Last updated: 10/29/2025 13:20:25
A pivotal clinical study to investigate efimosfermin alfa in participants with biopsy-confirmed F2- or F3-stage MASHZENITH-1
GSK study ID
301160
Clinicaltrials.gov ID
EudraCT ID
Not applicable
EU CT Number
Trial status
Recruiting
Recruiting
Trial overview
Official title: A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study to Investigate the Safety and Efficacy of Efimosfermin Alfa in Participants With Biopsy-Confirmed F2- or F3-Stage Metabolic Dysfunction-Associated Steatohepatitis (MASH) (ZENITH-1)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Proportion of participants experiencing improvement in fibrosis by >=1 stage and no worsening of steatohepatitis at Week 52
Timeframe: At Week 52
Proportion of participants experiencing resolution of steatohepatitis reading and no worsening of MASH CRN fibrosis score at Week 52
Timeframe: At Week 52
Time from randomization to an adjudicated composite liver-related clinical outcome
Timeframe: From Randomization (Day 1) to 48 months
Secondary outcomes:
Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity
Timeframe: At Week 52 and at Month 48
Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity
Timeframe: At Week 52 and at Month 48
Number of participants with Grade 3 and Grade 4 laboratory abnormalities
Timeframe: At Week 52 and at Month 48
Proportion of participants experiencing resolution of steatohepatitis on overall histopathological reading and improvement in liver fibrosis of >=1 stage at Week 52
Timeframe: At Week 52
Proportion of participants experiencing improvement in fibrosis by >=1 stage and no worsening of Steatohepatitis at Month 48
Timeframe: At Month 48
Proportion of participants experiencing improvement in fibrosis by >=2 stage and no worsening of Steatohepatitis at Week 52 and Month 48
Timeframe: At Week 52 and Month 48
Proportion of participants experiencing resolution of steatohepatitis reading and no worsening of MASH CRN score at Month 48
Timeframe: At Month 48
Absolute change from Baseline in vibration-controlled transient elastography-liver stiffness measurement (VCTE-LSM)
Timeframe: Baseline (Day 1), Week 52 and Month 48
Percent Change from Baseline in VCTE-LSM
Timeframe: Baseline (Day 1), Week 52 and Month 48
Absolute change from Baseline in controlled attenuation parameter (CAP) scores
Timeframe: Baseline (Day 1), Week 52 and Month 48
Percent Change from Baseline in CAP scores
Timeframe: Baseline (Day 1), Week 52 and Month 48
Proportion of participants achieving Change from Baseline in VCTE-LSM >=30 percent (%) at Week 52 and Month 48
Timeframe: Baseline (Day 1), Week 52 and Month 48
Absolute change from Baseline in magnetic resonance elastography (MRE) scores
Timeframe: Baseline (Day 1), Week 52 and Month 48
Percent Change from Baseline in MRE Score
Timeframe: Baseline (Day 1), Week 52 and Month 48
Absolute change from Baseline in Enhanced Liver Fibrosis (ELF) Score
Timeframe: Baseline (Day 1), Week 52 and Month 48
Percent Change from Baseline in ELF Score
Timeframe: Baseline (Day 1), Week 52 and Month 48
Proportion of participants experiencing improvement in ELF score of >=0.5
Timeframe: At Week 52 and Month 48
Absolute change from Baseline in hepatic fat fraction (HFF) by MRI-derived proton density fat fraction (PDFF)
Timeframe: Baseline (Day 1), Week 52 and Month 48
Percent Change from Baseline in HFF by MRI-PDFF
Timeframe: Baseline (Day 1), Week 52 and Month 48
Absolute change from Baseline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (International units per liter)
Timeframe: Baseline (Day 1), Week 52 and Month 48
Percent Change from Baseline in ALT and AST (International units per liter)
Timeframe: Baseline (Day 1), Week 52 and Month 48
Absolute change from Baseline in ALT and AST ratio (ALT/AST)
Timeframe: Baseline (Day 1), Week 52 and Month 48
Percent Change from Baseline in ALT and AST ratio (ALT/AST)
Timeframe: Baseline (Day 1), Week 52 and Month 48
Proportion of participants experiencing ALT and HFF normalization at Week 52 and Month 48
Timeframe: At Week 52 and Month 48
Proportion of participants experiencing HFF <=5% at Week 52 and Month 48
Timeframe: At Week 52 and Month 48
Change from Baseline in glycated hemoglobin (HbA1c) (Percentage of HbA1c) in participants with Type 2 Diabetes Mellitus (T2DM)
Timeframe: Baseline (Day 1), Week 52 and Month 48
Change from Baseline in body weight (kilograms)
Timeframe: Baseline (Day 1), Week 52 and Month 48
Change from Baseline in fasting total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)- cholesterol, and triglycerides (Millimoles per liter)
Timeframe: Baseline (Day 1), Week 52 and Month 48
Proportion of participants with antidrug and antiFGF21 antibody (ADA)
Timeframe: At Week 52 and Month 48
Change from Baseline in Chronic Liver Disease Questionnaire-Nonalcoholic Steatohepatitis (CLDQ-NASH) in domain and total score
Timeframe: Baseline (Day 1), Week 52 and Month 48
Change from Baseline in Short Form-36 (SF-36) component and domain scores at Week 52 and Month 48
Timeframe: Baseline (Day 1), Week 52 and Month 48
Serum drug Concentration of efimosfermin alfa
Timeframe: Up to Month 48
Maximum serum drug concentration (Cmax) of efimosfermin alfa
Timeframe: Up to Month 48
Area under the serum concentration-time curve (AUC) of efimosfermin alfa
Timeframe: Up to Month 48
Average serum drug concentration (Cavg) of efimosfermin alfa
Timeframe: Up to Month 48
Serum concentration of study drug at the end of the dosing interval (Ctrough) of efimosfermin alfa
Timeframe: Up to Month 48
Exposure-response relationship for efimosfermin alfa
Timeframe: Baseline (Day 1), Week 52 and Month 48
Interventions:
Enrollment:
1200
Primary completion date:
2028-29-03
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Non-alcoholic Fatty Liver Disease
Product
Not applicable
Collaborators
Not applicable
Study date(s)
October 2025 to December 2031
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18 - 75 Years
Accepts healthy volunteers
No
- 1. 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
- 1. Contraindication or ineligibility for percutaneous liver biopsy
- 2. ALT or AST >=5*upper limit of normal (ULN)
Inclusion and exclusion criteria
Inclusion criteria:
- 1. 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:
- 1. Contraindication or ineligibility for percutaneous liver biopsy 2. ALT or AST >=5*upper limit of normal (ULN) 3. Total bilirubin (BILI) >=1.3 milligram per deciliter (mg/dL). Individuals with documented Gilbert’s syndrome may be enrolled if they experienced an isolated increase in total BILI of >=1.3 mg/dL and direct BILI is <=20% of total BILI; 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. Known co-infection with any of the following: a. Human immunodeficiency virus; b. Hepatitis B virus; c. Hepatitis C virus (HCV); d. Hepatitis D virus; or e. Hepatitis E virus. 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
Trial location(s)
Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
Recruiting
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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