A Study of ALG-000184 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects
- Conditions
- Chronic Hepatitis B
- Interventions
- Registration Number
- NCT04536337
- Lead Sponsor
- Aligos Therapeutics
- Brief Summary
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
- Detailed Description
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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 165
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ALG-000184 ALG-000184 Oral tablet(s) of ALG-000184 in HV or CHB subjects once daily for up to 96 weeks Placebo Placebo Oral tablet(s) of placebo in HV or CHB subjects once daily for up to 12 weeks Entecavir in combination with ALG-000184 ALG-000184 Oral tablet(s) of ALG-000184 in combination with Entecavir in CHB subjects once or twice daily for up to 96 weeks Entecavir in combination with ALG-000184 Entecavir Oral tablet(s) of ALG-000184 in combination with Entecavir in CHB subjects once or twice daily for up to 96 weeks Placebo plus Entecavir ALG-000184 Oral tablet(s) of matching placebo in combination with Entecavir in CHB subjects once daily for 12 weeks, with option to switch to open-label ALG-000184 plus Entecavir for up to 96 weeks (Part 4). Placebo plus Entecavir Entecavir Oral tablet(s) of matching placebo in combination with Entecavir in CHB subjects once daily for 12 weeks, with option to switch to open-label ALG-000184 plus Entecavir for up to 96 weeks (Part 4). Open-label ALG-000184 plus Entecavir Placebo Open-label oral tablet(s) of ALG-000184 in combination with Entecavir in CHB subjects once daily for up to 96 weeks (Part 5) Open-label ALG-000184 plus Entecavir Entecavir Open-label oral tablet(s) of ALG-000184 in combination with Entecavir in CHB subjects once daily for up to 96 weeks (Part 5)
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Up to 756 days for parts 4 & 5 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)
- Secondary Outcome Measures
Name Time Method Maximum Plasma Concentration [Cmax] Predose up to763 Days Pharmacokinetic parameters of ALG-000184 in plasma
Area under the concentration time curve [AUC] Predose up to 763 Days Pharmacokinetic parameters of ALG-000184 in plasma
Time to maximum plasma concentration [Tmax] Predose up to 763 Days pharmacokinetic parameters of ALG-000184 in plasma
Half-time [t1/2] Predose up to 763 Days Pharmacokinetic parameters of ALG-000184 in plasma
Minimum Plasma Concentration [Cmin] Predose up to 763 Days Pharmacokinetic parameters of ALG-000184 in plasma
Change in HBV DNA from baseline through Day 812 in Multiple Dose HBV Infected Patients Screening up to Day 812
Trial Locations
- Locations (10)
Saint Vincent's Hospital Melbourne
🇦🇺Fitzroy, Victoria, Australia
Western Health
🇦🇺Footscray, Victoria, Australia
The Second Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, Chongqing, 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
PMSI Republican Clinical Hospital "T. Mosneaga", ARENSIA Exploratory Medicine Phase I Unit
🇲🇩Chisinau, Moldova, Republic of
ACS
🇳🇿Auckland, New Zealand
Saint Vincent's Hospital Melbourne🇦🇺Fitzroy, Victoria, Australia