A Study of ALG-000184 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects

A Phase 1, Double-Blind, Randomized, Placebo-Controlled, First-in-Human Study of Orally Administered ALG-000184 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single-Ascending Doses (Part 1) and Multiple-Ascending Doses in Healthy Volunteers (Part 2), and Multiple Doses in Subjects With Chronic Hepatitis B (Part 3)

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

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Placebo; Drug: ALG-000184; Drug: Entecavir

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.

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Fitzroy, Victoria, Australia, 3065
      • Saint Vincent's Hospital Melbourne
    • Footscray, Victoria, Australia, 3011
      • Western Health
• China
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400016
      • The Second Affiliated Hospital of Chongqing Medical University
  • Guangdong
    • Guangzhou, Guangdong, China
      • Nanfang Hospital of Southern Medical University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
  • Shatin, Hong Kong
    • Prince of Wales
• Mauritius
  • Mauritius
    • Quatre Bornes, Mauritius, Mauritius, 72218
      • CAP Research
• Moldova
  • Chisinau, Moldova
    • PMSI Republican Clinical Hospital "T. Mosneaga", ARENSIA Exploratory Medicine Phase I Unit
• New Zealand
  • Auckland, New Zealand
    • ACS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Exclusion Criteria

Exclusion Criteria for All Subjects:

1. Subjects with any previous or current illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject, or pose an additional risk in administering study drug to the subject, or that could prevent, limit, or confound the protocol specified assessments or study results' interpretation
2. Subjects with a past history of cardiac arrhythmias, risk factors for Torsade de Pointes syndrome (e.g., hypokalemia, family history of long QT syndrome, or history of clinical evidence at screening of significant or unstable cardiac disease etc.
3. Subjects with a history of clinically significant drug allergy
4. Subject with a current history of clinically significant (as determined by investigator) skin disease requiring intermittent or chronic treatment
5. Excessive use of alcohol, defined as regular consumption of ≥14 standard drinks/week for women and ≥21 standard drinks/week for men

6. Subjects with Hepatitis A, B, C, D, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection

   Exclusion Criteria for Healthy Volunteers (Parts 1 and 2):

   In addition to exclusion criteria 1-6, the following exclusion criteria also apply to HV's (Parts 1 and 2)

7. Unwilling to abstain from alcohol use for 48 hours prior to start of dosing through end of study follow up.
8. Positive alcohol or cotinine test at screening and Day -1.

9. Subjects with renal dysfunction (e.g., estimated creatinine clearance <90 mL/min/1.73 m2at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula).

   Exclusion Criteria for CHB Subjects (Parts 3, 4, and 5):

   All exclusion criteria listed above for healthy volunteers apply also to CHB subjects, except for exclusion Criteria 9 (requirement relative to cotinine).All the following exclusion criteria apply to Parts 3, 4, and 5, unless otherwise specified.

10. Subjects who are positive for anti-HBs antibodies.
11. For HBeAg-positive subjects, they should be negative for anti-HBe antibodies (Parts 4 and 5)
12. Subject with any history or current evidence of hepatic decompensation such as: variceal bleeding, spontaneous bacterial peritonitis, ascites, hepatic encephalopathy, or active jaundice (within the last year).
13. History or current evidence of cirrhosis.
14. Subjects with liver fibrosis that is classified as Metavir Score ≥F3 liver disease
15. Subjects with signs of hepatocellular carcinoma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALG-000184; Oral tablet(s) of ALG-000184 in HV or CHB subjects once daily for up to 96 weeks	Drug: ALG-000184; Single or multiple doses of ALG-000184
Placebo Comparator: Placebo; Oral tablet(s) of placebo in HV or CHB subjects once daily for up to 12 weeks	Drug: Placebo; Single or multiple doses of Placebo
Active Comparator: Entecavir in combination with ALG-000184; Oral tablet(s) of ALG-000184 in combination with Entecavir in CHB subjects once or twice daily for up to 96 weeks	Drug: ALG-000184; Single or multiple doses of ALG-000184; Drug: Entecavir; multiple doses of Entecavir
Active Comparator: Placebo plus 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).	Drug: ALG-000184; Single or multiple doses of ALG-000184; Drug: Entecavir; multiple doses of Entecavir
Experimental: Open-label ALG-000184 plus 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)	Drug: Placebo; Single or multiple doses of Placebo; Drug: Entecavir; multiple doses of Entecavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	The number and severity of treatment emergent adverse events as assessed by DAIDS v2.1	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	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	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)	Up to 756 days for parts 4 & 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration [Cmax]	Pharmacokinetic parameters of ALG-000184 in plasma	Predose up to763 Days
Area under the concentration time curve [AUC]	Pharmacokinetic parameters of ALG-000184 in plasma	Predose up to 763 Days
Time to maximum plasma concentration [Tmax]	pharmacokinetic parameters of ALG-000184 in plasma	Predose up to 763 Days
Half-time [t1/2]	Pharmacokinetic parameters of ALG-000184 in plasma	Predose up to 763 Days
Minimum Plasma Concentration [Cmin]	Pharmacokinetic parameters of ALG-000184 in plasma	Predose up to 763 Days
Change in HBV DNA from baseline through Day 812 in Multiple Dose HBV Infected Patients		Screening up to Day 812

Collaborators and Investigators

• Sponsor: Aligos Therapeutics

Publications and helpful links

General Publications

• Li C, Wu M, Zhang H, Mai J, Yang L, Ding Y, Niu J, Mao J, Wu W, Zhang D, Tang Y, Yan W. Safety, Tolerability, and Pharmacokinetics of the Novel Hepatitis B Virus Capsid Assembly Modulator GST-HG141 in Healthy Chinese Subjects: a First-in-Human Single- and Multiple-Dose Escalation Trial. Antimicrob Agents Chemother. 2021 Sep 17;65(10):e0122021. doi: 10.1128/AAC.01220-21. Epub 2021 Jul 19.
• Gane E, Schwabe C, Wu M, Lin TI, Blatt L, Fry J, Chanda S, Le K. A Phase 1 study of the safety, tolerability, and pharmacokinetics of ALG-000184 (pevifoscorvir sodium), a novel Class E capsid assembly modulator, in healthy participants. Antivir Ther. 2025 Dec;30(6):13596535251392955. doi: 10.1177/13596535251392955. Epub 2025 Nov 21.

Study record dates

Study Major Dates

• Study Start (Actual): October 22, 2020
• Primary Completion (Actual): June 16, 2025
• Study Completion (Actual): June 16, 2025

Study Registration Dates

• First Submitted: August 28, 2020
• First Submitted That Met QC Criteria: August 28, 2020
• First Posted (Actual): September 2, 2020

Study Record Updates

• Last Update Posted (Estimated): November 21, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis; Pathological Conditions, Signs and Symptoms; Hepatitis B; Hepatitis B, Chronic; Anti-Infective Agents; Antiviral Agents; entecavir
• Other Study ID Numbers: ALG-000184-201

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No