Clinical trial NCT06829329: Study to Evaluate the Efficacy and Safety of AHB-137 in Treatment-naive Participants with CHB with Low Viral Load
Official title: A Randomized, Multi-center, Placebo-controlled Phase II Study to Evaluate the Efficacy and Safety of AHB-137 in Treatment-naive Participants with Chronic Hepatitis B with Low Viral Load
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: Hepatitis B, Chronic
Lead sponsor: Ausper Biopharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2025-02-17
Enrollment: 60
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: The study is to evaluate the efficacy and safety of AHB-137 in CHB participants. About 60 participants will be recruited and randomly divided into two arms.The arms will be stratified based on HBsAg level (HBsAg greater than\[\>\] 100 international unit per milliliter \[IU/mL\] to less than or equal to \[≤\]3000 IU/mL or greater than \[\>\] 3000 IU/mL to ≤10000 IU/mL) at screening. The total duration of the study, including screening phase (up to 28 days), treatment phase (16 weeks), and follow-up phase (24 weeks), with a total study duration of approximately 44 weeks for each participant.


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 according to the protocol;
2. Male or female participants aged 18-65 years old (including the boundary value) at the time of signing the ICF;
3. Male participants weighed higher than 50kg and female participants weighted higher than 50 kg, Body Mass Index (BMI) between 18 to 32 kg/m\^2(inclusive);
4. Participants with positive HBsAg or HBV DNA greater than or equal to (≥) 6 months prior to screening and has not received antiviral treatment with interferon or nucleos(t)ide analogue ;
5. At screening, 20 IU/mL\<HBV DNA≤2000 IU/mL;
6. At screening, 100 IU/mL\<HBsAg≤10000 IU/mL;
7. At screening, ALT\<3×upper limit of normal (ULN);
8. For women with childbearing potential should be non-pregnant or non-lactating during screening, and participants 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. Clinically significant abnormalities except chronic HBV infection;
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, Imaging-diagnosed moderate to severe fatty liver, drug-induced liver injury, history of hereditary liver disease, etc.;
3. Participants with severe infection requiring systemic anti-infection treatment 1 month before randomization;
4. Co-infection with current or past history of Hepatitis C virus (HCV), Human immunodeficiency virus (HIV), Hepatitis D virus (HDV).
5. Participants who have had or currently have cirrhosis or currently have progressive liver fibrosis;
6. Participants who have had or currently have hepatobiliary system tumor; Or blood alpha-fetoprotein (AFP) ≥ 20 ng/mL during screening, or the liver B-ultrasound, CT, MRI and other imaging examinations suggested the possibility of hepatobiliary system tumors;
7. The laboratory examination results are obviously abnormal;
8. History of vasculitis or signs and symptoms of potential vasculitis;
9. Anti-neutrophil cytoplasmic antibodies (ANCA) was positive at screening.
10. History of extrahepatic disease that may be related to HBV immune status;
11. 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;
12. History of malignancy within the past 5 years or the discovery of suspected tumors during the screening period;
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, whichever is longer;
17. Participants who have received any oligonucleotide or small molecule interfering ribonucleic acid (siRNA) drugs;
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 limit of detection (LOD) (0.05 IU/mL) and HBV DNA lower than lower limit of quantitation (LLOQ), with or without HBsAb
timeFrame: 16 weeks
measure: Safety: number of participants with treatment-emergent adverse events (TEAEs), treatment-related adverse events(TRAEs), serious adverse events (SAE) and clinically significant examination results
timeFrame: Up to 40 weeks
Secondary outcomes:
measure: Proportion of participants achieving sustained virologic response after stopping AHB-137 or placebo treatment
timeFrame: Up to 40 weeks
measure: Number of Participants With HBsAg<LOD (0.05 IU/mL) and the percentage of participants with different levels of HBsAg reduction compared with baseline
timeFrame: Up to 40 weeks
measure: Number of Participants With HBV DNA<LLOQ and the percentage of participants with different HBV DNA reduction
timeFrame: Up to 40 weeks
measure: Proportion of participants achieving HBsAg<LOD and HBV DNA<LLOQ, with or without HBsAb
timeFrame: Up to 40 weeks
measure: Serum levels of HBsAg, HBV DNA, HBV RNA, HBcrAg, HBsAb
timeFrame: Up to 40 weeks
measure: Changes of the score of hepatitis B quality of life instrument (HBQOL) compared with baseline
timeFrame: Up to 40 weeks
measure: Percentage of participants who reached HBeAg negative
timeFrame: Up to 40 weeks
measure: Percentage of participants achieving HBeAg seroconversion
timeFrame: Up to 40 weeks
measure: Proportion of participants with ALT normailzation in absence of rescue therapy.
timeFrame: Up to 40 weeks
measure: Time of ALT normalization in absence of rescue therapy
timeFrame: Up to 40 weeks
measure: Sequencing of the Viral DNA and/or viral RNA analysis for detection of drug resistance of AHB-137
timeFrame: Up to 40 weeks
measure: Immunogenicity: number and percentage of participants with detectable anti-drug antibodies (ADA)
timeFrame: Up to 40 weeks
measure: The pharmacokinetic profile of AHB-137: Maximum concentration (Cmax) of AHB-137 in plasma
timeFrame: Up to 40 weeks
measure: The pharmacokinetic profile of AHB-137: Area under the concentration-time curve (AUC) of AHB-137
timeFrame: Up to 40 weeks
measure: Plasma concentrations of AHB-137
timeFrame: Up to 40 weeks
Other outcomes:
Locations:
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
state: Chongqing
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: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
References: