Chronic Hepatitis B
Conditions
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.
Interventions
DRUGALG-000184
Single or multiple doses of ALG-000184
DRUGPlacebo
Single or multiple doses of Placebo
DRUGEntecavir
multiple doses of Entecavir
Sponsors
Aligos Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This is a parallel-group study with several parts. In Parts 1-3, participants are randomized in a 4:1 ratio to receive either ALG-000184 or matching placebo. In Part 4, participants are randomized in a 4:1 ratio to receive either ALG-000184 plus entecavir or placebo plus entecavir. In Part 5, all participants receive open-label ALG-000184 plus entecavir. The study follows a dose-escalation design where doses are increased across cohorts based on safety and pharmacokinetic data from previous cohorts. Each participant remains in their assigned treatment group throughout their participation in the study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
for All Subjects: 1. Female subjects must have a negative serum pregnancy test at screening 2. Subjects must have a 12-lead electrocardiogram (ECG) that meets the protocol criteria Inclusion Criteria for Healthy Volunteers: In addition to inclusion criteria 1-2, the following inclusion criteria also apply to HV's (Parts 1 and 2) 3. Male or female between 18 and 55 years of age, extremes included. 4. Subjects must have a body mass index (BMI; weight in kg divided by the square of height in meters) of 18.0 to 32.0 kg/m2, extremes included. CHB Subjects: In addition to inclusion criteria 1-4, the following inclusion criteria also apply to CHB subjects: All of the Following criteria apply to Part 3 at screening: 5 .Subjects must be 18 to 65 years of age, extremes included. 6.CHB subjects must have a BMI of 18.0 to 35.0 kg/m2, extremes included. 7.CHB subjects who at screening, have not received treatment with an approved or investigational medicine, or have never received treatment with HBV antiviral medicines All of the following criteria apply to Part 4 Cohorts A & B, unless otherwise specified, at Screening: 8.Subjects must be 18 to 65 years of age, extremes included. 9.Subjects must have a BMI of 18.0 to 35.0 kg/m2, extremes included 10.Subjects must be HBeAg positive (HBeAg ≥LLOQ and HBeAb negative) 11.Subjects enrolled in Part 4 Cohort A and B must have a history of Chronic Hepatitis B 12\. Subjects must have ALT and AST must have ≤1.2×ULN or ≤5×ULN All of the following criteria apply to Part 5 at Screening 13.Subjects must be 18 to 65 years of age, extremes included. 14\. Subjects have a BMI of 17.0 to 35.0 kg/m2, extremes included 15.Subjects could belong to any of the following treatment categories: treatment naïve (TN), currently not treated (CNT) , virologically suppressed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | up to 8 days for Part 1 | The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 | — |
| Time to maximum plasma concentration [Tmax] | Predose up to 763 Days | pharmacokinetic parameters of ALG-000184 in plasma |
Countries
Australia, China, Hong Kong, Mauritius, Moldova, New Zealand
Outcome results
None listed