A Study of Efimosfermin Alfa in Adults With Hepatic Impairment

GlaxoSmithKline (GSK)

Status and phase: Begins enrollment this month; Phase 1

Conditions: Non-alcoholic Fatty Liver Disease

Treatments: Drug: Efimosfermin alfa

Study type: Interventional

Funder types: Industry

Identifiers

NCT07358546

306836

Details and patient eligibility

About

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.

Enrollment: 32 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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 (>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.

Exclusion criteria

• History of extrahepatic disorders possibly related to etiology of cirrhosis.
• History of cryoglobulinemia.
• Participants with Grade 3
• 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
• 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 of
• History of pancreatic injury, pancreatitis, or other pancreatic disease.
• History of liver transplantation.
• 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-
• 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 x upper limit of normal (ULN)
• Average of triplicate corrected QT interval, (QTc) >480 msec in (for male and female participants)participants with bundle branch block at Day -1 (Visit 2) (a mean of triplicate measurements should be used to confirm that the participant meets exclusion criterion).
• For participants in the MASH with alcohol category, significant risk of withdrawal symptoms:

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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32 participants in 3 patient groups

Efimosfermin alfa in participants with moderate hepatic impairment due to MASH without alcohol

Experimental group

Description:

All participants will receive efimosfermin alfa. Participants will have moderate hepatic impairment (Child-Pugh B) due to Metabolic Dysfunction-Associated Steatohepatitis (MASH) with typical average daily alcohol consumption threshold of less than or equal to (\<=) 30 gram ethanol or \<=5 standard drinks (men), or \<=16 gram ethanol or \<=4 standard drinks (women) per day for 3 months prior to Screening.

Treatment:

Drug: Efimosfermin alfa

Efimosfermin alfa in participants with moderate hepatic impairment due to MASH with alcohol

Experimental group

Description:

All participants will receive efimosfermin alfa. Participants will have moderate hepatic impairment (Child-Pugh B) due to MASH with typical average daily alcohol consumption threshold of greater than (\>) 30 gram ethanol or \>5 standard drinks (men) or \>16 gram ethanol or \>4 standard drinks (women) per day for 3 months prior to Screening.

Treatment:

Drug: Efimosfermin alfa

Efimosfermin alfa in participants with severe hepatic impairment due to MASH despite of alcohol use

Experimental group

Description:

All participants will receive efimosfermin alfa. Participants will have severe hepatic impairment (Child-Pugh C) due to MASH with any typical daily alcohol consumption.

Treatment:

Drug: Efimosfermin alfa