Efimosfermin alfa for adults with liver 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 trial will test a single dose of efimosfermin alfa in adults with cirrhosis-related hepatic impairment from steatotic liver disease, with and without significant alcohol use, to measure drug levels and safety.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 32 (estimated) |
| Ages | 18 Years to 70 Years |
| Sex | All |
| Sponsor | GlaxoSmithKline Industry-sponsored |
| Locations | 3 sites (Rialto, California and 2 other locations) |
| Trial ID | NCT07358546 on ClinicalTrials.gov |
What this trial studies
This Phase 1 interventional trial gives a single dose of efimosfermin alfa to adults who have chronic, stable hepatic impairment due to steatotic liver disease and classifies participants by Child-Pugh score (B or C). The main goals are to characterize pharmacokinetics and monitor safety and tolerability across different degrees of liver dysfunction and alcohol exposure. Eligible participants are adults 18–70 years with BMI 23–40 kg/m2 and documented cirrhosis; stability of hepatic function is required prior to dosing. Study visits occur at GSK investigational sites in the United States and include blood sampling and clinical safety assessments.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18–70 with BMI 23–40 kg/m2, a documented diagnosis of cirrhosis from steatotic liver disease, and stable chronic hepatic impairment classified as Child-Pugh B or C, with or without significant alcohol use.
Not a fit: Patients with acute or recently worsening liver function, unstable hepatic disease, outside the specified age or BMI ranges, or without steatotic cirrhosis are unlikely to benefit from participating in this study.
Why it matters
Potential benefit: If successful, the results could guide safer dosing and use of efimosfermin alfa in patients with varying degrees of liver impairment.
How similar studies have performed: Pharmacokinetic and safety studies in people with hepatic impairment are a standard step and have been done for many drugs, but published data specifically on efimosfermin alfa in this population are limited.
Eligibility criteria
Show full inclusion / exclusion criteria
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.
Where this trial is running
Rialto, California and 2 other locations
- GSK Investigational Site — Rialto, California, United States (Recruiting)
- GSK Investigational Site — Tampa, Florida, United States (Recruiting)
- GSK Investigational Site — San Antonio, Texas, United States (Recruiting)
Study contacts
- Study coordinator: US GSK Clinical Trials Call Center
- Email: GSKClinicalSupportHD@gsk.com
- Phone: 877-379-3718
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.