A Study of ALG-020572 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Doses in Healthy Volunteers and Multiple Doses in CHB Subjects

A Phase 1, Double-Blind, Randomized, Placebo-Controlled, First-in-Human Study of Subcutaneously Administered ALG-020572 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Ascending Doses in Healthy Volunteers (Part 1) and Multiple Doses in Subjects With Chronic Hepatitis B (Part 2)

A Randomized Study of ALG-020572 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single and Multiple Doses in Healthy Volunteers and CHB Subjects

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: Placebo; Drug: ALG-020572

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • Auckland Clinical Studies
• United Kingdom
  • London, United Kingdom
    • King's College Hospital
  • London, United Kingdom
    • St George's University of London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria for Healthy Subjects:

1. Male and Female between 18 and 55 years old
2. Female subjects must have a negative serum pregnancy test at screening
3. BMI 18.0 to 32.0 kg/m^2
4. Subjects must have a 12-lead ECG that meets protocol criteria

Inclusion Criteria for CHB Subjects:

1. Male and Female between 18 and 75 years old
2. Female subjects must have a negative serum pregnancy test at screening
3. BMI 18.0 to 35.0 kg/m^2
4. For virally suppressed subjects, must be currently receiving HBV NA treatment for ≥6 months prior to screening. For currently not treated or treatment naïve subjects, must have never received treatment OR have not been on treatment within 6 months prior to randomization
5. Subjects must have a 12-lead ECG that meets protocol criteria

Exclusion Criteria for Healthy Subjects:

1. Subjects with any current or previous 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 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 or clinical evidence at screening of significant or unstable cardiac disease etc.
3. Subjects with a history of clinically significant drug allergy
4. Subject with current or history of clinically significant (as determined by the Investigator) skin disease requiring intermittent or chronic treatment
5. Excessive use of alcohol defined as regular consumption of ≥14 units/week for women and ≥21 units/week for men
6. Unwilling to abstain from alcohol use for 48 hours prior to start of dosing through end of study follow up
7. Subjects with Hepatitis A, B, C, D, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection
8. Subjects with renal dysfunction (e.g., estimated creatinine clearance <90 mL/min/1.73 m^2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)

Exclusion Criteria for CHB Subjects:

1. Subjects with any current or previous 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 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 or clinical evidence at screening of significant or unstable cardiac disease etc.
3. Subjects with a history of clinically significant drug allergy
4. Subject with current or history of clinically significant (as determined by the Investigator) skin disease requiring intermittent or chronic treatment
5. Excessive use of alcohol defined as regular consumption of ≥14 units/week for women and ≥21 units/week for men
6. Subjects with Hepatitis A, C, D, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection
7. Subjects with renal dysfunction (e.g., estimated creatinine clearance <90 mL/min/1.73 m^2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula)
8. 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)
9. Subjects must have absence of signs of hepatocellular carcinoma
10. Subjects with history or current liver cirrhosis
11. Subjects positive for anti-HBs antibodies
12. Subjects with liver fibrosis that is classified as Metavir Score ≥F3

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALG-020572; Subcutaneous injections of ALG-020572 in HV or CHB subjects, up to 7 injections over the course of up to 29 days	Drug: ALG-020572; Single or multiple doses of ALG-020572
Placebo Comparator: Placebo; Subcutaneous injections of placebo in HV or CHB subjects, up to 7 injections over the course of up to 29 days	Drug: Placebo; Single or multiple doses of Placebo

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 60 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 120 days for Part 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration [Cmax]	Pharmacokinetic parameters of ALG-020572 in plasma	Predose (0 hours) up to 45 Days (1080 hours)
Area under the concentration time curve [AUC]	Pharmacokinetic parameters of ALG-020572 in plasma	Predose (0 hours) up to 45 Days (1080 hours)
Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of ALG-020572 in plasma	Predose (0 hours) up to 45 Days (1080 hours)
Half-time [t1/2]	Pharmacokinetic parameters of ALG-020572 in plasma	Predose (0 hours) up to 45 Days (1080 hours)
Minimum Plasma Concentration [Cmin]	Pharmacokinetic parameters of ALG-020572 in plasma	Predose (0 hours) up to 45 Days (1080 hours)
Change in HBsAg (reduction) from baseline through Day 120 in Multiple Dose HBV Infected Patients		Screening, Day 1, 2, 4, 8, 11, 15, 22, 29, 36, 45, 60, 90, 120

Collaborators and Investigators

• Sponsor: Aligos Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2021
• Primary Completion (Actual): July 18, 2022
• Study Completion (Actual): July 18, 2022

Study Registration Dates

• First Submitted: August 6, 2021
• First Submitted That Met QC Criteria: August 6, 2021
• First Posted (Actual): August 11, 2021

Study Record Updates

• Last Update Posted (Actual): April 25, 2023
• Last Update Submitted That Met QC Criteria: April 21, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: ALG-020572-401

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No