Evaluating the effects of ALG-097558 in patients with liver impairment and healthy individuals

A Phase 1 Non-Randomized, Open-Label, Multiple Dose Study to Evaluate the Pharmacokinetics, Safety and Tolerability of ALG-097558 in Subjects with Moderate Hepatic Impairment and in Healthy Subjects with Normal Hepatic Function

This study is testing how the drug ALG-097558 works in people with liver problems compared to healthy individuals to see if it's safe and how the body handles it.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Aligos Therapeutics (industry)
• Locations: 2 sites (Miami, Florida and 1 other locations)
• Trial ID: NCT06568861 on ClinicalTrials.gov

What this trial studies

This Phase 1 study investigates the pharmacokinetics, safety, and tolerability of the drug ALG-097558 in individuals with moderate hepatic impairment compared to healthy subjects with normal liver function. The study is non-randomized and open-label, involving multiple doses administered twice daily. Participants will be matched based on age, body weight, and gender to ensure comparability between the two groups. The primary goal is to understand how liver impairment affects the drug's behavior in the body.

Who should consider this trial

Good fit: Ideal candidates include males and females aged 18 to 75 with either moderate hepatic impairment or normal hepatic function.

Not a fit: Patients with severe hepatic impairment or those outside the specified age and health criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide critical insights into the safe use of ALG-097558 in patients with liver impairment, potentially improving treatment options for COVID-19.

How similar studies have performed: While this study focuses on a specific drug and population, similar pharmacokinetic studies have shown success in understanding drug behavior in patients with hepatic impairment.

Eligibility criteria

Inclusion Criteria for All Subjects:

1. Male and Female between 18 and 75 years old
2. BMI 17.5 to 40.0 kg/m\^2 and a total body weight \>50 kg (110 lb) 3 .Female subjects must either be not of childbearing potential or if they are a woman of childbearing potential, they are only eligible if they and any non-sterile, male sexual partners agree to use highly effective contraceptive therapy

4. Female subjects must have a negative serum pregnancy test at screening

Inclusion Criteria for Subjects with Normal Hepatic Function:

1. Good general health as defined by no clinically relevant abnormalities identified by Medical History and a vital signs and 12-lead electrocardiogram (ECG) assessment
2. Subjects must fit the demographic-matching criteria including body weight, age, and to the extent possible, gender
3. Normal hepatic function with no known or suspected hepatic impairment

Inclusion Criteria for Subjects with Impaired Hepatic Function:

1. Subject satisfies the criteria for Class B of the Child-Pugh classification (Child Pugh Scores 7-9 points) within 28 days of study drug administration
2. A diagnosis of hepatic dysfunction due to hepatocellular disease (and not secondary to any acute ongoing hepatocellular process) documented by medical history, physical examination, liver biopsy, hepatic ultrasound, Fibroscan, computerized tomography scan, or magnetic resonance imaging (MRI)
3. Stable hepatic impairment for at least 3 months prior to screening or second screening visit to demonstrate stability
4. Stable concomitant medications for the management of an individual subject's medical history for at least 28 days prior to screening
5. Subjects must have a 12-lead ECG and vital signs assessment that meet the protocol criteria

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. Subjects with a recent (within 1 year of randomization) history or current evidence of drug abuse or recreational drug use
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 the study through end of study follow up
7. Subjects with Hepatitis A, B, C, E or HIV-1/HIV-2 infection or acute infections such as SARS- CoV-2 infection. Subejcts with Hepatitis B infection may be eligible for moderate impairment cohort provided provided they met stable treatment criteria. Subjects with HIV infection may be eligible for moderate impairment cohort provided they met stable treatment criteria.

Exclusion Criteria for Subjects with Normal Hepatic Function:

1. Estimated creatinine clearance \<60 mL/min/1.73 m2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula\] - Unless otherwise instructed by the Study Review Committee (SRC), CKD-EPI should not be corrected for subjects of African ancestry
2. Bilirubin (total, direct) \>1.2× upper limit of normal (ULN) (unless Gilbert's is suspected)
3. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level \> 1.2×ULN
4. Grade ≥1 Hemoglobin

Exclusion Criteria for Subjects with Impaired Hepatic Function:

1. Subjects with advanced ascites (Grade 3)
2. Subjects with refractory encephalopathy as judged by the investigator.
3. Subjects with esophageal variceal bleeding within the past 6 months prior to screening.
4. Subjects with Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement.
5. Estimated creatinine clearance \<60 mL/min/1.73 m2 at screening, calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula\] - Unless otherwise instructed by the SRC, CKD-EPI should not be corrected for subjects of African ancestry
6. ALT or AST level ≥5×ULN
7. Serum sodium ≤125 mmol/L
8. Platelets \<50×10\^9/L
9. Grade ≥2 Hemoglobin

Where this trial is running

Miami, Florida and 1 other locations

• University of Miami — Miami, Florida, United States (RECRUITING)
• Orlando Clinical Research Center — Orlando, Florida, United States (RECRUITING)

Study contacts

• Study coordinator: Jen Rito

Conditions: COVID-19