Single-Dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of Pevifoscorvir Sodium (ALG-000184) in Subjects With Moderate Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function

Official title

A Phase 1 Non-Randomized, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics, Safety- and Tolerability of Pevifoscorvir Sodium (ALG-000184) in Subjects With Moderate Hepatic Impairment and in Healthy Subjects With Normal Hepatic Function

Overview

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

• Drug Pevifoscorvir Sodium (ALG-000184)
  Pevifoscorvir Sodium (ALG-000184) Single oral doses of 100 mg pevifoscorvir sodium

Primary outcome measures

• Area under the concentration time curve [AUC] [Time frame: Up to 4 days]
• Time to maximum plasma concentration [Tmax] [Time frame: Update to 4 Days]
• Maximum plasma concentration [Cmax] [Time frame: Update to 4 days]
• Minimum plasma concentration [Cmin] [Time frame: Up to 4 days]
• C0 (predose) [Time frame: Up to 4 days]
• Half-life [t1/2] [Time frame: Up to 4 Days]

Secondary outcome measures (1)

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] [Time frame: Up to 15 days]

Eligibility criteria

Inclusion criteria

• Male and Female between 18 and 75 years old
• BMI 17.5 to 40.0 kg/m\^2 and a total body weight >50 kg (110 lb)
• 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
• Female subjects must have a negative serum pregnancy test at screening

Inclusion Criteria for Subjects with Normal Hepatic Function:

• Good general health as defined by no clinically relevant abnormalities identified by Medical History and a vital signs and 12-lead electrocardiogram (ECG) assessment
• Subjects must fit the demographic-matching criteria including body weight, age, and to the extent possible, gender
• Normal hepatic function with no known or suspected hepatic impairment

Inclusion Criteria for Subjects with Impaired Hepatic Function:

• 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
• 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)
• Stable hepatic impairment for at least 3 months prior to screening or second screening visit to demonstrate stability
• 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:

• 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
• 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.
• Subjects with a history of clinically significant drug allergy
• Subjects with a recent (within 1 year of randomization) history or current evidence of drug abuse or recreational drug use
• Excessive use of alcohol defined as regular consumption of ≥14 units/ week for women and ≥21 units/week for men
• Unwilling to abstain from alcohol use for 48 hours prior to start of the study through end of study follow up
• 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.

Exclusion Criteria for Subjects with Normal Hepatic Function:

• 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
• Bilirubin (total, direct) >1.2× upper limit of normal (ULN) (unless Gilbert's is suspected)
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level > 1.2×ULN
• Grade ≥1 Hemoglobin

Exclusion Criteria for Subjects with Impaired Hepatic Function:

• Subjects with advanced ascites (Grade 3)
• Subjects with refractory encephalopathy as judged by the investigator.
• Subjects with esophageal variceal bleeding within the past 6 months prior to screening.
• Subjects with Transjugular Intrahepatic Portosystemic Shunt (TIPS) placement.
• 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
• ALT or AST level ≥5×ULN
• Serum sodium ≤125 mmol/L
• Platelets <50×10\^9/L
• Grade ≥2 Hemoglobin

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Orlando Clinical Research Center — Orlando

Identifiers

NCT: NCT07342868 · ALG-000184-207

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗