A Study to Evaluate the Pharmacokinetics, Safety and Tolerability of ALG-097558 in Subjects With Renal Impairment and in Healthy Subjects With Normal Renal Function

Aligos Therapeutics

Status and phase: Completed; Phase 1

Conditions: COVID 19

Treatments: Drug: ALG-097558

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT06698549

ALG-097558-703 / DMID 24-0022

Details and patient eligibility

About

This is a Phase 1 non-randomized, open-label, multiple dose, parallel-group study of ALG-097558 in subjects with severe renal impairment and subjects without renal 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 renal impairment on the plasma pharmacokinetics of ALG-097558 following administration of multiple, twice daily (Q12H) oral (PO) doses.

Enrollment: 12 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for All Subjects:

1. Male and Female between 18 and 75 years old
2. Body Mass Index (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

Inclusion Criteria for Subjects with Normal Renal Function:

1. Good general health as defined by no clinically relevant abnormalities identified by Medical History and a vital signs, clinical laboratory 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 renal function (estimated Glomerular Filtration Rate [eGFR] ≥90 mL/min) with no known or suspected renal impairment

Inclusion Criteria for Subjects with Impaired Renal Function:

1. Subject satisfies the eGFR criteria for renal impairment classification within 28 days of study drug administration
2. Any form of renal impairment except acute nephritic syndrome (subjects with history of previous nephritic syndrome but in remission can be included).
3. Stable concomitant medications for the management of an individual subject's medical history for at least 28 days prior to screening
4. 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 and 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 (subjects with normal renal function) or unstable (subjects with renal impairment) 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
8. Subjects with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) values >2x upper limit of normal (ULN)
9. Subjects with bilirubin (total, direct) >1.5x ULN (unless Gilbert's is suspected)
10. Positive pregnancy test; females must not be pregnant at enrollment

Exclusion Criteria for Subjects with Normal Renal Function:

1. Hemoglobin <10 g/dL

Exclusion Criteria for Subjects with Impaired Renal Function:

1. Participants requiring hemodialysis and/or peritoneal dialysis
2. Hemoglobin <9 g/dL

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

12 participants in 4 patient groups

Subjects with Severe Renal Impairment

Experimental group

Description:

Subjects with severe renal impairment will receive oral doses of 300 mg ALG-097558 twice daily (every 12 hours \[Q12H\]) for 6 days for 11 total doses.

Treatment:

Drug: ALG-097558

Subjects with Normal Renal Function

Experimental group

Description:

Subjects with normal renal function will receive oral doses of 300 mg ALG-097558 twice daily (every 12 hours \[Q12H\]) for 6 days for 11 total doses.

Treatment:

Drug: ALG-097558

Subjects with Mild Renal Impairment (Optional)

Experimental group

Description:

Subjects with mild renal impairment will receive oral doses of 300 mg ALG-097558 twice daily (every 12 hours \[Q12H\]) for 6 days for 11 total doses.

Treatment:

Drug: ALG-097558

Subjects with Moderate Renal Impairment (Optional)

Experimental group

Description:

Subjects with moderate renal impairment will receive oral doses of 300 mg ALG-097558 twice daily (every 12 hours \[Q12H\]) for 6 days for 11 total doses.

Treatment:

Drug: ALG-097558