A Study of ALG-125755 to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single Doses in Healthy Volunteers, and Single and Multiple Doses in CHB Subjects

Study Overview
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Brief Summary
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A randomized study of ALG-125755 to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics after single doses in healthy volunteers, and single and multiple doses in CHB subjects

Official Title
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A Phase 1/1b, Double-Blind, Randomized, Placebo-Controlled, First-in-Human Study of Subcutaneously Administered ALG-125755 to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics After Single Ascending Doses in Healthy Volunteers (Part 1) and Subjects With Chronic Hepatitis B (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-125755
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for All Subjects: Female subjects must have a negative serum pregnancy test at screening Subjects must have a 12-lead electrocardiogram (ECG) that meets the protocol criteria Inclusion Criteria for Healthy Subjects: Male or female between 18 and 55 years of age, extremes included. Subjects must have a body mass index (BMI) of 18.0 to 32.0 kg/m2, extremes included. Inclusion Criteria for CHB Subjects (Parts 2 and 3): Subjects must be 18 to 70 years of age, inclusive of extremes. Subjects may have a BMI of 18.0 to 35.0 kg/m2, extremes included. 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 Exclusion Criteria for All 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 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 Exclusion Criteria for Healthy Volunteers (Part 1): Unwilling to abstain from alcohol use for 48 hours prior to start of study through end of study follow up. Subjects with renal dysfunction [e.g., estimated creatinine clearance <90 mL/min/1.73 m2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula] Exclusion criteria for CHB subjects (Parts 2 and 3): Subjects who are positive for anti-HBs antibodies. 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 must have absence of signs of hepatocellular carcinoma

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-125755<br>Subcutaneous injections of ALG-125755 in HV or CHB subjects, up to 6 injections over the course of up to 72 weeks | Drug: ALG-125755<br>* single or multiple doses of ALG-125755<br>|
| Placebo Comparator: Placebo<br>Subcutaneous injections of placebo in HV or CHB subjects, up to 6 injections over the course of up to 72 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 and severity of treatment emergent adverse events as assessed by DAIDS v2.1 of various doses of ALG-125755 in HV subjects and CHB subjects |  | Up to 32 days for Part 1 | 
| Incidence and severity of treatment emergent adverse events as assessed by DAIDS v2.1 |  | Up to 52 days for Part 2 | 
| Incidence and severity of treatment emergent adverse events as assessed by DAIDS v2.1 |  | Up to 616 days for Part 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration (Cmax) | Pharmacokinetic parameters of ALG-125755 in plasma | Predose (0 hours) up to 616 days | 
| Area under the concentration time curve [AUC] | Pharmacokinetic parameters of ALG-125755 in plasma | Predose (0 hours) up to 616 days | 
| Time to maximum plasma concentration [Tmax] | Pharmacokinetic parameters of ALG-125755 in plasma | Predose (0 hours) up to 616 days | 
| Antiviral activity of ALG-125755 as measured by quantitative changes in serum | Pharmacokinetic parameters of ALG-125755 in plasma | Predose (0 hours) up to 616 days | 
| Minimum plasma concentration (Cmin) | Pharmacokinetic parameters of ALG-125755 in plasma | Predose (0 hours) up to 616 days | 
| Change in HBsAg from baseline through up to 112 days from last dose in multiple dose HBV infected subjects |  | screening to up to 112 days |