Clinical trial NCT06568861: A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of ALG-097558 in Subjects with Hepatic Impairment and in Healthy Subjects with Normal Hepatic Function
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: COVID-19
Lead sponsor: Aligos Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2024-08-23
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is non-randomized, open-label, parallel group study. Cohort 1 will enroll moderately hepatically impaired subjects and Cohort 2 will enroll subjects without hepatic impairment.
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 non-randomized, open-label, multiple dose, parallel-group study of ALG-097558 in subjects with moderate hepatic impairment and subjects without hepatic impairment, matched for age, body weight and, to the extent possible, for gender. The primary purpose of this study is to characterize the effect of hepatic impairment on the plasma pharmacokinetics of ALG-097558 following administration of multiple, twice daily (Q12H) oral (PO) doses.


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

Primary outcomes:
measure: Area under the concentration time curve [AUC]
timeFrame: Pre-dose (-0.75 hours) up to Day 8
measure: Time to maximum plasma concentration [Tmax]
timeFrame: Pre-dose (-0.75 hours) up to Day 8
measure: Maximum plasma concentration [Cmax]
timeFrame: Pre-dose (-0.75 hours) up to Day 8
measure: Minimum plasma concentration [Cmin]
timeFrame: Pre-dose (-0.75 hours) up to Day 8
measure: C0 [predose]
timeFrame: Pre-dose (-0.75 hours) up to Day 8
measure: Half-life [t1/2]
timeFrame: Pre-dose (-0.75 hours) up to Day 8
Secondary outcomes:
measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
timeFrame: Up to 20 Days
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
Study officials:
References: