A 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
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Brief Summary
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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

Official Title
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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)

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: ALG-010133
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Healthy Subjects: Male and Female between 18 and 55 years old Female subjects must have a negative serum pregnancy test at screening Subjects must be nonsmokers for at least 3 months prior to randomization BMI 18.0 to 32.0 kg/m^2 Subjects must have a 12-lead ECG that meets protocol criteria Inclusion Criteria for CHB Subjects: Male and Female between 18 and 70 years old Female subjects must have a negative serum pregnancy test at screening BMI 18.0 to 35.0 kg/m^2 HBeAg-negative chronic hepatitis B or HBeAg-positive chronic hepatitis B and are currently receiving HBV NA treatment for ≥6 months prior to screening Subjects must have a 12-lead ECG that meets protocol criteria Exclusion Criteria for Healthy Subjects: 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 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. Subjects with a history of clinically significant drug allergy Subject with current or history of clinically significant (as determined by the Investigator) skin disease requiring intermittent or chronic treatment Excessive use of alcohol defined as regular consumption of ≥14 units/week for women and ≥21 units/week for men Unwilling to abstain from alcohol use for 48 hours prior to start of dosing through end of study follow up Subjects with Hepatitis A, B, C, D, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection 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: 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 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. Subjects with a history of clinically significant drug allergy Subject with current or history of clinically significant (as determined by the Investigator) skin disease requiring intermittent or chronic treatment Excessive use of alcohol defined as regular consumption of ≥14 units/week for women and ≥21 units/week for men Subjects with Hepatitis A, C, D, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection 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) 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) Subjects must have absence of signs of hepatocellular carcinoma Subjects with history or current liver cirrhosis Subjects positive for anti-HBs anitbodies Subjects with liver fibrosis that is classified as Metavir Score ≥F3

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALG-010133<br>Subcutaneous injections of ALG-010133 in HV or CHB subjects up to every 7 days for up to 12 weeks | Drug: ALG-010133<br>* Single or multiple doses of ALG-010133<br>|
| Placebo Comparator: Placebo<br>Subcutaneous injections of placebo in HV or CHB subjects up to every 7 days for up to 12 weeks | Drug: Placebo<br>* Single or multiple doses of Placebo<br>|

What is the study measuring?
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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 |