This is a randomized, double-blind, placebo-controlled Phase I dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of multiple ascending doses (120 mg, 240 mg, 480 mg SC, QW×5) of HH-006 in untreated chronic HBV patients. Each cohort includes 12 participants (9 active, 3 placebo), with dose progression approved by a Safety Review Committee. Participants are monitored through 24 weeks post-dose. The study design allows for adjustments based on emerging data.
This is a randomized, double-blind, placebo-controlled, multiple-dose escalation Phase I clinical study. The study aims to evaluate the safety, tolerability, pharmacokinetic profile, and preliminary antiviral activity of multiple doses (120 mg QW, 240 mg QW, 480 mg QW, administered subcutaneously (S.C.) once weekly (QW) for 5 doses) in chronic hepatitis B virus (HBV) infected participants who are not receiving anti-HBV treatment, are HBeAg-negative or positive, have HBV DNA ≥ 100 IU/mL, 100 IU/mL \< HBsAg \< 5000 IU/mL, and ALT ≤ 5 × ULN. Each dose cohort plans to enroll 12 participants, enrolled in batches according to the dose escalation principle. Participants will be randomized to receive either HH-006 (N=9) or placebo (N=3) for a repeated-dose (5 doses) tolerability and pharmacokinetic study. Dosing for the next cohort will commence only after all 12 participants in the current dose cohort have completed the safety assessment up to 14 days post-last dose (Week 7, Day 43) and after review and approval by the Safety Review Committee. The currently planned maximum dose for escalation is 480 mg QW. Each participant is planned to be followed up for 24 weeks after the last dose to assess the safety, tolerability, PK, immunogenicity, and preliminary antiviral activity of HH-006 in participants with chronic HBV infection. During the study, adjustments to the maximum dose, dosing regimen, blood sampling time points, and follow-up duration may be made based on the accumulating data obtained during the study. Throughout the study, participants' safety indicators and virologic parameters will be closely monitored to evaluate the safety and antiviral activity of HH-006.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
36
120 mg, 240 mg, 480 mg subcutaneous QW, 5 doses
1 mL, 2 mL, 4 mL subcutaneous QW, 5 doses
NanFang Hospital of Southern Medical University
Guangzhou, Guangdong, China
The Affiliated Panyu Central Hospital of Guangzhou Medical University
Guangzhou, Guangdong, China
The Eighth Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, China
Incidence of adverse events (AEs) and serious adverse events (SAEs)
Number of subjects with adverse events (AEs) and serious adverse events (SAEs) assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: up to 24 weeks follow-up
Clinically significant abnormalities
Number of subjects with clinically significant abnormalities in vital signs, electrocardiogram (ECG), and laboratory parameters graded by CTCAE v5.0.
Time frame: up to 24 weeks follow-up
Area Under the Plasma Concentration Versus Time Curve (AUC)
AUC of HH-006 in plasma
Time frame: up to 24 weeks follow-up
Maximum Plasma Concentration (Cmax)
Cmax of HH-006 in plasma
Time frame: up to 24 weeks follow-up
Time to Reach Maximum Plasma Concentration (Tmax)
Tmax of HH-006 in plasma
Time frame: up to 24 weeks follow-up
Apparent Terminal Elimination Half-life (T1/2)
T1/2 of HH-006 in plasma
Time frame: up to 24 weeks follow-up
Apparent Plasma Clearance (CL/F)
CL/F of HH-006 in plasma
Time frame: up to 24 weeks follow-up
Immunogenicity: ADA
Time frame: up to 24 weeks follow-up
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Antiviral Activity: Change in HBV DNA levels from baseline (at each study time point); Change in HBsAg levels from baseline (at each study time point)
Time frame: up to 24 weeks follow-up