COVID 19
Conditions
Brief summary
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.
Interventions
DRUGALG-097558
Multiple doses of ALG-097558 300 mg (3 x 100 mg tablets)
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Aligos Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study is non-randomized, open-label, parallel group study. In Part 1, Cohort 1 will enroll severely renally impaired subjects and Cohort 2 will enroll subjects without renal impairment. In Part 2, if triggered, Cohort 3 will enroll mildly renally impaired subjects and Cohort 4 moderately renally impaired subjects. Cohort 5 will enroll subjects without renal impairment.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Renal Clearance (CLr) | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in urine |
| Minimum plasma concentration [Cmin] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma |
| Area under the concentration time curve [AUC] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma |
| Maximum plasma concentration [Cmax] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma |
| C0 [predose] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma |
| Half-life [t1/2] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma |
| Time to maximum plasma concentration [Tmax] | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma |
| Apparent Clearance (CL/F) | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma |
| Apparent Volume of Distribution (V/F) | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in plasma |
| Total Amount of Drug Excreted in Urine (Ae) | Pre-dose (-0.75 hours) up to Day 8 | Pharmacokinetic parameters of ALG-097558 and metabolite ALG-097730 in urine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Up to 20 Days | The number and severity of treatment emergent events in subjects with renal impairment and subjects with normal renal function as assessed by DAIDS v2.1 (July 2017) |
Countries
United States
Outcome results
None listed