shanghai
    • Shanghai, Shanghai, China, 200020
      • Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai, China, 200062
      • Shanghai Putuo District Central Hospital
    • Shanghai, Shanghai, China, 201500
      • Shanghai Public Health Clinical Center
    • Shanghai, Shanghai, China, 200040
      • Huashan Sub-Hospital of Fudan University
  • Shanxi
    • Xi'an, Shanxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University
    • Xi'an, Shanxi, China, 710038
      • The Second Affiliated Hospital of Air Force Medical University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
    • Chengdu, Sichuan, China, 610072
      • Sichuan Provincial People's Hospital
  • Tianjing
    • Tianjing, Tianjing, China, 300170
      • Tianjin Third Central Hospital
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Chronic HBV infection population
• HBeAg positive
• HBsAg≥250 IU/mL
• No cirrhosis

Exclusion Criteria:

• AST>5×ULN
• Platelet count less than 90E+09/L
• TBil>1.5×ULN
• albumin<35 g/L
• INR>1.5
• AFP>50 ng/mL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Combination group; Subjects will receive 96 weeks of GLS4+RTV+ETV.	Drug: GLS4; Administered GLS4 120 mg orally three times daily in fed state; Other Names: Morphothiadine Mesilate Capsules; Drug: RTV; Administered RTV 100 mg orally three times daily in fed state; Other Names: Ritonavir tablet; Drug: ETV; Administered orally ETV 0.5 mg once daily in fasted state; Other Names: Entecavir table
Active Comparator: Entecavir monotherapy; Subjects received 96 weeks of entecavir treatment	Drug: ETV; Administered orally ETV 0.5 mg once daily in fasted state; Other Names: Entecavir table

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The value of serum HBsAg decreased from baseline	The value of serum HBsAg at 48 weeks of treatment was lowered compared with baseline.	48 weeks after dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The value of serum HBeAg decreased from baseline	The value of serum HBeAg at 48 weeks of treatment was lowered compared with baseline.	48 weeks after dosing
The value of HBV DNA decreased from baseline	The value of HBV DNA at 48 weeks of treatment was lowered compared with baseline.	48 weeks after dosing
The value of serum HBsAg decreased from baseline	The value of serum HBsAg at 24 weeks of treatment was lowered compared with baseline.	24 weeks after dosing
The value of serum HBeAg decreased from baseline	The value of serum HBeAg at 24 weeks of treatment was lowered compared with baseline.	24 weeks after dosing
The value of HBV DNA decreased from baseline	The value of HBV DNA at 24 weeks of treatment was lowered compared with baseline.	24 weeks after dosing

Collaborators and Investigators

• Sponsor: Sunshine Lake Pharma Co., Ltd.
• Investigators: Principal Investigator: junqi Niu, Doctor, The First Hospital of Jilin University

Study record dates

Study Major Dates

• Study Start (Actual): February 28, 2019
• Primary Completion (Actual): June 23, 2022
• Study Completion (Actual): September 14, 2023

Study Registration Dates

• First Submitted: October 28, 2019
• First Submitted That Met QC Criteria: October 30, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 20, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Chronic HBeAg positive HBV Infection
• Additional Relevant MeSH Terms: Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Entecavir; Ritonavir
• Other Study ID Numbers: PCD-DGLS4-18-002

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