Study to Evaluate the Efficacy and Safety of AHB-137 Injection in Subjects With Chronic Hepatitis B (CHB).

Phase 2

Active, not recruiting

• Conditions: Hepatitis B, Chronic
• Interventions: Drug: AHB-137 injection; Drug: Placebo

• Registration Number: NCT06550128
• Lead Sponsor: Ausper Biopharma Co., Ltd.

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.

Study Timeline

• Study Start: 2024-07-05
• Status Verified: 2024-08
• Study First Submitted: 2024-08-05
• Study First Submitted QC: 2024-08-08
• Study First Posted: 2024-08-12
• Last Update Submitted: 2025-04-22
• Last Update Posted: 2025-04-23
• Primary Completion: 2025-06-02
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AHB-137	AHB-137 injection	AHB-137 300 mg will be injected subcutaneously once a week with a loading dose during each of the first two weeks.
AHB-137	Placebo	AHB-137 300 mg will be injected subcutaneously once a week with a loading dose during each of the first two weeks.
Placebo	Placebo	Placebo will be injected subcutaneously once a week for the first 8 weeks, with a loading dose during each of the first two weeks. Afterwards, AHB-137 will be injected subcutaneously once a week, until the 24th week.
Placebo	AHB-137 injection	Placebo will be injected subcutaneously once a week for the first 8 weeks, with a loading dose during each of the first two weeks. Afterwards, AHB-137 will be injected subcutaneously once a week, until the 24th week.

Primary Outcome Measures

Name	Time	Method
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	Up to 24 weeks

Secondary Outcome Measures

Name	Time	Method
Immunogenicity: number and percentage of participants with detectable anti-drug antibodies (ADA)	Up to 72 weeks
Plasma concentrations of AHB-137	Up to 72 weeks
Percentage of participants with different levels of HBsAg reduction compared with baseline	Up to 72 weeks
The time from the end of AHB-137 OFF treatment to virological relapse	Up to 72 weeks
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	Up to 72 weeks
The pharmacokinetic profile of AHB-137: Maximum concentration (Cmax) of AHB-137 in plasma	Up to 72 weeks
Proportion of participants achieving sustained virologic response (SVR) measured by HBsAg and HBV DNA levels	Up to 48 weeks
Changes of the score of hepatitis B quality of life instrument (HBQOL) compared with baseline	Up to 72 weeks	The HBQOL consists of 31 items and 6 domains: psychological well-being, anticipation anxiety, vitality, stigma, transmissibility and vulnerability. Response options range from 1 to 5 with higher scores indicating more severe impact of Hepatitis B than lower scores.
The time from the end of AHB-137 OFF treatment to clinical relapse	Up to 72 weeks
Proportion of participants achieving HBsAg lower than LLOQ and HBV DNA lower than LLOQ , regardless of whether HBsAg seroconversion is observed	At 8 weeks
Serum levels of HBV DNA, HBsAg, highly sensitive HBsAg (<0.005 IU/mL), HBcrAg, HBV RNA, HBsAb, HBeAb and HBsAg-HBsAb.	Up to 72 weeks
The number and percentage of participants whose HBsAg and/or HBV DNA decreased to below the LLOQ	Up to 72 weeks
Sequencing of the Viral DNA and/or viral RNA analysis for detection of drug resistance of AHB-137	Up to 24 weeks
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	Up to 48 weeks
Changes of cytokine levels compared with baseline	Up to 72 weeks
The pharmacokinetic profile of AHB-137: Area under the concentration-time curve (AUC) of AHB-137	Up to 72 weeks

Trial Locations

Locations (6)

Mengchao Hepatobiliary Hospital of Fujian Medical University; 🇨🇳 Fuzhou, Fujian, China

The third People's Hospital of Zhenjiang; 🇨🇳 Zhenjiang, Jiangsu, China

Beijing Friendship Hospital, Capital Medical University; 🇨🇳 Beijing, China

The Second Affiliated Hospital of Chongqing Medical University; 🇨🇳 Chongqing, China

Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, China

The First Hospital of Jilin University; 🇨🇳 Jilin, China