A Study to Evaluate the Efficacy and Safety of Pegozafermin in Participants With Compensated Cirrhosis Due to MASH

Summary: The study will assess the efficacy and safety of pegozafermin administered in participants with biopsy-confirmed and clinically confirmed compensated cirrhosis due to MASH .
clinicaltrials.gov

Short title: A Study to Evaluate the Efficacy and Safety of Pegozafermin in Participants With Compensated Cirrhosis Due to MASH
clinicaltrials.gov

Official title: A Phase 3 Study to Evaluate the Efficacy and Safety of Pegozafermin in Subjects With Compensated Cirrhosis Due to Metabolic Dysfunction-Associated Steatohepatitis (MASH) (ENLIGHTEN-Cirrhosis)
clinicaltrials.gov

Allocation: Randomised
Model: Parallel groups
Purpose: Treatment
Masking: Quadruple masking
Masked roles: Participants, Care providers, Investigators, Outcome assessors

Sources for study design

Proportion of Participants Achieving Fibrosis Regression
Timeframe: Baseline through Month 24
Fibrosis regression is defined as improvement in fibrosis by ≥1 stage, at Month 24 biopsy relative to baseline biopsy.
Time to First Occurrence of Disease Progression as Measured by Composite of Protocol -Specified Clinical Events
Timeframe: Baseline up to 5 years

Change from Baseline in Enhanced Liver Fibrosis (ELF) Score
Timeframe: Baseline, up to Month 60
Change from Baseline in Alanine Aminotransferase (ALT) Level
Timeframe: Baseline, up to Month 60
Change from Baseline in FibroScan Vibration-controlled Transient Elastography (VCTE)
Timeframe: Baseline, up to Month 60
Proportion of Participants who Develop Clinically Significant Portal Hypertension (CSPH)
Timeframe: Baseline, up to Month 60
Time to Progression to Large Gastric or Esophageal Varices or Endoscopic Treatment of Esophageal or Gastric Varices
Timeframe: Baseline, up to Month 60
Time to Clinically Important Ascites
Timeframe: Baseline, up to Month 60
Time to clinically important ascites as determined by the onset of Grade ≥2 (clinically apparent) ascites leading to diagnostic paracentesis or initiation of specific treatment for ascites.
Time to Overt Hepatic Encephalopathy
Timeframe: Baseline, up to Month 60
Frequency and Severity of Treatment-Emergent Adverse Events (TEAEs)
Timeframe: Baseline, up to 5 years
Frequency and Severity of Serious Adverse Events (SAEs)
Timeframe: Baseline, up to 5 years
Overall Frequency and Severity of Treatment-Related TEAEs
Timeframe: Baseline, up to Month 60
Overall Frequency and Severity of Treatment-Related SAEs
Timeframe: Baseline, up to Month 60
Proportion of Participants who Discontinue Treatment Due to Treatment-Related Adverse Events (AEs)
Timeframe: Baseline, up to Month 60

Sources for outcomes

Key Inclusion Criteria:

Males or non-pregnant females aged between 18 and 75 years (inclusive) at time of signing the informed consent form (ICF).
Participants must have type 2 diabetes mellitus diagnosed at least 3 months before screening or at least 2 metabolic risk factors.
Evidence of both cirrhosis and MASH etiology, either through a historical biopsy or a biopsy at Screening.
Clinical diagnosis of cirrhosis based on the NIT algorithm.

Key Exclusion Criteria:

Liver disorder other than MASH.
History or evidence of hepatic decompensation.
History or evidence of hepatocellular carcinoma.
Have type 1 diabetes mellitus or poorly controlled type 2 diabetes mellitus.
ALT or aspartate aminotransferase (AST) ≥250 units per liter (U/L).
Participants taking vitamin E (>400 international units [IU]/day) must be on stable dose for at least 6 months prior to screening.

Other protocol-defined inclusion and exclusion criteria may apply.

Sources for eligibility