Clinical trial NCT06452693: A Clinical Study to Evaluate the Efficacy of TQA3038 Injection in Patients With Chronic Hepatitis B
Official title: A Phase Ib/IIa Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetic, and Antiviral Efficacy of TQA3038 Injection in Patients With Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-06-11
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is divided into two parts. Phase Ib is a randomized, double-blind, placebo-controlled trial, designed to evaluate the safety, tolerability, pharmacokinetic characteristics, preliminary efficacy, and immunogenicity of TQA3038 injection in patients with chronic hepatitis B. It is expected to include 72 subjects. Phase IIa adopted an open-label, randomized, parallel-controlled design, with a total of 90 subjects included, mainly evaluating the changes in serum HBsAg compared to baseline at the end of the 48th week.


Eligibility criteria: Inclusion Criteria:

* Subjects voluntarily participate in this study and sign informed consent;
* Male and female ≥18 years old and ≤65 years old;
* Male subjects with a weight of ≥ 50 kilograms and female subjects with a weight of ≥ 45 kilograms, BMI 18\~28 kg/m2;
* Patients diagnosed with chronic hepatitis B (CHB) who have been serum HBsAg positive for more than 6 months and HBeAg positive ; During the screening period, 100 IU/ml ≤ HBsAg quantification ≤ 5000 IU/ml;
* The subjects are able to communicate well with the researchers, voluntarily and can understand and follow the experimental protocol process to complete the study;
* The subjects (including partners) are willing to voluntarily adopt effective contraceptive measures during the clinical trial period and long-term follow-up period, and specific contraceptive measures are shown in the appendix;
* The treated patients need to meet the condition:The subject must have received oral nucleoside (acid) drug treatment and a stable treatment regimen;
* Newly treated patients must meet the condition:During screening, the subjects had never received antiviral treatment for chronic hepatitis B B (oral nucleoside (acid) drugs and interferon), or had irregular antiviral treatment in the past, but had not received any antiviral treatment for chronic hepatitis B 3 months before enrollment.

Exclusion Criteria:

* Pregnant and lactating women;
* Chronic diseases other than chronic HBV infection with significant clinical significance that have a history of mental illness or are deemed unsuitable by researchers for participation in this study;
* Acute diseases with significant clinical significance occurring within 7 days prior to receiving the investigational drug;
* Individuals with a history of active pathological bleeding or a tendency towards bleeding;
* Prescription medication has been used within 14 days prior to receiving the study drug;
* Receive any preventive or attenuated vaccines within 14 days prior to receiving the study drug;
* Blood donors or those who have lost a significant amount of blood within the first 3 months of screening, or those who have donated blood during the planned study period;
* Subjects with a history of excessive alcohol consumption;
* A history of alcohol or drug abuse within the 12 months prior to screening, or a positive drug screening result during screening;
* Complicated with other infected disease;
* Patients with significant liver fibrosis or cirrhosis before or during screening;
* History of chronic liver diseases other than chronic HBV infection;
* Patients have a history of hepatocellular carcinoma (HCC) before or at the time of screening, or may be at risk for HCC;
* Used immunosuppressive or immunomodulatory drugs and cytotoxic drugs within 6 months prior to the study medication;
* During screening, subjects showed significant laboratory results abnormalities；
* Screening for tumors with a history of malignancy within the first 5 years, excluding tumors that can be completely cured through surgical resection;
* Uncontrollable chronic diseases;
* History of intolerance to subcutaneous injection;
* Participated in clinical studies of any drug or medical device within 3 months prior to drug administration or within 5 times the half-life of the investigational drug, or used the investigational drug;
* Those considered unsuitable for enrollment by the investigators.

Primary outcomes:
measure: Adverse events (AEs)
timeFrame: Baseline up to 16 weeks
measure: Serious adverse events (SAEs)
timeFrame: Baseline up to 16 weeks
measure: Hepatitis B virus surface antigen (HbsAg)
timeFrame: Baseline up to 48 weeks
Secondary outcomes:
measure: Time to Reach Maximum Plasma Concentration (Tmax)
timeFrame: Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose
measure: Maximum Plasma Concentration (Cmax)
timeFrame: Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose
measure: Area Under the Plasma Concentration Versus Time Curve (AUC)
timeFrame: Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose
measure: Volume of distribution (Vd/F)
timeFrame: Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose
measure: Apparent Plasma Clearance (CL/F)
timeFrame: Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose
measure: Apparent Terminal Elimination Half-life (t1/2)
timeFrame: Predose on the 1st dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose and Predose on the 2nd dose administration and 30 minutes, 1, 2, 4, 8, 24hours postdose
measure: The incidence and titer of anti drug antibodies (ADA)
timeFrame: Day1 before administration, Week 8, Week 16, and during withdrawal
measure: Incidence of Neutralization antibody (Nab)
timeFrame: Day1 before administration, Week 8, Week 16, and during withdrawal
measure: Hepatitis B surface antigen (HBsAg)
timeFrame: Baseline up to 48 weeks
measure: Hepatitis B E antigen (HBeAg)
timeFrame: Baseline up to 48 weeks
Other outcomes:
Locations:
city: Bengbu
country: China
facility: The First Affiliated Hospital of Bengbu Medical College
state: Anhui
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary Hospital of Fujian Medical University
state: Fujian
city: Lanzhou
country: China
facility: Gansu province people hospital
state: Gansu
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat sen University
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of GUANGXI Medical University
state: Guangxi
city: Guiyang
country: China
facility: Guizhou Provincial People's Hospital
state: Guizhou
city: Harbin
country: China
facility: The Fourth Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Shiyan
country: China
facility: Shiyan City Taihe Hospital
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital of Tongji medical college of HUST
state: Hubei
city: Changsha
country: China
facility: Xiangya Third Hospital of Central of Central Suoth University
state: Hunan
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The first hospital of Jilin University
state: Jilin
city: Changchun
country: China
facility: Hepatobiliary Hospital of Jilin
state: Jilin
city: Shenyang
country: China
facility: The sixth people's hospital at of Shenyang
state: Liaoning
city: Shenyang
country: China
facility: Shengjing Hospital Affiliated to China Medical University
state: Liaoning
city: Jinan
country: China
facility: Shandong Public Health Clinical Center
state: Shandong
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Urumqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Chongqing
country: China
facility: The Southwest Hospital of AMU
city: Chongqing
country: China
facility: The Second Affilated Hospital of Chongqing medical university
city: Shanghai
country: China
facility: Shanghai Tongren Hospital
city: Tianjin
country: China
facility: People's Hospital of Tianjin (City)
Study officials:
References: