A Study of Efimosfermin Alfa in Adults With Hepatic Impairment

Официальное название

A Phase 1, Open-label, Single-dose Study to Evaluate the Pharmacokinetics and Safety of Efimosfermin Alfa in Adults With Varying Degrees of Hepatic Impairment Due to Steatotic Liver Disease

Обзор

This study is designed to study the pharmacokinetic (PK) and safety profiles of a single dose of efimosfermin alfa in participants with varying degrees of Hepatic Impairment (HI) (assessed by Child-Pugh score) due to steatotic liver disease, with and without significant alcohol consumption.

Вмешательства

• Препарат Efimosfermin alfa
  Efimosfermin alfa to be administrated subcutaneously

Первичные конечные точки

• Area under the serum drug concentration versus time curve from time zero to infinity (AUC[0-inf]) of efimosfermin alfa [Срок оценки: Up to 90 Days]
• Maximum observed serum drug concentration (Cmax) of efimosfermin alfa [Срок оценки: Up to 90 Days]

Вторичные конечные точки (10)

• Number of participants with Adverse Events (AEs), treatment related AEs and serious adverse events (SAEs) [Срок оценки: Up to 90 Days]
• Number of participants with clinically significant changes in hematology, chemistry, and urinalysis parameters [Срок оценки: Up to 90 Days]
• Number of participants with clinically significant changes in Vital signs and 12-lead electrocardiogram (ECG) findings [Срок оценки: Up to 90 Days]
• Area under the serum drug concentration versus time curve from time zero to the time of the last quantifiable concentration (AUC[0-t]) of efimosfermin alfa [Срок оценки: Up to 90 Days]
• Time to maximum observed serum drug concentration (Tmax) of efimosfermin alfa [Срок оценки: Up to 90 Days]
• Apparent terminal phase half-life (t1/2) of efimosfermin alfa [Срок оценки: Up to 90 Days]
• Time prior to the first measurable (non-zero) serum concentration (Tlag) of efimosfermin alfa [Срок оценки: Up to 90 Days]
• Apparent clearance (CL/F) of efimosfermin alfa [Срок оценки: Up to 90 days]
• Apparent terminal phase volume of distribution (Vz/F) of efimosfermin alfa [Срок оценки: Up to 90 days]
• Terminal elimination rate constant (Lambda z) of efimosfermin alfa [Срок оценки: Up to 90 days]

Критерии участия

Критерии включения

• Between 18 years and 70 years of age inclusive
• Body Mass Index (BMI) within the range 23-40 kilogram per square meter (kg/m\^2)
• Male or female participants
• Participant has liver cirrhosis with a grade of hepatic impairment that can be classified as a discrete Child-Pugh class. Participants must:

• Have a clinical diagnosis of liver cirrhosis in the participant's medical history corroborated by previous liver biopsy, medical imaging or compatible biochemical profile, and
• Be classed during Screening as one of the following Child-Pugh classes:

• Child-Pugh B: Score 7-9 or
• Child-Pugh C: Score 10-15
• Chronic (greater than \[>\] 6 months) HI which is currently stable (no acute episodes of illness within the previous 1 month prior to Screening (Visit 1) due to deterioration in hepatic function). Participants must also remain stable throughout the Screening period. Assessment of the stability of the participant's hepatic function will be determined by the investigator.

Критерии исключения

• History of extrahepatic disorders possibly related to etiology of cirrhosis.
• History of cryoglobulinemia.
• Participants with Grade 3 ascites or refractory ascites.
• Participants with refractory encephalopathy or significant central nervous system disease
• History of gastric or esophageal variceal bleeding within the past 6 months and for which varices have not been adequately treated with medication and/or surgical procedures.
• Other primary causes of liver disease. Steatotic liver disease must be the primary cause of liver disease.
• Clinically significant abnormalities affecting physical health in medical history, or on physical examination, that could interfere with or for which treatment could interfere with the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the participant in this study.
• Current, or history of known hepatocellular carcinoma (HCC).
• Participants with transjugular intrahepatic portosystemic shunt (TIPS) placement.
• Presence of hepatopulmonary or hepatorenal syndrome.
• Presence of primarily cholestatic liver diseases.
• Evidence of symptomatic or complicated cholecystitis.
• History of pancreatic injury, pancreatitis, or other pancreatic disease.
• History of liver transplantation, or active on the liver transplant waiting list.
• Participants with signs of active infection
• History of adrenal gland disease or using treatment that affects the hypothalamic-pituitary-adrenal axis.
• History of significant bone disease such as osteoporosis
• Psychosocial features that, in the opinion of the investigator, increase the likelihood of loss to follow-up.
• History or presence of drug abuse.
• Use of other investigational drugs at the time of screening, or within 5 half-lives or 30 days prior to study intervention, whichever was longer; or longer if required by local regulations
• Have previously taken efimosfermin alfa
• Participants with Alanine Aminotransferase (ALT) value >3 times (x) upper limit of normal (ULN)
• Participants with Aspartate aminotransferase (AST) value >=300 Units/Liter.
• Participants with estimated glomerular filtration rate (eGFR) (Chronic Kidney Disease Epidemiology \[CKD-Epi\] 2021) <45 milliliter/minute/1.73 square meter (mL/min/1.73m\^2).
• Average of triplicate QT interval corrected for heart rate using Fridericia formula (QTcF) >480 milliseconds (msec) (for male and female participants) at Screening
• For participants in the MASH with alcohol category, significant risk of withdrawal symptoms.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• GSK Investigational Site — Rialto
• GSK Investigational Site — Tampa
• GSK Investigational Site — San Antonio

Идентификаторы

NCT: NCT07358546 · 306836

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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