Study on the Tolerability, Pharmacodynamics and Pharmacokinetics of GST-HG141 Tablets

NCT04868981 | Completed Phase 1

• 1 other identifier: GST-HG141-21-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To Evaluate the Tolerability, Pharmacodynamics and Pharmacokinetics of GST-HG141 Tablets in Multiple-center, Randomized, Double-blind, Placebo-controlled Multiple-dose, Multiple-administration Study in Patients With Chronic Hepatitis B (CHB)

Conditions

Hepatitis B

Outcome Measures

Primary Outcomes (5)

• Number of patients with chronic HBV infection with treatment-related adverse events and laboratory abnormalities.

  Symptoms and physical examination, clinical laboratory examination, vital signs，12 lead ECG and adrenal ultrasounds were collected and assessed by CTCAE v5.0.

  Up to 33 days

• Cmax of GST-HG141

  Plasma samples were collected at different points for pharmacokinetic analysis

  Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.

• AUC of GST-HG141

  Plasma samples were collected at different points for pharmacokinetic analysis

  Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.

• t1/2 of GST-HG141

  Plasma samples were collected at different points for pharmacokinetic analysis

  Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.

• Cl/F of GST-HG141

  Plasma samples were collected at different points for pharmacokinetic analysis

  Measured on -0.5, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12hours on Day1; -0.5 hours on Day 8, Day 15, Day22 and Day 27 for trough concentration; -0.5, 0.5 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72 hours on Day 28.

Secondary Outcomes (4)

• The value of serum HBV DNA decreased from baseline

  Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33

• The value of serum HBV pgRNA decreased from baseline

  Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33

• The value of serum HBsAg decreased from baseline

  Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33

• The value of serum HBeAg decreased from baseline

  Plasma samples were collected before administation on the morning of day 1 and day 15 and at any time on day 29 and day 33

Study Arms (2)

GST-HG141

EXPERIMENTAL

GST-HG141 tablets at varying dosages by mouth for 28 days

Drug: GST-HG141 tablets

Matching Placebo for GST-HG141

PLACEBO COMPARATOR

Placebos for GST-HG141 tablets at varying dosages by mouth for 28 days

Drug: Matching Placebos for GST-HG141 tablets

Interventions

GST-HG141 tablets DRUG

Administrate GST-HG141 tablets orally in fed state twice daily at 25 mg or 50mg or 100 mg doses

GST-HG141

Matching Placebos for GST-HG141 tablets DRUG

Administrate the placebos for GST-HG141 tablets orally in fed state twice daily at 25 mg or 50mg or 100 mg doses

Matching Placebo for GST-HG141

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Sign the informed consent before the study and fully understand the content and process of the study as well as the possible adverse drug reactions;
• Be able to complete the study in accordance with protocol requirements;
• Subjects (including partners) are willing to take effective contraceptive measures from completion of screening to 6 months after the last Administration;
• Ages ranged from 18 to 70 years old (including 18 and 70 years old);
• Male subjects weighing no less than 45 kg, and female subjects weighing no less than 40 kg. \[Body mass index (BMI) = body weight (kg) / height 2 (m\^2)\], body mass index is in the range of 18 \~ 32 kg / m\^2 (including critical value);
• Patients with HBsAg-positive for at least 6 months (based on outpatient/inpatient medical records or laboratory report; or with IgM HBcAb-negative and HBsAg-positive when screening;
• Patients without interferon/nucleoside analogue treatment when screening, or interferon treatment was stopped more than 1 year ago, and nucleoside analogue treatment was stopped more than 6 months ago.
• For HBeAg-positive patients, HBV DNA ≥ 2×10\^5 IU/mL; For HBeAg-negative patients, HBV DNA ≥ 2×10\^4 IU/mL;
• Patients with Serum ALT less than 5×ULN when screening.

You may not qualify if:

• Patients with suspected allergy to any component of the study drug or allergic constitution (multiple drug and food allergy)；
• Patients who had major trauma or Large surgical operation within 3 months before screening or are planning to take surgical treatment during the study ;
• Patients who had blood donation or massive blood loss (≥400 mL), or had a blood transfusion within 3 months before screening; or had blood donation or massive blood loss (≥200 mL) within 1 months before screening;
• Patients with smoking more than 5 cigarettes per day within 3 months before the study or heavy drinking within 4 weeks before screening (drinking more than 14 units of alcohol per week: 1 unit = 285 mL of beer, or 25 mL of spirits, or 100 mL of wine)；
• Patients who had used immunosuppressants, immunomodulators (thymosin) and cytotoxic drugs within 6 months before dosing, or had received live attenuated vaccine within 1 month before screening;
• Patients who used immunosuppressants, immunomodulators (thymosin) and cytotoxic drugs within 6 months before dosing, or who had received live attenuated vaccine within 1 month before screening;
• Patients with clinically significant acute or chronic liver disease caused by non HBV infection (fatty liver disease is ruled out or recruited by researcher);
• Patients with history of liver cirrhosis or progressive liver fibrosis (e.g., liver histopathology reported liver cirrhosis or endoscopy indicated esophageal and gastric varices);
• Patients with confirmed or suspected decompensated hepatitis B cirrhosis including but not limited to: hepatic encephalopathy, hepatorenal syndrome, esophageal and gastric variceal bleeding, splenomegaly, ascites, primary liver cancer, etc. ;
• Patients with history of other malignancies or complicating with other malignant tumors;
• Patients complicating with severe circulatory, digestive, respiratory, urinary, blood, metabolism, immune, nervous and other systemic;
• Patients with acute infection within 2 weeks before screening;
• Patients who had participated in clinical trials of drugs or medical devices within 1 month before screening;
• Patients who could not ban smoking, drinking, caffeinated food or drinks within 2 days before administration and during the study , and patients who have special dietary requirements and can not follow the unified diet;
• Laboratory examination: platelet count\<90×10\^9/L; leukocyte count\<3.0×10\^9/L; neutrophil absolute value\<1.3×10\^9/L; serum total bilirubin\>2×ULN; albumin\<30 g/L; creatinine clearance rate≤60ml/min (calculated by MDRD formula); international standardization ratio value of prothrombin time (INR) \>1.5;

Sponsors & Collaborators

• Fujian Cosunter Pharmaceutical Co. Ltd: lead

Study Sites (1)

The first hospital of Jilin University

Changchun, Jilin, 130000, China

Location

Related Publications (1)

• Wu M, Mai J, Zhang H, Zhang G, Mao J, Tang Y, Yan W, Wu W, Hou J, Liang X, Liu Z, Ding Y, Niu J. Safety, pharmacokinetics, and antiviral efficacy of the novel capsid assembly modulator GST-HG141 in patients with chronic hepatitis B: a phase 1 trial with a randomized, placebo-controlled design. Virol J. 2024 Dec 20;21(1):328. doi: 10.1186/s12985-024-02584-8.

  PMID: 39707469 DERIVED

MeSH Terms

Conditions

Hepatitis B

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases

Study Officials

• Junqi Niu, PhD

  The First Hospital of Jilin University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2021
• First Posted: May 3, 2021
• Study Start: May 31, 2021
• Primary Completion: February 23, 2022
• Study Completion: March 14, 2022
• Last Updated: June 7, 2022

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)