Dysautonomia International

A Pivotal Clinical Study to Investigate Efimosfermin Alfa in Participants With Biopsy-confirmed F2- or F3-stage MASH

Purpose

The purpose of this study is to assess the safety and efficacy of efimosfermin alfa in the resolution of steatohepatitis and improvement of liver-related clinical outcome compared to placebo in individuals with MASH and biopsy-confirmed F2- or F3-stage fibrosis.

Condition

Non-alcoholic Fatty Liver Disease

Eligibility

Eligible Ages: Between 18 Years and 75 Years
Eligible Sex: All
Accepts Healthy Volunteers: No

Inclusion Criteria

Able and willing to understand and sign a written informed consent form that must be obtained prior to the initiation of study procedures 2. Age >=18 and <=75 years at enrollment 3. History or presence of 2 or more of the 5 components of metabolic syndrome per American Heart Association definition 4. Liver biopsy confirmation of MASH consistent with stage F2 or F3 fibrosis and a NAS score >=4 confirmed by a central pathologist

Exclusion Criteria

Contraindication or ineligibility for percutaneous liver biopsy 2. ALT or AST >=5 x upper limit of normal (ULN) 3. Total bilirubin >=1.3 milligram per deciliter (mg/dL). Individuals with documented Gilbert's syndrome may be enrolled if they experienced an isolated increase in total bilirubin of >=1.3 mg/dL and direct bilirubin is <=20% of total bilirubin; otherwise, the individual will be excluded. 4. Serum albumin <=3.5 grams per deciliter (g/dL) 5. International normalized ratio (INR) >=1.3 not due to therapeutic anticoagulation. Individuals receiving chronic anticoagulant treatment with higher INR values may be enrolled at the discretion of the Investigator and Study Medical Monitor. 6. Alkaline phosphatase (ALP) >=2*ULN 7. Platelet (PLT) count <140,000 per (/) cubic millimeter (mm^3); individuals with a PLT count between 110,000/mm^3 and 140,000/mm^3 may be enrolled after discussion with the Study Medical Monitor. 8. Serum creatinine >=1.5 mg/dL or creatinine clearance <=60 milliliter (mL)/minute (min)/1.73 square meter by Chronic Kidney Disease Epidemiology Collaboration equation 9. Alpha-fetoprotein >=20 nanogram per milliliter (ng/mL) 10. Glycated hemoglobin >=9.0% 11. Model for End-Stage Liver Disease score >=12 unless the score is elevated in the absence of liver dysfunction (e.g., Gilbert's syndrome) 12. Phosphatidyl ethanol (PEth) >=80 ng/mL at Screening 13. Evidence of infection with any of the following: 1. Human immunodeficiency virus; 2. Hepatitis B virus (detectable HBsAg at Screening); 3. Hepatitis C virus (HCV); 14. Chronic liver disease from any other cause including, but not limited to, alcoholic liver disease; evidence of portal hypertension; viral hepatitis or any history or evidence of cirrhosis on screening liver biopsy; or decompensated liver disease such as clinical ascites, bleeding gastroesophageal varices, hepatorenal syndrome, or hepatic encephalopathy prior to Screening or Day 1. 15. Current or history of excessive alcohol intake for >=3 months within the 12-month period prior to Screening

Study Design

Phase: Phase 3
Study Type: Interventional
Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Masking: Double (Participant, Investigator)
Masking Description: This is a double blind study.