Clinical trial NCT06993480: A Study to Evaluate the Antiviral Activity and Immune Response of AHB-137 Injection in Participants With Chronic Hepatitis B (CHB)
Official title: A Single-Center, Open-Label Phase II Clinical Study to Evaluate the Antiviral Activity and Immune Responses of AHB-137 Injection in Participants With HBeAg-Negative CHB Treated With Nucleos (t) Ide Analogues
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: Hepatitis B, Chronic
Lead sponsor: Ausper Biopharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-05-28
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: AB-10-8005 is a single-center, open-label Phase II clinical study to evaluate the antiviral activity and immune responses of AHB-137 injection in participants with HBeAg-negative CHB treated with nucleos (t) ide analogues.

Detailed description: The study is to evaluate the antiviral activity and immune response of AHB-137 injection in participants with HBeAg-negative CHB treated with nucleos(t)ide analogues. The study is proposed to enroll 20-30 patients, with a total study duration of approximately 56 weeks per participants, including a screening period (up to 4 weeks), a clinical study lead-in period (approximately 4 weeks), an AHB-137 treatment period (24 weeks) and a follow-up period (24 weeks).

Eligibility criteria: Inclusion Criteria:

* Voluntarily participated in the study and signed an informed consent form;
* Aged between 18 and 50 years at the time of signing the informed consent form;
* Body mass index (BMI) within the range of 18-30 kg/ m2;
* HBeAg negative at screening;
* HBsAg or HBV DNA positive for at least 6 months;
* Have been on continuous nucleos(t)ide analogues antiviral therapy for more than 6 months prior to screening;
* 100 IU/mL \< HBsAg ≤ 3000 IU/mL and HBV DNA \< 100 IU/mL at screening;
* Alanine aminotransferase (ALT) ≤ 2 × upper limit of normal (ULN);
* Effective contraception as required.

Exclusion Criteria:

* Clinically significant abnormalities other than a history of CHB infection;
* Concomitant clinically significant other liver diseases;
* Any serious infection other than CHB infection requiring intravenous anti-infective therapy within 1 month prior to screening;
* Active hepatitis C, Human immunodeficiency virus (HIV) positive, syphilis positive;
* Liver stiffness value (LSM) \> 9.0 kPa at screening;
* Diagnosis or suspicion of hepatocellular carcinoma, or alpha-fetoprotein (AFP) concentration ≥ 20 ng/mL at screening;
* Participants with confirmed or suspected hepatic decompensated hepatitis B cirrhosis;
* Liver biopsy at screening assessed severity of activity ≥ G3 grade and/or fibrosis reaching S4 stage;
* History of extrahepatic disease possibly related to HBV immune status;
* Ongoing or taking any immunosuppressive medication within 3 months prior to screening. Those who have used immunomodulators and cytotoxic drugs within 6 months prior to the first dose, or have a history of vaccination within 1 month prior to screening or have a live vaccination plan during the trial; Continuous use of traditional Chinese medicine for more than 2 months within 1 year prior to screening, or within 1 month prior to screening; Ongoing use of anticoagulants, bleeding tendency or coagulopathy, or conditions that, in the opinion of the investigator, increase the risk of liver biopsy;
* Receiving or using any interferon-containing therapy within 12 months prior to screening;
* History of malignancy within 5 years prior to screening or being evaluated for possible malignancy;
* Suspected history of allergy to any component of the study drug, or allergic constitution (multiple drug and food allergy, and judged by the investigator to be clinically significant);
* Major trauma or major surgery within 3 months prior to screening, or planned surgery during the study;
* Donation or blood loss ≥ 400 mL, or received blood transfusion within 12 weeks prior to screening; Or blood donation or blood loss ≥ 200 mL within 1 month prior to screening;
* Participants who are participating in another clinical trial, or have not undergone a protocol-specified washout period prior to this study;
* Received any antisense oligonucleotides (ASO) or small molecule interfering ribonucleic acid (siRNA) drug;
* Participants with abnormal thyroid function judged by the investigator to be ineligible for enrollment;
* Obviously abnormal laboratory test results;
* History of vasculitis or signs and symptoms of underlying vasculitis;
* Any other circumstance or condition that, in the opinion of the investigator, the participants are inappropriate for participation in the study.

Primary outcomes:
measure: Proportion of participants with serum HBsAg < limit of detection (LOD) 0.05 international unit per milliliter (IU/mL) and Hepatitis B Virus (HBV) DNA < lower limit of quantification (LLOQ) with or without HBsAb seroconversion.
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Number and percentage of participants with serum HBsAg < LOD and/or HBV DNA < LLOQ.
timeFrame: Up to 48 weeks
measure: Proportion of participants maintaining sustained response;
timeFrame: Up to 48 weeks
measure: The changes of liver HBsAg, HBcAg, HBV RNA, integration HBV DNA and covalently closed circular DNA (cccDNA) compared to baseline;
timeFrame: Up to 48 weeks
measure: The changes in the phenotype of liver immune cells compared to baseline;
timeFrame: Up to 48 weeks
measure: The changes of peripheral blood cytokines compared to baseline;
timeFrame: Up to 48 weeks
measure: The changes of peripheral blood immune cell phenotypes compared to baseline;
timeFrame: Up to 48 weeks
measure: The changes of serum HBsAg, HBsAb, HBV DNA, HBV RNA, HBeAg, HBeAb compared to baseline;
timeFrame: Up to 48 weeks
measure: The changes in peripheral blood metabolomics compared to baseline;
timeFrame: Up to 48 weeks
measure: The changes in peripheral blood proteomics compared to baseline;
timeFrame: Up to 48 weeks
measure: The changes in liver metabolomics compared to baseline, if applicable ;
timeFrame: Up to 48 weeks
measure: AHB-137 drug concentrations, and metabolite profiling, if applicable;
timeFrame: Up to 48 weeks
measure: Number and percentage of participants with detectable anti-drug antibodies (ADA);
timeFrame: Up to 48 weeks
measure: Safety: Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAE) and clinically significant examination results.
timeFrame: Up to 48 weeks
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
Study officials:
affiliation: The Second Affiliated Hospital of Chongqing Medical University
name: Dazhi Zhang
role: PRINCIPAL_INVESTIGATOR
References: