A Study Evaluating the Efficacy and Safety of Pegozafermin in Participants With MASH and Fibrosis (ENLIGHTEN-Fibrosis)

Phase 3

Recruiting

• Conditions: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASH) / Nonalcoholic Steatohepatitis (NASH) With Fibrosis
• Interventions: Other: Placebo; Biological: Pegozafermin

• Registration Number: NCT06318169
• Lead Sponsor: 89bio, Inc.

Brief Summary

The study will assess the efficacy and safety of 2 dose regimens of pegozafermin for the treatment of liver fibrosis stage 2 or 3 in adult participants with MASH (previously known as nonalcoholic steatohepatitis \[NASH\]).

Detailed Description

Not available

Study Timeline

• Study Start: 2024-03-13
• Study First Submitted: 2024-03-13
• Study First Submitted QC: 2024-03-13
• Study First Posted: 2024-03-19
• Status Verified: 2025-03
• Last Update Submitted: 2025-05-07
• Last Update Posted: 2025-05-08
• Primary Completion: 2029-02
• Study Completion: 2029-02

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1050

Inclusion Criteria

• Males or non-pregnant females aged between 18 and 80 years (inclusive) at time of signing the informed consent form (ICF)
• Biopsy-confirmed MASH (previously named NASH) with fibrosis stage F2 or F3 per NASH clinical research network (CRN) System and NAS ≥4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation or NAS <4 and/or a ballooning degradation score of 0 with fibrosis stage F3 and a score of at least 1 in steatosis. A historical biopsy must be within 6 months of screening visit (with additional requirements).
• Body mass index (BMI) at screening ≥25.0 kilograms (kg)/meters squared (m^2) (≥23 kg/m^2 for Asian countries)

Key

Exclusion Criteria

• Chronic liver diseases other than MASH/NASH
• Evidence of cirrhosis on screening liver biopsy
• Have type 1 diabetes or poorly controlled type 2 diabetes
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥250 units per liter (U/L)
• Participants taking vitamin E (>400 international units [IU]/day) or pioglitazone must be on stable dose for at least 6 months prior to screening

Other inclusion and exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Matched Placebo will be administered in Regimens 1 and 2.
Pegozafermin Regimen 1	Pegozafermin	-
Pegozafermin Regimen 2	Pegozafermin	-

Primary Outcome Measures

Name	Time	Method
Proportion of Participants With at Least an Improvement of Fibrosis ≥1 Stage Without Worsening of MASH/NASH at Week 52	Week 52	Worsening of NASH is defined as increase in non-alcoholic fatty liver disease (NAFLD) Activity Score (NAS) for ballooning, inflammation, or steatosis
Proportion of Participants With MASH/NASH Resolution Without Worsening of Fibrosis at Week 52	Week 52	Resolution of NASH is defined as total absence of ballooning (score=0) and absent or mild inflammation (score 0 to 1). Worsening of fibrosis is defined as progression of fibrosis by ≥1 stage.
Time to First Occurrence of Disease Progression	Up to 240 weeks	Final analysis of the time to first occurrence of disease progression will be measured by a composite of protocol-specified clinical events

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Liver Fat as Assessed by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 52	Baseline, Week 52
Change from Baseline in Alanine Aminotransferase (ALT) at Week 52 and Month 36	Baseline, Week 52

Trial Locations

Locations (1)

89bio Clinical Study Site; 🇬🇧 York, United Kingdom