Chronic Hepatitis B
Conditions
Keywords
Hepatitis B, Chronic
Brief summary
This is a randomized, open-label, multicenter phase II study to evaluate the efficacy and safety of AHB-137 injection in combination with other hepatitis B drugs in participants with HBeAg-negative CHB treated with NAs.
Interventions
Sponsors
Ausper Biopharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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; * Aged between 18 and 65 years at the time of signing the ICF; * 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; * Continue antiviral therapy with a single nucleoside (t) ide analogue for more than 6 months prior to screening; * Alanine aminotransferase (ALT) ≤ 2 × upper limit of normal (ULN); * Effective contraception as required.
Exclusion criteria
* Participants who are not eligible for treatment with Peg-IFN/recombinant hepatitis B vaccine; * Clinically significant abnormalities other than a history of chronic HBV infection; * Concomitant clinically significant other liver diseases; * Any serious infection other than chronic hepatitis B infection requiring intravenous anti-infective therapy within 1 month prior to screening; * HCV RNA positive, Human immunodeficiency virus (HIV) positive, syphilis positive; * Significant liver fibrosis or cirrhosis at screening, or a liver stiffness value (LSM) \> 9.0 kPa; * Previous/current manifestations of hepatic decompensation; * Diagnosis or suspicion of hepatocellular carcinoma, or alpha-fetoprotein concentration (AFP) ≥ 20 ng/mL at screening; * Obviously abnormal laboratory test results; * History of vasculitis or presence of signs, symptoms, or laboratory tests of underlying vasculitis, and previous/current other diseases that may be related to vasculitic conditions; * QT interval corrected for heart rate (Fridericia method) abnormal; * History of extrahepatic disease possibly related to HBV immune status; * Participants with a history of malignancy within the past 5 years or who are being evaluated for a possible malignancy; * Serious mental illness or history of serious mental illness prior to screening; * Suspected history of allergy to any component of the study drug, or allergic constitution; * Major trauma or major surgery within 3 months prior to screening, or planned surgery during the study; * Those who are participating in another clinical trial, or have not undergone a protocol-specified washout period prior to this study; * Current use or use of any immunosuppressive medication within 3 months prior to screening, with the exception of short courses (≤ 2 weeks) or use of topical/inhaled steroids;Those who have used immunomodulators and cytotoxic drugs within 6 months prior to the first dose;Or a history of vaccination within 6 months prior to screening or a live vaccination plan during the trial; * Participants requiring regular long-term administration of anticoagulants or antiplatelet drugs; * Thyroid dysfunction; * Patients with uncontrolled epilepsy and other progressive neurological disorders; * Received any antisense oligonucleotides (ASO) or small molecule interfering ribonucleic acid (siRNA) drug; * Any other circumstance or condition that, in the opinion of the investigator, the participants are inappropriate for participation in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of participants with persistent HBsAg < limit of detection (LOD) and HBV DNA < lower limit of quantification (LLOQ) at the 24th week after all treatment for CHB was discontinued. | up to 72 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Detection of the serum concentration of HBsAg, HBsAb, HBV DNA, HBV RNA, HBcrAg, HBeAb,and HBeAg. | Up to 72 weeks | — |
| Proportion of participants who met discontinuation criteria for NAs treatment at the end of the treatment period. | Up to 48 weeks | — |
| Relapse rate after discontinuation of NAs therapy. | Up to 72 weeks | — |
| Change from baseline in alanine aminotransferase (ALT) values and time to normalization of values. | Up to 72 weeks | — |
| Relapse time after discontinuation of NAs therapy. | Up to 72 weeks | — |
| Plasma concentrations of AHB-137. | Up to 48 weeks | — |
| Proportion of participants with persistent HBsAg < LOD and HBV DNA < LLOQ . | Up to 72 weeks | — |
| Safety: Number and percentage of participants with detectable anti-drug antibodies (ADA). | Up to 72 weeks | — |
| Safety: Changes of the hepatitis B quality of life (HBQOL) instrument in participants compared with baseline. | Up to 72 weeks | This scale has 31 items, including 7 dimensions: psychological status, expected anxiety, vitality, shame, infectivity, health vulnerability, and viral response. Each item is scored on a 5-point scale, with higher scores indicating a more severe impact of hepatitis B on quality of life. |
| Safety: Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAE) and clinically significant examination results. | Up to 72 weeks | Examination including laboratory examination, electrocardiogram (ECG) examination. |
| Safety: Monitoring the score changes of Columbia Suicide Severity Scale (CSSRS) . | Up to 72 weeks. | The CSSRS is a categorical, interviewer-rated instrument that screens for suicidal ideation (five items, 0-1 each) and suicidal behavior (six items, 0-1 each); the highest positive item defines the risk level rather than a total score. For ideation items 3-5 an additional 0-5 intensity rating can be recorded. Across all items the minimum value is 0 (absent) and the maximum is 1 (present); a score of 1 on any item indicates a worse outcome and triggers escalating clinical safeguards, with any behavior item being tantamount to a suicidal event. |
| Safety: Changes of the score of EuroQol Five-Dimension Five-Level Scale (EQ-5D-5L) in participants compared with baseline. | Up to 72 weeks | The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. |
| Safety: Monitoring the score changes of Self-Rating Depression Scale (SDS). | Up to 72 weeks. | The SDS is a 20-item, 4-point Likert self-report scale that yields a raw sum of 20-80 points, conventionally converted to a standard score of 25-100 by multiplying the raw total by 1.25. Higher standard scores denote worse outcomes: \<50 normal, 50-59 mild, 60-69 moderate, and ≥70 severe depression, with ≥70 warranting specialist evaluation and suicide-risk assessment. |
| Serum concentrations of Peg-IFN. | Up to 48 weeks. | — |
Countries
China
Outcome results
None listed