Chronic Hepatitis B Infection
Conditions
Keywords
Chronic Hepatitis B Infection
Brief summary
This is a Phase 1 non-randomized, open-label, single-dose study of pevifoscorvir sodium (also known as ALG-000184) in participants with severe renal impairment (Part 1), in participants with mild or moderate renal impairment (Optional Part 2) and in participants without renal impairment (Parts 1 and 2), matched for age, body weight and, to the extent possible, for sex.
Interventions
Pevifoscorvir Sodium (ALG-000184) Single oral doses of 100 mg pevifoscorvir sodium
Sponsors
Aligos Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a Phase 1 non-randomized, open-label, single-dose study of pevifoscorvir sodium (also known as ALG-000184) in participants with severe renal impairment (Part 1), in participants with mild or moderate renal impairment (Optional Part 2) and in participants without renal impairment (Parts 1 and 2), matched for age, body weight and, to the extent possible, for sex.
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, sex 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 recent 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 |
|---|---|---|
| Area under the concentration time curve [AUC] | Up to 4 days | Plasma PK parameters in each cohort of total ALG-001075 and the metabolite ALG-000302 |
| Maximum plasma concentration [Cmax] | Up to 4 Days | Plasma PK parameters in each cohort of total ALG-001075 and the metabolite ALG-000302 |
| Minimum plasma concentration [Cmin] | Up to 4 Days | Plasma PK parameters in each cohort of total ALG-001075 and the metabolite ALG-000302 |
| C0 [predose] | Up to 4 days | Plasma PK parameters in each cohort of total ALG-001075 and the metabolite ALG-000302 |
| Half-life [t1/2] | Up to 4 Days | Plasma PK parameters in each cohort of total ALG-001075 and the metabolite ALG-000302 |
| Time to maximum plasma concentration [Tmax] | Up to 4 Days | Plasma PK parameters in each cohort of total ALG-001075 and the metabolite ALG-000302 |
| Apparent Clearance (CL/F) | Up to 4 Days | Plasma PK parameters in each cohort of total ALG-001075 and the metabolite ALG-000302 |
| Apparent Volume of Distribution (V/F) | Up to 4 Days | Plasma PK parameters in each cohort of total ALG-001075 and the metabolite ALG-000302 |
| Total Amount of Drug Excreted in Urine (Ae) | Up to 4 Days | Urine PK parameters in each cohort of total ALG-001075 and the metabolite ALG-000302 |
| Renal Clearance (CLr) | Up to 4 Days | Urine PK parameters in each cohort of total ALG-001075 and the metabolite ALG-000302 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] | Up to 15 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 |
Countries
United States
Outcome results
None listed