The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of AHB-137 subcutaneous injection in healthy participants after single and multiple doses, and evaluate the preliminary efficacy of AHB-137 in CHB participants after up to 24 weeks of treatment as a proof-of-concept.
This study is a three-part study of AHB-137, including Part Ia, Part Ib and Part IIa. Part Ia evaluates the safety, tolerability, pharmacokinetics of AHB-137 following single-ascending doses (SAD) and multiple-ascending doses (MAD) in healthy participants. Part Ib is a multiple-dose study to assess the safety, tolerability, pharmacokinetics, and initial efficacy of AHB-137 in CHB participants following weekly dosing for 4 weeks with two loading doses in the first two weeks. Part IIa is a multiple-dose study to evaluate the preliminary efficacy, safety and pharmacokinetics of AHB-137 in CHB participants following weekly dosing for 24 weeks with two loading doses in the first two weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
129
AHB-137 injection will be administered subcutaneously.
Placebo will be administered subcutaneously.
The Second Affiliated Hospital of Chongqing Medical University
Chongqing, China
Nanfang Hospital, Southern Medical University
Guangzhou, China
The First Hospital of Jilin University
Jilin City, China
Number of healthy participants with TEAEs, SAEs
Time frame: Up to 30 days for SAD; up to 113 days for MAD
Number of healthy participants with clinically significant changes in laboratory parameters
Time frame: Up to 30 days for SAD; up to 113 days for MAD
Number of healthy participants with clinically significant changes in vital signs
Time frame: Up to 30 days for SAD; up to 113 days for MAD
Number of healthy participants with clinically significant changes in ECG
Time frame: Up to 30 days for SAD; up to 113 days for MAD
Number of healthy participants with ADA
Time frame: Up to 30 days for SAD; up to 113 days for MAD
The pharmacokinetic profile of AHB-137 in healthy participants: the Cmax of AHB-137
Time frame: Up to 30 days for SAD; up to 113 days for MAD
The pharmacokinetic profile of AHB-137 in healthy participants: Tmax of AHB-137
Time frame: Up to 30 days for SAD; up to 113 days for MAD
The pharmacokinetic profile of AHB-137 in healthy participants: AUC of AHB-137
Time frame: Up to 30 days for SAD; up to 113 days for MAD
The pharmacokinetic profile of AHB-137 in healthy participants: t1/2 of AHB-137
Time frame: Up to 30 days for SAD; up to 113 days for MAD
Number of CHB participants with TEAEs, SAEs
Time frame: Up to 113 days for Ib
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Number of CHB participants with clinically significant changes in laboratory parameters
Time frame: Up to 113 days for Ib
Number of CHB participants with clinically significant changes in vital signs
Time frame: Up to 113 days for Ib
Number of CHB participants with clinically significant changes in ECG
Time frame: Up to 113 days for Ib
Proportion of participants achieving HBsAg lower than LLOQ (0.05 IU/mL) and HBV DNA lower than LLOQ at the end of treatment with AHB-137, regardless of whether HBsAg seroconversion is observed
Time frame: At week 24 for IIa
The anti-HBV efficacy of AHB-137 in CHB participants: evaluate the serum levels of HBV DNA, HBsAg, HBV RNA, HBsAb, HBeAb
Time frame: Up to 113 days for Ib; Up to 72 weeks for IIa
Evaluate the serum levels of sensitive HBsAg (LLOQ ≤0.005 IU/mL) and HBcrAg.
Time frame: Up to 72 weeks for IIa
The pharmacokinetic profile of AHB-137 in CHB participants: the Cmax of AHB-137
Time frame: up to 113 days for Ib; Up to 48 weeks for IIa
The pharmacokinetic profile of AHB-137 in CHB participants: Tmax of AHB-137
Time frame: up to 113 days for Ib; Up to 48 weeks for IIa
The pharmacokinetic profile of AHB-137 in CHB participants: AUC of AHB-137
Time frame: up to 113 days for Ib; Up to 48 weeks for IIa
The pharmacokinetic profile of AHB-137 in CHB participants: t1/2 of AHB-137
Time frame: up to 113 days for Ib; Up to 48 weeks for IIa
Number of CHB participants with ADA
Time frame: Up to113 days for Ib; Up to 48 weeks for IIa
Number of CHB participants with TEAEs, SAEs
Time frame: Up to 72 weeks for IIa
Number of CHB participants with clinically significant changes in laboratory parameters, ECG, and vital signs
Time frame: Up to 72 weeks for IIa
Proportion of CHB participants achieving HBsAg lower than LLOQ and HBV DNA lower than LLOQ during or after 24-week treatment, regardless of whether HBsAg seroconversion is observed
Time frame: Up to 72 weeks for IIa
Proportion of CHB participants meeting the discontinuation criteria for NA treatment
Time frame: At 48 weeks for IIa
Sequencing of the Viral DNA and/or viral RNA analysis for detection of drug resistance in the target region of AHB-137
Time frame: Up to 113 days for Ib; Up to 72 weeks for IIa