Liver Diseases, Alcoholic
Conditions
Keywords
Efimosfermin alfa, Alcohol-related liver disease, Liver stiffness measurement, Advanced chronic liver disease
Brief summary
This is a dose-ranging study to evaluate safety of efimosfermin alfa and to establish proof-of-concept that efimosfermin alfa therapy provides benefit in participants with ALD.
Interventions
Efimosfermin alfa will be administered.
DRUGPlacebo
Placebo will be administered.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be 18 to 75 years of age inclusive, at the time of Screening. * Capable of giving signed informed consent prior to the performance of any study-specific procedures. * Able and willing to comply with all study assessments and adhere to the protocol schedule of activities. * History of heavy alcohol consumption for greater than 6 months at any time prior to Screening. * A female participant is eligible to participate if they are not pregnant or breastfeeding, and one of the following conditions applies: * Is a Participant of non-childbearing potential (PONCBP) OR * Is a Participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective, with a failure rate of less than (\<)1 percentage (%), 30 days prior to and during the study intervention period and for at least 16 weeks after the last dose of study intervention.
Exclusion criteria
* Other primary causes of liver disease (e.g., viral hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, hemochromatosis, alpha-1-antitryspin deficiency, etc.). Alcohol must be the primary cause of liver disease. * Co-infection with Hepatitis B virus (HBV), Hepatitis C virus (HCV), or Human immunodeficiency virus (HIV) as indicated from the central lab * History of diabetes mellitus (DM), either: * Type 1 DM * Type 2 DM with unstable glycemic control or with major complications. * History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in situ cervical cancer), treated or untreated, within the 3 years prior to Screening 1, regardless of any evidence of local recurrence or metastasis. * Current, or history of known hepatocellular carcinoma (HCC). * Any major surgery within 3 months prior to Screening 1 or planned during the study * Any surgical or medical condition that might jeopardize the individual's safety or compliance with study procedures in the opinion of the investigator. * All organ transplant recipients, except for history of corneal transplants, or current listing or active consideration for liver transplant during the Screening period. * Poorly controlled hypertension. * Evidence of Wernicke-Korsakoff syndrome or alcohol-related dementia. * Prior use of a Fibroblast growth factor 21 (FGF21) analogue, including efimosfermin, within the 6 months prior to Screening 1. * Individuals with a history of resmetirom use within 3 months prior to Day 1 are to be excluded. * Concomitant use of investigational drugs for Metabolic dysfunction-associated steatohepatitis (MASH) or ALD. * Current or planned participation in any clinical trial of investigational therapies or medical devices. * Exceeding pre-defined laboratory parameters for Triglycerides, Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), International normalised ratio (INR), Albumin, Urine albumin-creatinine ratio (uACR) or Glycosylated Hemoglobin (HbA1c). * History of drug abuse within the 12 months prior to Day 1 or evidence of such abuse as indicated by laboratory assays conducted at Screening. * History of hypersensitivity (such as anaphylaxis or hepatotoxicity) to study intervention and/or its excipients, drugs of similar biological class, FGF21 protein analogs, Fc-fusion proteins, or other protein-based therapeutics. * Overt hepatic encephalopathy (West Haven grade \>=2).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in vibration-controlled transient elastography-liver stiffness measurement (VCTE-LSM) | Baseline (Day 1) and up to Week 60 | VCTE-LSM is a non-invasive test that uses vibration-controlled transient elastography to measure the stiffness of the liver in kilopascals (kPa) |
| Change from Baseline in model for end-stage liver disease (MELD) score | Baseline (Day 1) and up to Week 60 | MELD is a scoring system for assessing the severity of chronic liver disease. MELD scores range between 6 and 40, with 40 being the most severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in serum aspartate aminotransferase (AST) (International units per liter) | Baseline (Day 1) and up to Week 60 | This is a measurement of the AST enzyme in the blood. |
| Change from Baseline in a blood test that helps predict the risk of disease progression in liver disease | Baseline (Day 1) and up to Week 52 | — |
| Trough Concentration at steady state (Ctrough,ss) following administration of efimosfermin alfa | Up to Week 56 | — |
| Area Under the concentration-time Curve from Time 0 (pre-dose) to the last quantifiable concentration (AUC[0-t]) of efimosfermin alfa in the subset of participants with optional intensive pharmacokinetics (PK) sampling | Up to Week 4 | — |
| Maximum observed drug concentration (Cmax) of efimosfermin alfa in the subset of participants with optional intensive PK sampling | Up to Week 4 | — |
| Number of Participants with Anti-drug antibodies (ADA) against efimosfermin alfa | Up to Week 56 | — |
| Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity | Up to Week 60 | — |
| Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity | Up to Week 60 | — |
| Number of participants with Grade 3 and Grade 4 laboratory abnormalities | Up to Week 60 | — |
| Number of participants with clinically significant changes in Vital signs | Up to Week 60 | — |
| Number of participants with clinically significant changes in 12-lead electrocardiogram (ECG) findings | Up to Week 60 | — |
Countries
United States
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Outcome results
None listed