CTRI/2025/09/095241 [Registered on: 22/09/2025] Trial Registered Prospectively
Last Modified On:
01/04/2026
Post Graduate Thesis
No
Type of Trial
Interventional
Type of Study
Drug
Study Design
Other
Public Title of Study
A study evaluating the efficacy and safety of Pegozafermin for the treatment of liver fibrosis in adult participants with MASH (previously known as non-alcoholic steatohepatitis [NASH])
Scientific Title of Study
A Phase 3 Study to Evaluate the Efficacy and Safety of Pegozafermin in Subjects with Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Fibrosis
Trial Acronym
The ENLIGHTEN-Fibrosis Study
Secondary IDs if Any
Secondary ID
Identifier
BIO89-100-131 Version 2.0 dated 16 January 2025
Protocol Number
NCT06318169
ClinicalTrials.gov
Details of Principal Investigator or overall Trial Coordinator (multi-center study)
Name
Designation
Affiliation
Address
Phone
Fax
Email
Details of Contact Person Scientific Query
Name
Supriya Parui
Designation
Regulatory Submission Coordinator
Affiliation
Medpace Clinical Research India Pvt. Ltd
Address
Unit Number 1203, 12th Floor,
Bldg.Q2, Aurum Q2 Parc, Gen 4/1, TTC,Thane Belapur Road,
Navi Mumbai
Thane MAHARASHTRA 400710 India
Phone
9773922367
Fax
Email
s.parui@medpace.com
Details of Contact Person Public Query
Name
Supriya Parui
Designation
Regulatory Submission Coordinator
Affiliation
Medpace Clinical Research India Pvt. Ltd
Address
Unit Number 1203, 12th Floor,
Bldg.Q2, Aurum Q2 Parc, Gen 4/1, TTC,Thane Belapur Road,
Navi Mumbai
MAHARASHTRA 400710 India
Phone
9773922367
Fax
Email
s.parui@medpace.com
Source of Monetary or Material Support
89bio, Inc.655 Montgomery Street, 15th Floor San Francisco CA 94111, US
Primary Sponsor
Name
89bio, Inc.
Address
655 Montgomery Street, 15th Floor San Francisco CA 94111, US
Type of Sponsor
Pharmaceutical industry-Global
Details of Secondary Sponsor
Name
Address
Medpace Clinical Research India Pvt Ltd
Unit Number 1203, 12th Floor, Bldg.Q2, Aurum Q Parc, Gen 4/1, TTC,
Thane Belapur Road,
Navi Mumbai – 400710, Maharashtra, India
Countries of Recruitment
Argentina Australia Austria Belgium Bulgaria Canada Czech Republic France Georgia Germany Hong Kong Israel Italy Japan Mexico Netherlands Poland Republic of Korea Singapore South Africa Spain Taiwan Turkey United Kingdom United States of America
Sites of Study
No of Sites = 9
Name of Principal
Investigator
Name of Site
Site Address
Phone/Fax/Email
Dr Vijendra Kirnake
Acharya Vinoba Bhave Rural Hospital, Datta Meghe Institute of
"Institutional Ethics Committee Institute of Medical Sciences, Banaras Hindu University, Varanasi-221005, Uttar Pradesh, India ECR/526/Inst/UP/2014/RR-20"
Submittted/Under Review
Crescent Hospital Institutional Ethics Committee
Approved
Human Research Ethics Committee, Indian Institute of Liver and Digestive Sciences
Approved
Institutional Ethics Committee Post Graduate Institute of Medical Education & Research (PGIMER), IEC office Room No. 6006, 6th Floor, PN Chuttani block, PGIMER, Sector 12, Chandigarh, 160012, India ECR/25/Inst/CH/2013/RR-20"
Submittted/Under Review
Institutional Ethics Committee of DMIHER, Administrative Block, University Office, Datta Meghe Institute of Higher Education & Research Sawangi (Meghe), Wardha 442107, Maharashtra, India ECR/440/Inst/MH/2013/RR-24
Approved
Institutional Ethics Committee, GMCH Gauhati Medical College and Hospital
Approved
Institutional Ethics Committee-KIMS, Kalinga Institute of Medical Sciences, Kushabhadra campus, 5, KIIT Road, Patia, Bhubaneswar, Odisha - 751024 India
Approved
Instituttional Ethics Committee All India Institute of Medical Sciences, Bhubaneswar, Sijua, Patrapada, Dumduma, Odisha 751019, India
Submittted/Under Review
Prime Hospital Institutional Ethics Committee, Panchvati Society Main Road, Atithi Chowk, Beside Chandresh Vadi, Rajkot, Gujarat, 360001, India
Approved
Regulatory Clearance Status from DCGI
Status
Approved/Obtained
Health Condition / Problems Studied
Health Type
Condition
Patients
(1) ICD-10 Condition: K740||Hepatic fibrosis,
Intervention / Comparator Agent
Type
Name
Details
Intervention
pegozafermin
Pegozafermin is a glycoPEGylated FGF21 analog that contains an N-terminal methionine residue, 2-point mutations, and a single 20 kDa linear PEG covalently attached via a glycosyl moiety at the threonine residue at position 173.
On Randomization Day (Day 1), approximately 1050 eligible subjects will be randomized 1:1:1 to one of the following treatment groups:
• Pegozafermin 30 mg, QW, SC, n equal to 350
• Pegozafermin 44 mg, Q2W, SC, n equal to 350
•Placebo, n equal to 350 (to be split as QW [n equal to 175] or Q2W [n equal to 175])
Comparator Agent
Placebo
20 mM Tris, 150 mM Arginine-HCl, and 0.2 mg/mL
polysorbate 80 at pH 7.5, is presented in 3 mL glass vial with 1.1 mL nominal fill volume or in 1mL
pre-filled syringes at 1.0 mL and 0.5 mL nominal fill volumes.
Inclusion Criteria
Age From
18.00 Year(s)
Age To
80.00 Year(s)
Gender
Both
Details
-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) either through a historical biopsy or a biopsy at Screening in
a. Group A Subjects with fibrosis stage F2 or F3 per NASH CRN system and NAS greater than or equal to 4, with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation.
b. Group B Subjects who do not meet NAS criteria for Group A and have F3 fibrosis and a score of at least 1 in steatosis. This will include subjects with NAS less than 4 and or a ballooning degradation score of 0.
A historical biopsy obtained within 6 months prior to first day of Screening (i.e., day ICF is signed) is acceptable if it is deemed suitable for interpretation and study-eligible by a central-read consensus and if the subject has had no significant change in metabolic status (control of diabetes, hyperlipidemia, or greater than 5 percent weight loss or gain).
-Body mass index (BMI) at Screening greater than or equal to 25.0 kg per m2 (greater than or equal to 23.0 kg per m2 for Asian countries).
ExclusionCriteria
Details
-Chronic liver diseases other than MASH
-Evidence of cirrhosis (NASH CRN fibrosis stage F4 on screening biopsy assessed by central read)
-Uncontrolled or newly diagnosed (less than or equal to 3 months since diagnosis) type 2 diabetes mellitus (T2DM).
a.Hemoglobin A1c (HbA1c) level greater than 9.5 percent at Screening.
b.Subjects who are on antidiabetic medications must be on a continuous regimen for greater than or equal to 3 months prior to Screening (6 months of a continuous regimen for glucagon-like peptide 1 (GLP-1) based therapies including GLP-1 agonists, GLP-1 or glucose-dependent insulinotropic polypeptide [GIP] dual agonists, and other GLP-1 combination treatments)
c.See Section 5.2 for further details on exclusion criterion.
-Type 1 diabetes mellitus
-Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than or equal to 250 Unit per litre
The full list with details of eligibility criteria is provided in Section 5 of Protocol.
Method of Generating Random Sequence
Stratified block randomization
Method of Concealment
Centralized
Blinding/Masking
Double Blind Double Dummy
Primary Outcome
Outcome
TimePoints
Proportion if participants with at least an improvement of Fibrosis greater than equal to 1 stage without worsening of MASH or NASH at week 52
Proportion if participants with MASH or NASH resolution without worsening of fibrosis at week 52
Time to first Occurance of Disease Progression
week 52
Secondary Outcome
Outcome
TimePoints
"Change from Baseline in Liver Fat as Assessed by Mangnetic Resonance imaging - Proton Density Fat Fraction (MRI-PDFF) at Week 52
Change from Baseline in Alanine Aminotransferase (ALT) at Week 52 and Month 36"
Baseline, week 52
Target Sample Size
Total Sample Size="1050" Sample Size from India="30" Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials" Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials"
Phase of Trial
Phase 3
Date of First Enrollment (India)
30/01/2026
Date of Study Completion (India)
Applicable only for Completed/Terminated trials
Date of First Enrollment (Global)
04/06/2024
Date of Study Completion (Global)
Applicable only for Completed/Terminated trials
Estimated Duration of Trial
Years="4" Months="11" Days="0"
Recruitment Status of Trial (Global)
Open to Recruitment
Recruitment Status of Trial (India)
Open to Recruitment
Publication Details
N/A
Individual Participant Data (IPD) Sharing Statement
Will individual participant data (IPD) be shared publicly (including data dictionaries)?
Response - NO
Brief Summary
This is a Phase 3, multicenter, randomized, double-blind, placebo-controlled study of pegozafermin for the treatment of liver fibrosis stage F2 or F3 in adult subjects with MASH.
The study is designed to assess the efficacy and safety of 2 dose regimens of pegozafermin, administered either weekly (QW) or once every 2 weeks (Q2W) in subjects with biopsy-confirmed NASH (NASH Clinical Research Network [CRN] system: F2 and F3) as further defined in the groups below.
The study will enroll subjects in 2 groups:
(1) Group A: Subjects with F2 or F3 fibrosis and a NAS greater than equal to 4 with a score of at least 1 in each of steatosis, ballooning degeneration, and lobular inflammation. Group A will comprise approximately 840 subjects.
(2) Group B: Subjects who do not meet NAS criteria for group A and have F3 fibrosis and a score of at least 1 in steatosis. Group B will comprise approximately 210 subjects.
Pegozafermin is a glycoPEGylated (PEG; polyethylene glycol) analog of fibroblast growth factor 21 (FGF21). FGF21 is a member of the fibroblast growth factor (FGF) endocrine subfamily and contributes to the regulation of glucose and lipid metabolism. FGF21 increases adipose and hepatic insulin sensitivity, suppresses lipolysis and non-esterified fatty acid (NEFA) release from adipocytes, and reduces serum NEFA and liver triglyceride (TG) levels
This study will assess the effect of pegozafermin on the histological surrogate endpoints at Interim Analysis (IA) at 52 weeks, and clinical outcome at the event-driven.