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

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)

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

Study Overview

• Status: Terminated
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: ALG-125755; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria
    • MBAL Sveta Sofia EOOD, Dept of Internal Medicine with Gastroenterology Section
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • PMSI Republican Clinical Hospital "t. Mosneaga", ARENSIA Exploratory Medicine Phase 1 Unit
• New Zealand
  • Auckland, New Zealand
    • New Zealand Clinical Research
• Romania
  • Bucharest, Romania
    • National Institute for Infection Diseases, ARENSIA Exploratory Medicine S.R.L.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 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 Subjects:

1. Male or female between 18 and 55 years of age, extremes included.
2. 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):

1. Subjects must be 18 to 70 years of age, inclusive of extremes.
2. Subjects may have a BMI of 18.0 to 35.0 kg/m2, extremes included.
3. 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:

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 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 (Part 1):

1. Unwilling to abstain from alcohol use for 48 hours prior to start of study through end of study follow up.
2. 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):

1. Subjects who are positive for anti-HBs antibodies.
2. 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).
3. History or current evidence of cirrhosis.
4. Subjects with liver fibrosis that is classified as Metavir Score ≥F3 liver disease
5. Subjects must have absence of signs of hepatocellular carcinoma

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-125755; 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; single or multiple doses of ALG-125755
Placebo Comparator: Placebo; Subcutaneous injections of placebo in HV or CHB subjects, up to 6 injections over the course of up to 72 weeks	Drug: Placebo; single or multiple doses of placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Aligos Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2022
• Primary Completion (Actual): June 15, 2023
• Study Completion (Actual): June 15, 2023

Study Registration Dates

• First Submitted: September 26, 2022
• First Submitted That Met QC Criteria: September 28, 2022
• First Posted (Actual): September 30, 2022

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Chronic Disease; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: ALG-125755-501

Drug and device information, study documents

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