Chronic Hepatitis B Infections
Conditions
Keywords
Chronic Hepatitis B Infections
Brief summary
This Phase 1 non-randomized, open-label, single-dose hepatic impairment study consists of 2 cohorts, conducted in 16 subjects, 8 subjects with moderate hepatic impairment (Cohort 1) and 8 subjects without hepatic impairment (Cohort 2), matched for age, body weight and, to the extent possible, for sex. The effect of hepatic impairment on the plasma pharmacokinetics of ALG-001075 will be assessed in subjects who have received single oral doses of pevifoscorvir sodium (ALG-000184).
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 Phase 1 non-randomized, open-label, single-dose hepatic impairment study consists of 2 cohorts, conducted in 16 subjects, 8 subjects with moderate hepatic impairment (Cohort 1) and 8 subjects without hepatic impairment (Cohort 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
No
Inclusion criteria
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 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. Subjects provided they met stable treatment criteria. Subjects with HIV infection may be eligible for moderate impairment cohort provided they met stable treatment criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the concentration time curve [AUC] | Up to 4 days | PK parameters of total ALG-001075 and the major metabolite ALG-000302 in plasma |
| Time to maximum plasma concentration [Tmax] | Update to 4 Days | PK parameters of total ALG-001075 and the major metabolite ALG-000302 in plasma |
| Maximum plasma concentration [Cmax] | Update to 4 days | PK parameters of total ALG-001075 and the major metabolite ALG-000302 in plasma |
| Minimum plasma concentration [Cmin] | Up to 4 days | PK parameters of total ALG-001075 and the major metabolite ALG-000302 in plasma |
| C0 (predose) | Up to 4 days | PK parameters of total ALG-001075 and the major metabolite ALG-000302 in plasma |
| Half-life [t1/2] | Up to 4 Days | PK parameters of total ALG-001075 and the major metabolite ALG-000302 in plasma |
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 adverse events as assessed by DAIDS v2.1 |
Countries
United States
Outcome results
None listed