A Study of Efimosfermin Alfa in Adults With Hepatic Impairment

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

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.

Study Overview

• Status: Recruiting
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: Efimosfermin alfa

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Study Locations

• United States
  • California
    • Rialto, California, United States, 92377
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Zeid Kayali
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
  • Florida
    • Tampa, Florida, United States, 33603
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Jesus Navarro
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
  • Texas
    • San Antonio, Texas, United States, 78215
      • Recruiting
      • GSK Investigational Site
      • Principal Investigator: Eric Lawitz
      • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
      • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 (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.

Exclusion Criteria:

• 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 corrected QT interval, (QTc) >480 milliseconds (msec) (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efimosfermin alfa in participants with moderate hepatic impairment due to MASH without alcohol; All participants will receive efimosfermin alfa. Participants will have moderate hepatic impairment (Child-Pugh B) due to Metabolic Dysfunction-Associated Steatohepatitis (MASH) with typical alcohol consumption threshold in the 3 months prior to Screening of less than (<) 5 standard drinks on any day and <15 standard drinks per week for men; or <4 standard drinks on any day and <8 standard drinks per week for women.	Drug: Efimosfermin alfa; Efimosfermin alfa to be administrated subcutaneously
Experimental: Efimosfermin alfa in participants with moderate hepatic impairment due to MASH with alcohol; All participants will receive efimosfermin alfa. Participants will have moderate hepatic impairment (Child-Pugh B) due to MASH with typical alcohol consumption threshold in the 3 months prior to Screening of greater than or equal to (>=) 5 standard drinks per day or >=15 standard drinks per week for men; or >= 4 standard drinks per day or >=8 or more drinks per week for women.	Drug: Efimosfermin alfa; Efimosfermin alfa to be administrated subcutaneously
Experimental: Efimosfermin alfa in severe hepatic impairment participants due to MASH regardless of alcohol use; All participants will receive efimosfermin alfa. Participants will have severe hepatic impairment (Child-Pugh C) due to MASH with any typical daily alcohol consumption.	Drug: Efimosfermin alfa; Efimosfermin alfa to be administrated subcutaneously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the serum drug concentration versus time curve from time zero to infinity (AUC[0-inf]) of efimosfermin alfa	Up to 90 Days
Maximum observed serum drug concentration (Cmax) of efimosfermin alfa	Up to 90 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Apparent clearance (CL/F) of efimosfermin alfa	Up to 90 days
Number of participants with Adverse Events (AEs), treatment related AEs and serious adverse events (SAEs)	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	Up to 90 Days
Time to maximum observed serum drug concentration (Tmax) of efimosfermin alfa	Up to 90 Days
Apparent terminal phase half-life (t1/2) of efimosfermin alfa	Up to 90 Days
Time prior to the first measurable (non-zero) serum concentration (Tlag) of efimosfermin alfa	Up to 90 Days
Apparent terminal phase volume of distribution (Vz/F) of efimosfermin alfa	Up to 90 days
Terminal elimination rate constant (Lambda z) of efimosfermin alfa	Up to 90 days
Number of participants with clinically significant changes in hematology, chemistry, and urinalysis parameters	Up to 90 Days
Number of participants with clinically significant changes in Vital signs and 12-lead electrocardiogram (ECG) findings	Up to 90 Days

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): March 13, 2026
• Primary Completion (Estimated): October 13, 2027
• Study Completion (Estimated): October 13, 2027

Study Registration Dates

• First Submitted: January 14, 2026
• First Submitted That Met QC Criteria: January 14, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Alcohol; Hepatic Impairment; Metabolic Dysfunction-Associated Steatohepatitis; Steatotic liver disease; efimosfermin alfa
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 306836

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://d3l8i7lo48obsd.cloudfront.net/gsk-patient-level-data-sharing-july2025-1-Bgwa1UthxvluYbWYTThw.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No