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

NCT04536337 | Completed Phase 1 DMC

• 1 other identifier: ALG-000184-201
• Study Type: interventional
• Target: 165
• Locations: 6 countries
• Sites: 10

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

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (6)

• Maximum Plasma Concentration [Cmax]

  Predose up to763 Days

• Area under the concentration time curve [AUC]

  Predose up to 763 Days

• Time to maximum plasma concentration [Tmax]

  Predose up to 763 Days

• Half-time [t1/2]

  Predose up to 763 Days

• Minimum Plasma Concentration [Cmin]

  Predose up to 763 Days

Study Arms (5)

ALG-000184

EXPERIMENTAL

Oral tablet(s) of ALG-000184 in HV or CHB subjects once daily for up to 96 weeks

Drug: ALG-000184

Placebo

PLACEBO COMPARATOR

Oral tablet(s) of placebo in HV or CHB subjects once daily for up to 12 weeks

Drug: Placebo

Entecavir in combination with ALG-000184

ACTIVE COMPARATOR

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; Drug: Entecavir

Placebo plus Entecavir

ACTIVE COMPARATOR

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; Drug: Entecavir

Open-label ALG-000184 plus Entecavir

EXPERIMENTAL

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; Drug: Entecavir

Interventions

ALG-000184 DRUG

Single or multiple doses of ALG-000184

ALG-000184; Entecavir in combination with ALG-000184; Placebo plus Entecavir

Placebo DRUG

Single or multiple doses of Placebo

Open-label ALG-000184 plus Entecavir; Placebo

Entecavir DRUG

multiple doses of Entecavir

Entecavir in combination with ALG-000184; Open-label ALG-000184 plus Entecavir; Placebo plus Entecavir

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female subjects must have a negative serum pregnancy test at screening
• Subjects must have a 12-lead electrocardiogram (ECG) that meets the protocol criteria
• Male or female between 18 and 55 years of age, extremes included.
• 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:
• All of the Following criteria apply to Part 3 at screening:
• Subjects must be 18 to 65 years of age, extremes included.
• CHB subjects must have a BMI of 18.0 to 35.0 kg/m2, extremes included.
• 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:
• Subjects must be 18 to 65 years of age, extremes included.
• Subjects must have a BMI of 18.0 to 35.0 kg/m2, extremes included
• Subjects must be HBeAg positive (HBeAg ≥LLOQ and HBeAb negative)
• Subjects enrolled in Part 4 Cohort A and B must have a history of Chronic Hepatitis B
• \. Subjects must have ALT and AST must have ≤1.2×ULN or ≤5×ULN

You may not qualify if:

• 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
• 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.
• Subjects with a history of clinically significant drug allergy
• Subject with a current history of clinically significant (as determined by investigator) skin disease requiring intermittent or chronic treatment
• Excessive use of alcohol, defined as regular consumption of ≥14 standard drinks/week for women and ≥21 standard drinks/week for men
• Subjects with Hepatitis A, B, C, D, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection
• Unwilling to abstain from alcohol use for 48 hours prior to start of dosing through end of study follow up.
• Positive alcohol or cotinine test at screening and Day -1.
• 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).
• Subjects who are positive for anti-HBs antibodies.
• For HBeAg-positive subjects, they should be negative for anti-HBe antibodies (Parts 4 and 5)
• 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).
• History or current evidence of cirrhosis.
• Subjects with liver fibrosis that is classified as Metavir Score ≥F3 liver disease
• Subjects with signs of hepatocellular carcinoma

Sponsors & Collaborators

• Aligos Therapeutics: lead

Study Sites (10)

Saint Vincent's Hospital Melbourne

Fitzroy, Victoria, 3065, Australia

Location

Western Health

Footscray, Victoria, 3011, Australia

Location

The Second Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

Location

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Prince of Wales

Shatin, Hong Kong

Location

CAP Research

Quatre Bornes, Mauritius, 72218, Mauritius

Location

PMSI Republican Clinical Hospital "T. Mosneaga", ARENSIA Exploratory Medicine Phase I Unit

Chisinau, Moldova

Location

ACS

Auckland, New Zealand

Location

Related Publications (3)

• Yuen MF, Agarwal K, Jucov A, Hou J, Niu J, Ding Y, Haceatrean A, Liang X, Xu J, Wu M, Le K, Lin TI, Blatt L, Chanda S, Fry J, Gane E. ALG-000184 (pevifoscorvir sodium) monotherapy in participants with chronic HBV infection: a phase 1, multicentre, randomised, dose escalation trial. Lancet Gastroenterol Hepatol. 2026 Jan 16:S2468-1253(25)00293-6. doi: 10.1016/S2468-1253(25)00293-6. Online ahead of print.

  PMID: 41554267 DERIVED

• 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.

  PMID: 41268712 DERIVED

• 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.

  PMID: 34280012 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: August 28, 2020
• First Posted: September 2, 2020
• Study Start: October 22, 2020
• Primary Completion: June 16, 2025
• Study Completion: June 16, 2025
• Last Updated: November 21, 2025

Record last verified: 2025-11

Locations

AU (2); MA (1); MO (1); NZ (1); CN (3); HK (2)