Clinical trial NCT06550128: Study to Evaluate the Efficacy and Safety of AHB-137 Injection in Subjects With Chronic Hepatitis B (CHB).
Official title: Randomized, Multi-center Phase II Study to Evaluate the Efficacy and Safety of AHB-137 in HBeAg-negative CHB Subjects Under Stable Nucleos(t)Ide Analogue (NA) Treatment
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Hepatitis B, Chronic
Lead sponsor: Ausper Biopharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-08-12
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: AB-10-8003 is a randomized, multi-center phase II study to evaluate the efficacy and safety of AHB-137 in subjects with HBeAg-negative CHB under stable NA treatment.

Detailed description: The study is to evaluate the efficacy and safety of AHB-137 in HBeAg-negative CHB subjects. About 60 subjects will be recruited and randomly divided into two cohorts. The total duration of the study, including screening phase (up to 28 days), AHB-137 ON treatment phase (up to 24 weeks); AHB-137 OFF treatment phase (24 weeks); and follow-up phase (24 weeks). Cohort A will be treated with AHB-137 for 24 weeks during the AHB-137 ON treatment phase, while Cohort B will be administered with placebo for the first 8 weeks followed by AHB-137 dosing for 16 weeks during the AHB-137 ON treatment phase.

Eligibility criteria: Inclusion Criteria:

1. Participants voluntarily participate in the study, and sign the Informed Consent Form (ICF) prior to screening, able to complete the study and discontinue their NA therapy according to the protocol;
2. At least 18 years old at the time of signing of the informed consent;
3. Body Mass Index (BMI) between 18 to 32 kg/m\^2(inclusive) ;
4. Participants who are Hepatitis B envelop antigen (HBeAg) negative during screening;
5. Participants whose serum HBsAg positive for at least 6 months prior to screening;
6. Participants who have stable on NA therapy at least 6 months prior to screening;
7. Participants with HBsAg concentration \>100 IU/mL and≤3000 IU/mL, HBV DNA\<100 IU/mL;
8. Participants with alanine aminotransferase (ALT)≤ 2x upper limit of normal (ULN);
9. For women of childbearing potential, she should be non-pregnant or non-lactating during screening, and participants (and partners) are willing to take effective contraceptive measures from the screening until the last visit or at least 6 months after the last dosing.

Exclusion Criteria:

1. Clinical significant abnormalities except Chronic HBV infection, such as acute coronary syndrome within 6 months before screening, evidence of major surgery, major or unstable heart disease, bleeding tendency or significant coagulation disorder within 3 months before screening;
2. Any clinically significant liver diseases, including but not limited to hepatitis caused by other pathogenic infections, hemochromatosis, Wilson disease, primary biliary cirrhosis, autoimmune liver diseases, alcoholic liver disease, severe non-alcoholic fatty liver disease, Drug-induced liver injury, etc.;
3. Participants with severe infection requiring intravenous anti-infection treatment 1 month before randomization;
4. Co-infection with: hepatitis C virus, human immunodeficiency virus (HIV) and hepatitis D virus;
5. Liver stiffness measurement (LSM)≥9.0 kPa when screening;
6. Diagnosed or suspected hepatocellular carcinoma;
7. The laboratory examination results are obviously abnormal;
8. History of vasculitis or signs and symptoms of potential vasculitis;
9. History of extrahepatic disease that may be related to HBV immune status;
10. Administration of immunosuppressants within 3 months prior to screening, except for short-term use (≤2 weeks) or topical/inhaled steroids. Administration of immunomodulators (thymosin) and cytotoxic drugs within 6 months prior to the first study intervention or have a history of vaccination within 1 month prior to screening or planned administration during the study.
11. Administration of any Interferon within 6 months prior to screening;
12. History of malignant tumor within the past 5 years;
13. Any suspicion of drug component allergy, or allergic constitution (various drug and food allergy, and judged by the investigator to be clinically significant) in participants;
14. Participants who have significant trauma or major surgery within 3 months before screening, or plan to perform surgery during the study;
15. Blood donation or blood loss more than 400 mL within 12 weeks before screening; Blood transfusion; Blood donation or blood loss not less than 200 mL within 1 month before screening;
16. Concurrently participating in another clinical study, or received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives or twice the duration of the biological effect of the study treatment or 90 days;
17. Any oligonucleotide or siRNA treatments within 12 months prior to first dosing;
18. Any other circumstances or conditions for which the investigator considers that the participants are inappropriate to participate in the study.

Primary outcomes:
measure: Proportion of participants achieving HBsAg lower than lower limit of quantification(LLOQ )(0.05 IU/mL) and HBV DNA lower than LLOQ , regardless of whether HBsAg seroconversion is observed
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Proportion of participants achieving HBsAg lower than LLOQ and HBV DNA lower than LLOQ , regardless of whether HBsAg seroconversion is observed
timeFrame: At 8 weeks
measure: Proportion of participants achieving sustained virologic response (SVR) measured by HBsAg and HBV DNA levels
timeFrame: Up to 48 weeks
measure: Proportion of participants maintain HBsAg lower than LLOQ (0.05 IU/mL) and HBV DNA lower than LLOQ, regardless of whether HBsAg seroconversion is observed
timeFrame: Up to 48 weeks
measure: Changes of the score of hepatitis B quality of life instrument (HBQOL) compared with baseline
timeFrame: Up to 72 weeks
measure: Percentage of participants with different levels of HBsAg reduction compared with baseline
timeFrame: Up to 72 weeks
measure: Serum levels of HBV DNA, HBsAg, highly sensitive HBsAg (<0.005 IU/mL), HBcrAg, HBV RNA, HBsAb, HBeAb and HBsAg-HBsAb.
timeFrame: Up to 72 weeks
measure: The number and percentage of participants whose HBsAg and/or HBV DNA decreased to below the LLOQ
timeFrame: Up to 72 weeks
measure: The time from the end of AHB-137 OFF treatment to virological relapse
timeFrame: Up to 72 weeks
measure: The time from the end of AHB-137 OFF treatment to clinical relapse
timeFrame: Up to 72 weeks
measure: Sequencing of the Viral DNA and/or viral RNA analysis for detection of drug resistance of AHB-137
timeFrame: Up to 24 weeks
measure: Safety: number of participants with adverse events (TEAEs), serious adverse events (SAE) and clinically significant examination results, including laboratory examination, electrocardiogram (ECG) examination, physical examination and vital signs
timeFrame: Up to 72 weeks
measure: Immunogenicity: number and percentage of participants with detectable anti-drug antibodies (ADA)
timeFrame: Up to 72 weeks
measure: Changes of cytokine levels compared with baseline
timeFrame: Up to 72 weeks
measure: The pharmacokinetic profile of AHB-137: Maximum concentration (Cmax) of AHB-137 in plasma
timeFrame: Up to 72 weeks
measure: The pharmacokinetic profile of AHB-137: Area under the concentration-time curve (AUC) of AHB-137
timeFrame: Up to 72 weeks
measure: Plasma concentrations of AHB-137
timeFrame: Up to 72 weeks
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary Hospital of Fujian Medical University
state: Fujian
city: Zhenjiang
country: China
facility: The third People's Hospital of Zhenjiang
state: Jiangsu
city: Beijing
country: China
facility: Beijing Friendship Hospital, Capital Medical University
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
city: Jilin
country: China
facility: The First Hospital of Jilin University
Study officials:
affiliation: The First Hospital of Jilin University
name: Junqi Niu
role: PRINCIPAL_INVESTIGATOR
affiliation: Nanfang Hospital, Southern Medical University
name: Jinlin Hou
role: PRINCIPAL_INVESTIGATOR
References: