Clinical trial NCT06150014: A Clinical Study of TQA3605 Tablets Monotherapy or in Combination With Nucleoside (Acid) Analogues in Treatment Naive and Treated Patients With Chronic Hepatitis B
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Chronic Hepatitis b
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-11-29
Enrollment: 88
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: The incidence of adverse events (AEs)
timeFrame: Up to 48 weeks
measure: Severity of adverse events (AEs)
timeFrame: Up to 48 weeks
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 48 weeks
measure: Severity of serious adverse events (SAEs)
timeFrame: Up to 48 weeks
Secondary outcomes:
measure: Incidence of abnormal laboratory test values
timeFrame: Up to 48 weeks
measure: Severity of abnormal laboratory test values
timeFrame: Up to 48 weeks
measure: Deoxyribonucleic acid level of hepatitis B virus
timeFrame: At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study
measure: Hepatitis B surface antigen
timeFrame: At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study
measure: Hepatitis B e antigen
timeFrame: At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study
measure: Serologic clearance and/or serologic conversion of HBsAg
timeFrame: At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study
measure: Serologic clearance and/or serologic conversion of HBeAg
timeFrame: At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study
measure: Virological breakthrough rate
timeFrame: At week 12, week 24, week 36 and week 48 or when subjects withdrawal from the study
measure: Peak time (Tmax)
timeFrame: 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.
measure: Peak concentration
timeFrame: 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.
measure: Area under blood concentration-time curve (AUC)
timeFrame: 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.
measure: Apparent volume of distribution (Vd/F)
timeFrame: 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.
measure: Plasma clearance
timeFrame: 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.
measure: Elimination half-life
timeFrame: 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.
measure: Steady state peak time
timeFrame: 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.
measure: Steady state maximum concentration
timeFrame: 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.
measure: Steady state minimal concentration
timeFrame: 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.
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Chongqing
country: China
facility: The First Affiliated Hospital of the Chinese People's Liberation Army Army Medical University
state: Chongqing
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shannxi
Study officials:
References: