The goal of this clinical trial is to learn if ALG-000184 is safe, well-tolerated, and works to treat chronic hepatitis B virus (HBV) infection. The main questions it aims to answer are: Is ALG-000184 safe and well-tolerated when given alone or with entecavir (a standard HBV treatment)? Does ALG-000184 reduce HBV viral levels in the blood of patients with chronic hepatitis B? How does the body process ALG-000184 (pharmacokinetics)? Researchers will compare ALG-000184 to placebo (a look-alike substance that contains no drug) to see if ALG-000184 works better at reducing hepatitis B viral markers. The study has five parts: Parts 1 and 2: Healthy volunteers will receive single or multiple doses of ALG-000184 or placebo Part 3: Patients with chronic hepatitis B will receive ALG-000184 or placebo daily for 28 days Part 4: Patients with chronic hepatitis B will receive ALG-000184 or placebo combined with entecavir for 12 weeks (may be extended up to 96 weeks) Part 5: Additional groups of patients with chronic hepatitis B will receive ALG-000184 with entecavir for 12 weeks (may be extended up to 96 weeks) Participants will: Take study medication orally as directed Visit the clinic regularly for blood tests, physical examinations, and other safety assessments Have their HBV viral markers measured to determine if the treatment is working
ALG-000184-201 is a Phase 1, double-blind, randomized, placebo-controlled study evaluating ALG-000184, a novel capsid assembly modulator (CAM) targeting hepatitis B virus (HBV). ALG-000184 is a prodrug that is converted to ALG-001075, a Class E CAM that inhibits HBV replication through two mechanisms: (1) blocking pregenomic RNA encapsidation, and (2) preventing the formation and transcription of covalently closed circular DNA (cccDNA). The study employs a sequential approach, beginning with single-ascending dose (SAD) and multiple-ascending dose (MAD) evaluations in healthy volunteers, then progressing to monotherapy assessments in chronic hepatitis B (CHB) subjects, and finally testing combination therapy with entecavir. A Study Review Committee (SRC) oversees safety throughout the trial and determines dose escalation based on predefined criteria. Each cohort in Parts 1-3 includes a 4:1 (ALG-000184:placebo) randomization ratio, while Parts 4-5 include extended treatment durations to evaluate longer-term efficacy and safety. The study includes comprehensive pharmacokinetic assessments and extensive virologic evaluations (HBV DNA, HBV RNA, HBsAg, HBeAg, HBcrAg, and resistance monitoring). An ALT Flare Committee specifically reviews and manages liver-related safety events. Part 4 focuses on HBeAg-positive subjects to explore potential HBsAg declines, as the secondary mechanism of action of ALG-000184 may be more pronounced in subjects with higher cccDNA levels. The trial includes provisions for extending treatment duration up to 96 weeks based on emerging safety and efficacy data.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
165
Single or multiple doses of ALG-000184
Single or multiple doses of Placebo
multiple doses of Entecavir
Saint Vincent's Hospital Melbourne
Fitzroy, Victoria, Australia
Western Health
Footscray, Victoria, Australia
The Second Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, China
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, China
The First Hospital of Jilin University
Changchun, Jilin, China
Queen Mary Hospital
Hong Kong, Hong Kong
Prince of Wales
Shatin, Hong Kong
CAP Research
Quatre Bornes, Mauritius, Mauritius
PMSI Republican Clinical Hospital "T. Mosneaga", ARENSIA Exploratory Medicine Phase I Unit
Chisinau, Moldova
ACS
Auckland, New Zealand
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1
Time frame: up to 8 days for Part 1
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1
Time frame: up to 21 days for Part 2
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1
Time frame: up to 112 days for Part 3
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1 of ALG-184 in combination with Entecavir (Parts 4 and 5)
Time frame: Up to 756 days for parts 4 & 5
Maximum Plasma Concentration [Cmax]
Pharmacokinetic parameters of ALG-000184 in plasma
Time frame: Predose up to763 Days
Area under the concentration time curve [AUC]
Pharmacokinetic parameters of ALG-000184 in plasma
Time frame: Predose up to 763 Days
Time to maximum plasma concentration [Tmax]
pharmacokinetic parameters of ALG-000184 in plasma
Time frame: Predose up to 763 Days
Half-time [t1/2]
Pharmacokinetic parameters of ALG-000184 in plasma
Time frame: Predose up to 763 Days
Minimum Plasma Concentration [Cmin]
Pharmacokinetic parameters of ALG-000184 in plasma
Time frame: Predose up to 763 Days
Change in HBV DNA from baseline through Day 812 in Multiple Dose HBV Infected Patients
Time frame: Screening up to Day 812
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