Chronic Hepatitis B
Conditions
Keywords
Chronic Hepatitis B
Brief summary
This study is a randomized, double-blind, placebo-controlled, multicenter phase 2 study to assess the efficacy and safety of AHB-137 injection in treatment-naïve participants with chronic hepatitis B.
Interventions
DRUGAHB-137
AHB-137 will be administered subcutaneously.
DRUGPlacebo
Placebo will be administered subcutaneously.
Sponsors
Ausper Biopharma Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Volunteer to participate and sign the informed consent form, and are willing to complete the study in accordance with the requirements of the protocol. * Aged 18-65 years (including boundary values). * Body mass index between the range of 18-32 kg/m2 (inclusive boundary values). * HBsAg or HBV DNA positive for ≥ 6 months at screening and no antiviral treatment with interferon or nucleoside analogue. * HBsAg and HBV DNA values met protocol requirements at screening. * ALT \< 3xULN at screening. * Use highly effective contraception as required.
Exclusion criteria
* Uncontrolled and stable clinically significant abnormalities other than a history of chronic HBV infection. * Participants with other clinically significant liver diseases, previous/current manifestations of hepatic decompensation, and a history of extrahepatic diseases that may be related to HBV immune status. * Any serious infection other than chronic hepatitis B infection requiring intravenous anti-infective therapy within 1 month prior to randomization. * Hepatitis C virus (HCV) infection or \< 12 months from cure at screening (HCV RNA positive within 12 months), human immunodeficiency virus (HIV) positive at screening, and syphilis positive (treponema pallidum antibody positive). * Significant fibrosis or cirrhosis, or liver stiffness value (LSM) \> 9.0 kPa at screening. * Participants with confirmed or suspected liver cancer who have a history of malignancy within the past 5 years or are undergoing assessment for a possible malignancy. * Laboratory test results do not meet the criteria. * Prior/current autoimmune disease, history of vasculitis, or presence of signs, symptoms, or laboratory tests of underlying vasculitis. * Fridericia ' s formula corrected QT interval (QTcF) ≥ 450 msec for male participants and ≥ 470 msec for female participants at screening. * Allergic to AHB-137 ingredients, or history of drug allergy or other allergies. * Major trauma or major surgery within 3 months prior to screening, or planned surgery during the trial. * Participants are participating in another clinical trial or failing to wash out as required. * Current use or use of any immunosuppressive medication (e.g. prednisone) within 3 months prior to screening, except for short courses (≤ 2 weeks) or use of topical/inhaled steroids;Those who have used immunomodulators within 3 months prior to screening;Those who have used cytotoxic drugs within 6 months prior to screening;History of vaccination within 1 month prior to screening or a live vaccination plan during the trial. * Participants that require regular long-term anticoagulants. * Abnormal thyroid function. * Participants that have received any antisense oligonucleic acid, siRNA, capsid assembly modulator (CAM) antiviral drug used to treat chronic hepatitis B. * Any other circumstances or conditions in which, in the opinion of the investigator, the participant is inappropriate for participation in this trial.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| HBV DNA < lower limit of quantitation (LLOQ), 10 IU/mL, HBsAg < limit of detection (LOD), 0.05 IU/mL with or without hepatitis B virus surface antibody (HBsAb) 24 weeks after discontinuation of all chronic hepatitis B treatment. | Up to 48 weeks. |
| Highly sensitive HBsAg < 0.005 IU/mL and HBV DNA < LLOQ (10 IU/mL) at the end of treatment. | Up to 48 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HBV DNA < LLOQ, 10 IU/mL, and HBsAg < 10 IU/mL 24 weeks after discontinuation of all chronic hepatitis B treatment. | Up to 48 weeks. | — |
| HBV DNA < LLOQ 24 weeks after discontinuation of all chronic hepatitis B treatment. | Up to 48 weeks. | — |
| HBV DNA < LLOQ and HBsAg < 100 IU/mL 24 weeks after discontinuation of all chronic hepatitis B treatment. | Up to 48 weeks. | — |
| HBsAg seroconversion rate 24 weeks after discontinuation of all chronic hepatitis B treatment. | Up to 48 weeks. | HBsAg seroconversion : serum HBsAg\<LOD, and at the same time or subsequently, HBsAb\>10 IU/L. |
| HBeAg seroconversion rate 24 weeks after discontinuation of all chronic hepatitis B treatment. | Up to 48 weeks. | HBeAg seroconversion:HBeAg negative, with simultaneous or subsequent positivity for HBeAb. |
| Proportion of participants who discontinued all chronic hepatitis B treatment at the end of treatment. | Up to 48 weeks. | — |
| HBV DNA < LLOQ and HBsAg < LOD rate and HBV DNA < LLOQ and HBsAg < 10 IU/mL rate by visit. | Up to 48 weeks. | — |
| HBsAg, HBeAg seroconversion rates by visit. | Up to 48 weeks. | HBsAg seroconversion: serum HBsAg\<LOD, and at the same time or subsequently, HBsAb\>10 IU/L. HBeAg seroconversion: HBeAg negative, with simultaneous or subsequent positivity for HBeAb. |
| Test Values of Virological Parameters. | Up to 48 weeks. | HBsAb, HBsAg, HBV DNA values and changes from baseline at each visit. |
| Time to first achievement of HBsAg and first HBeAg seroconversion. | Up to 48 weeks. | HBsAg seroconversion: serum HBsAg\<LOD, and at the same time or subsequently, HBsAb\>10 IU/L. HBeAg seroconversion: HBeAg negative, with simultaneous or subsequent positivity for HBeAb. |
| Changes of the hepatitis B quality of life (HBQOL) instrument in participants compared with baseline. | Up to 48 weeks. | Response options range from 1 to 5 with higher scores indicating more severe impact . |
| Changes of the score of EuroQol Five-Dimension Five-Level Scale (EQ-5D-5L) in participants compared with baseline. | Up to 48 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 participant's health state. |
| Proportion of participants with protocol-defined virologic response for HBsAg and HBV DNA. | Up to 48 weeks. | — |
| Change from baseline in alanine aminotransferase (ALT) and noninvasive assessment of liver fibrosis at each visit. | Up to 48 weeks. | — |
| Time to normalization of ALT without rescue therapy (for participants with abnormal baseline ALT). | Up to 48 weeks. | — |
| AHB-137 resistance analysis. | Up to 48 weeks. | Method: Sequencing of HBV DNA/RNA. |
| Proportion of participants who are HBeAb positive and HBeAg negative, and the test values of HBsAb, HBsAg and HBV DNA meet certain conditions. | Up to 48 weeks. | — |
| Safety: number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAE) and clinically significant examination results. | Up to 48 weeks. | Examination including laboratory examination, electrocardiogram (ECG) examination. |
| Proportion of participants with positive anti-drug antibody (ADA) and ADA level at each visit. | Up to 48 weeks. | — |
| Plasma drug concentration of AHB-137. | Up to 48 weeks. | — |
Countries
China
Contacts
CONTACTLu
PRINCIPAL_INVESTIGATORYunqing Qiu
Zhejiang University
PRINCIPAL_INVESTIGATORPeng Hu
The Second Affiliated Hospital of Chongqing Medical University
Outcome results
None listed