This study is a randomized, open-label, multicenter phase 2 clinical trial to evaluate the efficacy and safety of AHB-137 injection in participants with HBeAg-negative CHB treated with NAs.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
84
Subcutaneous injection
St Vincents Hospital Melbourne
Fitzroy, Victoria, Australia
Queen Mary Hospital - PPDS
Hong Kong, China
New Zealand Clinical Research
Grafton, Auckland, New Zealand
National University Hospital - Singapore
Singapore, Singapore
Proportion of participants with sustained response post AHB-137 treatment
Sustained response defined as hepatitis B surface antigen (HBsAg) level below the limit of detection (LOD, 0.05 international units \[IU\]/mL) and HBV deoxyribonucleic acid (DNA) below the lower limit of quantification (LLOQ)
Time frame: 24 Weeks post AHB-137 treatment
Proportion of participants with functional cure (FC) or sustained HBV DNA response off all HBV treatment
Time frame: Off-treatment follow-up (Week 48 to 96)
Proportion of participants with functional cure (FC)
Time frame: Week 72
Proportion of participants with sustained HBV DNA response
Time frame: From baseline through Week 72
Proportion of participants with HBsAg ≤10 IU/mL and HBV DNA < Lower Limit of Quantification (LLOQ) post AHB-137 treatment
Time frame: 24 weeks post AHB-137 treatment
Proportion of participants with HBsAg <100 IU/mL and HBV DNA < LLOQ
Time frame: 24 weeks post AHB-137 treatment and at Week 72
Proportion of participants with complete response (CR)
Time frame: From baseline through end of study (Week 96)
Proportion of participants with HBsAg < or ≥ LOD (0.05 IU/mL) and/or HBV DNA < or ≥ LLOQ
Time frame: From baseline through end of study (Week 96)
Proportion of participants with ultrasensitive HBsAg < LOD (0.005 IU/mL)
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Asan Medical Center
Seoul, South Korea
Chiayi Christian Hospital
Chiayi City, Taiwan
E-DA Hospital
Kaohsiung City, Taiwan
National Taiwan University Hospital
Taipei, Taiwan
Time frame: From baseline through end of study (Week 96)
Proportion of participants with HBsAg ≤ 10 IU/mL and < 100 IU/mL
Time frame: From baseline through end of study (Week 96)
Proportion of participants that meet nucleos(t)ide analog (NA) discontinuation criteria
Time frame: Week 48
Categorical change from baseline in serum hepatitis B surface antigen (HBsAg) levels, defined as reductions of ≥0.5, ≥1.0, ≥1.5, ≥2.0, or ≥3.0 log₁₀ IU/mL, assessed at each scheduled study visit
Time frame: From baseline through end of study (Week 96), assessed at each scheduled visit
Proportion of participants with anti-HBs seroconversion (with hepatitis B surface antibody [HBsAb] > 10 IU/L)
Time frame: Weeks 24, 48, and 72
Quantitative hepatitis B virologic and serologic markers over time
Actual values and change from baseline over time in quantitative hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), hepatitis B virus (HBV) DNA, HBV ribonucleic acid (RNA), hepatitis B core-related antigen (HBcrAg), hepatitis B e antibody (HBeAb), and hepatitis B e antigen (HBeAg), summarized descriptively.
Time frame: From baseline through end of study (Week 96)
Proportion of participants who experience virologic relapse
Time frame: From baseline through Week 72
Time from nucleos(t)ide analog (NA) therapy discontinuation to virologic relapse
Time frame: From NA therapy discontinuation (Week 48) through end of follow-up (Week 96)
Change from baseline in alanine aminotransferase (ALT)
Time frame: From baseline through end of study (Week 96)
Proportion of participants with baseline ALT above the upper limit of normal (ULN) who achieve ALT normalization
Time frame: From baseline through end of study (Week 96)
Proportion of patients with drug-resistant mutations
Time frame: From baseline through end of study (Week 96)
Proportion of participants with treatment-emergent adverse events (TEAEs)
Proportion of participants who experience treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events leading to discontinuation of study treatment.
Time frame: From first dose (Day 1) through end of study (Week 96)
Proportion of participants with detectable anti-drug antibody (ADA) to AHB-137 and corresponding ADA titers
Time frame: From baseline through end of study (Week 96)
Area under the plasma concentration-time curve (AUC) of AHB-137
Time frame: From first dose (Day 1) through end of pharmacokinetic sampling (Week 48)
Concentration at the end of the dosing interval (Ct) of AHB-137
Time frame: From first dose (Day 1) through end of pharmacokinetic sampling (Week 48)
Maximum observed plasma concentration (Cmax) of AHB-137
Time frame: From first dose (Day 1) through end of pharmacokinetic sampling (Week 48)
Time to maximum observed plasma concentration (Tmax) of AHB-137
Time frame: From first dose (Day 1) through end of pharmacokinetic sampling (Week 48)
Apparent plasma clearance (CL/F) of AHB-137
Time frame: From first dose (Day 1) through end of pharmacokinetic sampling (Week 48)
Population Pharmacokinetic and Exposure-Response Analyses of AHB-137
Population pharmacokinetic modeling of AHB-137, including covariate analysis and assessment of exposure-response relationships for pharmacodynamic, efficacy, and safety endpoints.
Time frame: From first dose (Day 1) through end of study (Week 96)