A Study to Investigate the Safety and Efficacy of Efimosfermin Alfa Compared With Placebo in Adult Participants With Alcohol-related Liver Disease (ALD)

A Dose-finding, Double-blind, Randomized, Placebo-controlled Phase 2 Study to Evaluate the Efficacy and Safety of Treatment With Efimosfermin Alfa in Adult Participants With Alcohol-related Liver Disease (ALD)

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.

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).