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

April 27, 2023 updated by: Aligos Therapeutics

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)

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

336

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Fitzroy, Victoria, Australia, 3065
      • Footscray, Victoria, Australia, 3011
  • China
    • Chongqing
      • Chongqing, Chongqing, China, 400016
        • Recruiting
        • The Second Affiliated Hospital of Chongqing Medical University
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China
        • Recruiting
        • NanFang Hospital of Southern Medical University
    • Jilin
      • Changchun, Jilin, China, 130021
        • Recruiting
        • The first hospital of Jilin University
  • Hong Kong
      • Hong Kong, Hong Kong
        • Recruiting
        • Queen Mary Hospital
      • Shatin, Hong Kong
  • Mauritius
      • Quatre Bornes, Mauritius, 72218
  • Moldova, Republic of
      • Chisinau, Moldova, Republic of
        • Recruiting
        • PMSI Republican Clinical Hospital "T. Mosneaga", ARENSIA Exploratory Medicine Phase I Unit
  • New Zealand
      • Auckland, New Zealand
        • Recruiting
        • ACS
  • United Kingdom
      • London, United Kingdom
        • Recruiting
        • King's College Hospital
      • London, United Kingdom, SW170RE

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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 4 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 4 weeks
Drug: Placebo
Single or multiple doses of Placebo
Active Comparator: Entecavir in combination with ALG-000184
Drug: ALG-000184
Single or multiple doses of ALG-000184
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]
Time Frame: up to 8 days for Part 1
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]
Time Frame: up to 21 days for Part 2
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]
Time Frame: up to 112 days for Part 3
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]
Time Frame: Up to 336 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)
Up to 336 days for parts 4 & 5

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Plasma Concentration [Cmax]
Time Frame: Predose up to 343 Days
Pharmacokinetic parameters of ALG-000184 in plasma
Predose up to 343 Days
Area under the concentration time curve [AUC]
Time Frame: Predose up to 343 Days
Pharmacokinetic parameters of ALG-000184 in plasma
Predose up to 343 Days
Time to maximum plasma concentration [Tmax]
Time Frame: Predose up to 343 Days
pharmacokinetic parameters of ALG-000184 in plasma
Predose up to 343 Days
Half-time [t1/2]
Time Frame: Predose up to 343 Days
Pharmacokinetic parameters of ALG-000184 in plasma
Predose up to 343 Days
Minimum Plasma Concentration [Cmin]
Time Frame: Predose up to 343 Days
Pharmacokinetic parameters of ALG-000184 in plasma
Predose up to 343 Days
Change in HBV DNA from baseline through Day 392 in Multiple Dose HBV Infected Patients
Time Frame: Screening up to Day 392
Screening up to Day 392

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Aligos Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 22, 2020

Primary Completion (Anticipated)

November 24, 2023

Study Completion (Anticipated)

June 1, 2024

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 (Actual)

April 28, 2023

Last Update Submitted That Met QC Criteria

April 27, 2023

Last Verified

November 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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