A Multicenter Study of AHB-137 Injection Combined With Other Hepatitis B Drugs

Official title

A Randomized, Open-Label, Multicenter Phase II Study to Evaluate the Efficacy and Safety of AHB-137 Injection in Combination With Hepatitis B Vaccine or Pegylated Interferon α-2b (Peg-IFN) in Participants With HBeAg-Negative Chronic Hepatitis B (CHB) Treated With Nucleos(t)Ide Analogue (NAs)

Overview

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

• Drug AHB-137
  AHB-137 will be injected.
• Drug Peg-IFN
  Peg-IFN will be administered .
• Drug Hepatitis B Vaccine
  Hepatitis B vaccine will be administered.

Primary outcome measures

• 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. [Time frame: up to 72 weeks]

Secondary outcome measures (12)

• Proportion of participants with persistent HBsAg < LOD and HBV DNA < LLOQ . [Time frame: Up to 72 weeks]
• Detection of the serum concentration of HBsAg, HBsAb, HBV DNA, HBV RNA, HBcrAg, HBeAb,and HBeAg. [Time frame: Up to 72 weeks]
• Proportion of participants who met discontinuation criteria for NAs treatment at the end of the treatment period. [Time frame: Up to 48 weeks]
• Relapse rate after discontinuation of NAs therapy. [Time frame: Up to 72 weeks]
• Change from baseline in alanine aminotransferase (ALT) values and time to normalization of values. [Time frame: Up to 72 weeks]
• Relapse time after discontinuation of NAs therapy. [Time frame: Up to 72 weeks]
• Plasma concentrations of AHB-137. [Time frame: Up to 48 weeks]
• Serum concentrations of Peg-IFN. [Time frame: Up to 48 weeks.]
• Safety: Number and percentage of participants with detectable anti-drug antibodies (ADA). [Time frame: Up to 72 weeks]
• Safety: Changes of the hepatitis B quality of life (HBQOL) instrument in participants compared with baseline. [Time frame: Up to 72 weeks]
• Safety: Number of participants with treatment-emergent adverse events (TEAEs), serious adverse events (SAE) and clinically significant examination results. [Time frame: Up to 72 weeks]
• Safety: Monitoring the score changes of Columbia Suicide Severity Scale (CSSRS) . [Time frame: Up to 72 weeks.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 14 centers

• Beijing Friendship Hospital, Capital Medical University — Beijing
• AusperBio Investigational Site — Chongqing
• AusperBio Investigational Site — Fuzhou
• AusperBio Investigational Site — Guangzhou
• AusperBio Investigational Site — Guangzhou
• AusperBio Investigational Site — Shenzhen
• AusperBio Investigational Site — Shenzhen
• AusperBio Investigational Site — Zunyi
• … and 6 more centers

Identifiers

NCT: NCT07069569 · AB-10-8007

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗