A Study of ALG-010133 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 Subcutaneously Administered ALG-010133 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-010133 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: ALG-010133; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 103
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • 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
• Korea, Republic of
  • Busan, Korea, Republic of
    • Pusan National University Hospital
  • Seoul, Korea, Republic of
    • Seoul National University Hospital
  • Seoul, Korea, Republic of
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Severance Hospital, Yonsei University Health System
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • PMSI Republican Clinical Hospital "T. Mosneaga", ARENSIA Exploratory Medicine Phase I Unit
• New Zealand
  • Auckland, New Zealand
    • ACS
• United Kingdom
  • London, United Kingdom
    • King's College Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

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. Subjects must be nonsmokers for at least 3 months prior to randomization
4. BMI 18.0 to 32.0 kg/m^2
5. Subjects must have a 12-lead ECG that meets protocol criteria

Inclusion Criteria for CHB Subjects:

1. Male and Female between 18 and 70 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. HBeAg-negative chronic hepatitis B or HBeAg-positive chronic hepatitis B and are currently receiving HBV NA treatment for ≥6 months prior to screening
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 anitbodies
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-010133; Subcutaneous injections of ALG-010133 in HV or CHB subjects up to every 7 days for up to 12 weeks	Drug: ALG-010133; Single or multiple doses of ALG-010133
Placebo Comparator: Placebo; Subcutaneous injections of placebo in HV or CHB subjects up to every 7 days for up to 12 weeks	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 15 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 29 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 162 days for Part 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Plasma Concentration [Cmax]	Pharmacokinetic parameters of ALG-010133 in plasma	Predose (0 hours) up to 162 Days (3864 hours)
Area under the concentration time curve [AUC]	Pharmacokinetic parameters of ALG-010133 in plasma	Predose (0 hours) up to 162 Days (3864 hours)
Time to maximum plasma concentration [Tmax]	Pharmacokinetic parameters of ALG-010133 in plasma	Predose (0 hours) up to 162 Days (3864 hours)
Half-time [t1/2]	Pharmacokinetic parameters of ALG-010133 in plasma	Predose (0 hours) up to 162 Days (3864 hours)
Minimum Plasma Concentration [Cmin]	Pharmacokinetic parameters of ALG-010133 in plasma	Predose (0 hours) up to 162 Days (3864 hours)
Change in HBsAg (reduction) from baseline through Day 78 in Multiple Dose HBV Infected Patients		Screening, Day -1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78

Collaborators and Investigators

• Sponsor: Aligos Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2020
• Primary Completion (Actual): March 8, 2022
• Study Completion (Actual): March 8, 2022

Study Registration Dates

• First Submitted: July 9, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: March 1, 2022

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-010133-101

Drug and device information, study documents

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