A Clinical Study of TQA3605 Tablets Monotherapy or in Combination With Nucleoside (Acid) Analogues in Treatment Naive and Treated Patients With Chronic Hepatitis B

Randomized, Double-blind, Placebo-controlled Phase Ib/IIa Clinical Trial to Evaluate the Efficacy and Safety of TQA3605 Tablets Monotherapy or in Combination With Nucleoside (Acid) Analogues in Treatment-naïve Patients and Treated Patients With Chronic Hepatitis B

A randomized, double-blind Phase Ib/IIa multicenter trial design was used. All eligible subjects received TQA3605 tablets/placebo plus nucleoside (acid) analogues. A total of 88 subjects were required

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Hepatitis b
• Intervention / Treatment: Drug: Entecavir dispersible tablets; Drug: Tenofovir disoproxil fumarate tablet; Drug: Tenofovir alafenamide fumarate tablet; Drug: TQA3605 tablets; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400010
      • The Second Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China, 400038
      • The First Affiliated Hospital of the Chinese People's Liberation Army Army Medical University
  • Shannxi
    • Xi'an, Shannxi, China, 710061
      • The First Affiliated Hospital of Xi'an Jiaotong University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects voluntarily participate in this study and sign informed consent;
• Male and female, ≥18 years old and ≤70 years old (subject to the date of signing the informed consent);
• Patients diagnosed with chronic hepatitis B (CHB) who have been serum HBsAg positive for more than 6 months and HBeAg positive or negative ;
• The liver fibrosis ultrasound transient imaging elastic technology (Fibroscan/FibroTouch) showed that the liver hardness (LSM) was less than 12.4 Kpa;
• Patients with chronic hepatitis B after treatment;
• Treatment-naïve patients of chronic hepatitis B patients;

Exclusion Criteria:

• Complicated with other infected disease such as hepatitis A virus (HAV), hepatitis C virus (HCV), Hepatitis D virus (HDV), hepatitis E virus (HEV), human immunodeficiency virus (HIV), syphilis (syphilis antibody positive and need treatment determined by the investigator);
• Abdominal ultrasound or other imaging or histology showed suspected cirrhosis or other liver disease before or during screening;
• Patients have a history of hepatocellular carcinoma (HCC) before or at the time of screening, or may be at risk for HCC;
• Active autoimmune disease diagnosed with immunodeficiency or undergoing systemic therapy which was continuing within 2 weeks before first dosing;
• Currently being treated with nephrotoxic drugs or drugs that alter renal excretion;
• Abnormal thyroid function;
• Renal diseases such as chronic kidney disease and renal insufficiency or creatinine clearance (CLCr) <60 ml/min during the screening period;
• Hematologic and biochemical abnormalities;
• History of allergy to the investigational drug or its excipients;
• Recipients of solid organs or bone marrow transplants;
• A history of malignant tumors within the past 5 years;
• Interstitial lung disease, acute lung disease, etc.;
• Uncontrolled systemic diseases such as high blood pressure and diabetes;
• Have used any investigational drug or participated in a clinical trial within one month prior to the administration of study drug;
• Those who received live attenuated vaccine within 28 days before the start of study treatment, inactivated vaccine within 7 days, or planned vaccination during the study period;
• The investigator determines that there is any medical or psychiatric condition that puts the subject at risk, interferes with participation in the study, or interferes with the interpretation of the study results;
• Female subjects that were pregnant, lactating or had a positive pregnancy result during the screening period or during the trial; Male and female patients with reproductive potential who were unwilling to use effective contraceptive methods during the study period;
• Subjects who have any medical condition that may affect the absorption of oral drugs;
• Within 12 weeks prior to screening, treated chronic hepatitis B patients who had stopped taking nucleoside (acid) analogues for more than 14 consecutive days;
• Those considered unsuitable for enrollment by the investigators.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo +Nucleoside (acid) analogs (NAs) combination therapy 24 weeks; Placebo and Nucleoside (acid) analogues, taken orally once daily, continue for 24 weeks.	Drug: Entecavir dispersible tablets; Entecavir inhibits viral replication and indicated for chronic hepatitis B treatment.; Drug: Tenofovir disoproxil fumarate tablet; Tenofovir disoproxil fumarate is a Nucleotide reverse transcriptase inhibitor.; Drug: Tenofovir alafenamide fumarate tablet; Tenofovir alafenamide fumarate inhibits hepatitis B virus replication.; Drug: Placebo; TQA3605 placebo tablets were orally administered on an empty stomach (at least 2 hours before or after meals) with warm.
Active Comparator: 50 mg of TQA3605 tablets +NAs combination therapy 24 weeks; 50 mg of TQA3605 tablets and Nucleoside (acid) analogues, taken orally once daily, continue for 24 weeks.	Drug: Entecavir dispersible tablets; Entecavir inhibits viral replication and indicated for chronic hepatitis B treatment.; Drug: Tenofovir disoproxil fumarate tablet; Tenofovir disoproxil fumarate is a Nucleotide reverse transcriptase inhibitor.; Drug: Tenofovir alafenamide fumarate tablet; Tenofovir alafenamide fumarate inhibits hepatitis B virus replication.; Drug: TQA3605 tablets; TQA3605 inhibits viral replication.
Active Comparator: 100 mg of TQA3605 tablets +NAs combination therapy 48 weeks; TQA3605 is taken orally 100mg once daily; Nucleoside (acid) analogues were used once daily for 48 weeks.	Drug: Entecavir dispersible tablets; Entecavir inhibits viral replication and indicated for chronic hepatitis B treatment.; Drug: Tenofovir disoproxil fumarate tablet; Tenofovir disoproxil fumarate is a Nucleotide reverse transcriptase inhibitor.; Drug: Tenofovir alafenamide fumarate tablet; Tenofovir alafenamide fumarate inhibits hepatitis B virus replication.; Drug: TQA3605 tablets; TQA3605 inhibits viral replication.
Active Comparator: 200 mg of TQA3605 tablets +NAs combination therapy 48 weeks; TQA3605 is taken orally 200mg once daily; Nucleoside (acid) analogues were used once daily for 48 weeks.	Drug: Entecavir dispersible tablets; Entecavir inhibits viral replication and indicated for chronic hepatitis B treatment.; Drug: Tenofovir disoproxil fumarate tablet; Tenofovir disoproxil fumarate is a Nucleotide reverse transcriptase inhibitor.; Drug: Tenofovir alafenamide fumarate tablet; Tenofovir alafenamide fumarate inhibits hepatitis B virus replication.; Drug: TQA3605 tablets; TQA3605 inhibits viral replication.
Placebo Comparator: Placebo +Nucleoside (acid) analogs (NAs) combination therapy; Placebo taken orally once daily, continue for 12 weeks. Placebo was then combined with nucleoside (acid) analogues (once daily) for 36 weeks	Drug: Entecavir dispersible tablets; Entecavir inhibits viral replication and indicated for chronic hepatitis B treatment.; Drug: Tenofovir disoproxil fumarate tablet; Tenofovir disoproxil fumarate is a Nucleotide reverse transcriptase inhibitor.; Drug: Tenofovir alafenamide fumarate tablet; Tenofovir alafenamide fumarate inhibits hepatitis B virus replication.; Drug: Placebo; TQA3605 placebo tablets were orally administered on an empty stomach (at least 2 hours before or after meals) with warm.
Active Comparator: 100 mg of TQA3605 tablets +NAs combination therapy; TQA3605 was taken orally 100mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.	Drug: Entecavir dispersible tablets; Entecavir inhibits viral replication and indicated for chronic hepatitis B treatment.; Drug: Tenofovir disoproxil fumarate tablet; Tenofovir disoproxil fumarate is a Nucleotide reverse transcriptase inhibitor.; Drug: Tenofovir alafenamide fumarate tablet; Tenofovir alafenamide fumarate inhibits hepatitis B virus replication.; Drug: TQA3605 tablets; TQA3605 inhibits viral replication.
Active Comparator: 200 mg of TQA3605 tablets +NAs combination therapy; TQA3605 was taken orally 200mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.	Drug: Entecavir dispersible tablets; Entecavir inhibits viral replication and indicated for chronic hepatitis B treatment.; Drug: Tenofovir disoproxil fumarate tablet; Tenofovir disoproxil fumarate is a Nucleotide reverse transcriptase inhibitor.; Drug: Tenofovir alafenamide fumarate tablet; Tenofovir alafenamide fumarate inhibits hepatitis B virus replication.; Drug: TQA3605 tablets; TQA3605 inhibits viral replication.
Active Comparator: 300 mg of TQA3605 tablets+NAs combination therapy; TQA3605 was taken orally 300mg once a day for 12 weeks. It was then combined with nucleoside (acid) analogues (once daily) for 36 weeks.	Drug: Entecavir dispersible tablets; Entecavir inhibits viral replication and indicated for chronic hepatitis B treatment.; Drug: Tenofovir disoproxil fumarate tablet; Tenofovir disoproxil fumarate is a Nucleotide reverse transcriptase inhibitor.; Drug: Tenofovir alafenamide fumarate tablet; Tenofovir alafenamide fumarate inhibits hepatitis B virus replication.; Drug: TQA3605 tablets; TQA3605 inhibits viral replication.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of adverse events (AEs)	The incidence of adverse events (AEs) during treatment	Up to 48 weeks
Severity of adverse events (AEs)	The severity of adverse events (AEs) during treatment	Up to 48 weeks
Incidence of serious adverse events (SAEs)	The incidence of serious adverse events (SAEs) during treatment	Up to 48 weeks
Severity of serious adverse events (SAEs)	The severity of serious adverse events (SAEs) during treatment	Up to 48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak time (Tmax)	Time to reach peak blood concentration after a single dose	pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.
Peak concentration	The highest plasma drug concentration that can be achieved after medication	pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.
Area under blood concentration-time curve (AUC)	The amount of drug absorbed into the human circulation after a single dose can be estimated using the area under the blood concentration-time curve	pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.
Apparent volume of distribution (Vd/F)	When a drug reaches homeostasis in the body, the ratio of the amount of drug in the body to the blood concentration is called the apparent volume of distribution.	pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.
Plasma clearance	The amount of plasma that the kidneys completely clear in unit time (per minute).	pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.
Elimination half-life	The time it takes for the plasma concentration to drop by half.	pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.
Steady state peak time	The time required to reach peak steady-state concentration after administration	pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.
Steady state maximum concentration	The highest blood concentration that occurs after stabilization	pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.
Steady state minimal concentration	The lowest blood concentration that occurs after stabilization	pre-dose, 30 minutes, 1 , 2 , 4 , 6 , 12, 24 hours after administration on Day 1; pre-dose on Day 8 and Day 9; pre-dose, 30 minutes, 1, 2, 4, 6, 12, 24 hours after administration on Day 10.
Incidence of abnormal laboratory test values	The incidence of abnormal laboratory values during treatment, e.g. triglycerides.	Up to 48 weeks
Severity of abnormal laboratory test values	The severity of abnormal laboratory values during treatment, e.g. triglycerides.	Up to 48 weeks
Deoxyribonucleic acid level of hepatitis B virus	Changes in hepatitis B virus deoxyribonucleic acid (HBV DNA) levels from baseline	At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study
Hepatitis B surface antigen	Changes in serum hepatitis B surface antigen (HBsAg) from baseline	At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study
Hepatitis B e antigen	Changes in serum hepatitis B e antigen (HBeAg) from baseline	At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study
Serologic clearance and/or serologic conversion of HBsAg	Proportion of subjects with HBsAg serologic clearance and/or serologic conversion	At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study
Serologic clearance and/or serologic conversion of HBeAg	Proportion of subjects with HBeAg serologic clearance and/or serologic conversion	At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study
Virological breakthrough rate	The proportion of subjects who achieved a virological breakthrough (defined as a confirmed increase of HBV DNA levels >1.0 log10 IU/ml from the minimum during treatment).	At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study

Collaborators and Investigators

• Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: November 20, 2023
• First Submitted That Met QC Criteria: November 27, 2023
• First Posted (Actual): November 29, 2023

Study Record Updates

• Last Update Posted (Estimated): November 14, 2024
• Last Update Submitted That Met QC Criteria: November 13, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis A; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir; Entecavir
• Other Study ID Numbers: TQA3605-Ib/IIa-01

Drug and device information, study documents

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