The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of AHB-137 subcutaneous injection in healthy volunteers and in chronic hepatitis B (CHB) patients after single and multiple doses. In addition, the study will evaluate the initial antiviral efficacy of AHB-137 in CHB patients following a multiple dosing regimen.
This is a first-in-human study of AHB-137, consisting of four parts. Parts A and B are randomized, double-blinded, placebo-controlled studies designed to assess the safety, tolerability, pharmacokinetics of AHB-137 following subcutaneous injection in healthy volunteers at a 6:2 ratio of AHB-137 to placebo. Part A is a single-ascending dose (SAD) study, and Part B is a single-ascending dose (SAD) study, and Part B is a multiple dose (MD) study. Part C is an open label MD study with up to 6 CHB patients. Part D is a double blinded study in CHB patients at a 4:1 ratio to receive AHB-137 or placebo. Study advancement to subsequent parts/cohorts will require satisfactory interim reviews of available cumulative safety data by the Safety Review Committees (SRC), using the safety criteria and review procedures described in the protocol.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
64
AHB-137 will be administered
Placebo will be administered
Stanford Medicine
Redwood City, California, United States
University of Maryland Baltimore
Baltimore, Maryland, United States
NYU Langone Health
New York, New York, United States
American Research Corporation
Houston, Texas, United States
Proportion of Participants With Treatment-Emergent Adverse Events (TEAEs) in Healthy Volunteers
Time frame: Up to 30 days for SAD, up to 113 days for MD
Proportion of Participants With Treatment-Emergent Adverse Events (TEAEs) in CHB patients
Time frame: Up to 204 days for MD
The anti-HBV efficacy of AHB-137: evaluate the change in serum HBsAg (log10 IU/mL) from baseline.
Time frame: Up to 204 days
The anti-HBV efficacy of AHB-137: evaluate the expression of HBsAb in serum.
Time frame: Up to 204 days
The pharmacokinetic profile of AHB-137: the maximum observed plasma concentration (Cmax) of AHB-137
Time frame: Up to 30 days for SAD; up to 204 days for MD
The pharmacokinetic profile of AHB-137: time of observed maximal concentration (Tmax) of AHB-137
Time frame: Up to 30 days for SAD; up to 204 days for MD
The pharmacokinetic profile of AHB-137: areas under the concentration time curve (AUC) of AHB-137
Time frame: Up to 30 days for SAD; up to 204 days for MD
The pharmacokinetic profile of AHB-137: mean residence time (MRT) of AHB-137
Time frame: Up to 30 days for SAD; up to 204 days for MD
The pharmacokinetic profile of AHB-137: terminal half-life (t1/2) of AHB-137
Time frame: Up to 30 days for SAD; up to 204 days for MD
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Queen Mary Hospital
Hong Kong, Hong Kong
New Zealand Clinical Research
Grafton, Auckland, New Zealand
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung, Taiwan, Taiwan
E-DA Hospital
Kaohsiung, Taiwan, Taiwan
Chia-Yi Christian Hospital
Chiayi City, Taiwan
The pharmacokinetic profile of AHB-137: apparent subcutaneous plasma clearance (CL/F) of AHB-137
Time frame: Up to 30 days for SAD; up to 204 days for MD
The pharmacokinetic profile of AHB-137: amount of AHB-137 excreted in urine (Ae)
Time frame: Day 1-4 for SAD; Day 1-4 and Day 22-25 for MD
The pharmacokinetic profile of AHB-137: renal clearance (CLr) of AHB-137
Time frame: Day 1-4 for SAD; Day 1-4 and Day 22-25 for MD