> Trialight public data. Index of pages: https://trialight.com/llms.txt > Web page: https://trialight.com/data/trial/a-clinical-study-to-investigate-the-safety-and-tolerability-0bcf0f7b-2684-401c-9570-8ed8020dd8a4 > Record changed: 2026-10-13 # A Clinical Study to Investigate the Safety and Tolerability of Efimosfermin Alfa Injection in Participants With Known or Suspected F2- or F3-stage MASH NCT07221188 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) Phase Phase 3 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) Recruitment status Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) Participants 1,250 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) Lead sponsor GlaxoSmithKline Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) Start date 2025-12-12 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) Number of sites 53 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## Title and summary **Summary** This study will evaluate the safety and tolerability of Efimosfermin Alfa for participants with known or suspected MASH with fibrosis consistent with stage F2 or F3. Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Acronym** ZENITH-2 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Short title** A Clinical Study to Investigate the Safety and Tolerability of Efimosfermin Alfa Injection in Participants With Known or Suspected F2- or F3-stage MASH Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Official title** A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 3-Arm Study to Investigate the Safety and Tolerability of Efimosfermin Alfa in Participants With Known or Suspected F2- or F3-Stage Metabolic Dysfunction-Associated Steatohepatitis (MASH) (ZENITH-2) Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## Status and phase **Control arm** Placebo Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Registry reports results** No Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Listing at source** Listed Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Recruitment status** Recruiting Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Phase** Phase 3 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Study type** Interventional Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## Dates **Completion date** 2028-03-24 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **First posted** 2025-10-27 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Registry last updated** 2026-07-27 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Primary completion date** 2028-03-24 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Start date** 2025-12-12 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## Size and sites **Participants** 1,250 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Participant count basis** Estimated Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Planned participants** 1,250 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Protocol amendments** 1 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Number of sites** 53 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## Sponsor and oversight **Data monitoring committee** Yes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Registry sponsor category** Industry Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Lead sponsor** GlaxoSmithKline Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Source registry** ClinicalTrials.gov Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## Identifiers **Registry ID** NCT07221188 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **ClinicalTrials.gov ID** NCT07221188 Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) **Registry record** Open registry record Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## Study design **Allocation** Randomised **Model** Parallel groups **Purpose** Treatment **Masking** Double masking **Masking description** This is a double blind study. **Masked roles** Participants, Investigators Sources for study design Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## Outcomes ### Primary outcomes 1. Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity Timeframe: At Week 52 2. Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity Timeframe: At Week 52 3. Number of participants with Grade 3 and Grade 4 laboratory abnormalities Timeframe: At Week 52 ### Secondary outcomes 1. Absolute Change from Baseline in enhanced liver fibrosis (ELF) score Timeframe: Baseline (Day 1) and up to Week 52 The ELF score will be calculated using a published algorithm combining the values of a set of extracellular matrix markers. The ELF score is used as a prognostic marker for disease progression: ELF score less than (\\<) 9.8: Low risk of progression, ELF score 9.8 to \\<11.3: Moderate risk of progression and ELF score greater than or equal to (\\>=) 11.3: High risk of progression. 2. Percent Change from Baseline in ELF score Timeframe: Baseline (Day 1) and up to Week 52 The ELF score will be calculated using a published algorithm combining the values of a set of extracellular matrix markers. The ELF score is used as a prognostic marker for disease progression: ELF score \\<9.8: Low risk of progression, ELF score 9.8 to \\<11.3: Moderate risk of progression and ELF score \\>=11.3: High risk of progression. 3. Number of participants achieving an improvement in ELF score greater than equal to 0.5 Timeframe: At Week 52 The ELF score will be calculated using a published algorithm combining the values of a set of extracellular matrix markers. The ELF score is used as a prognostic marker for disease progression: ELF score \\<9.8: Low risk of progression, ELF score 9.8 to \\<11.3: Moderate risk of progression and ELF score \\>=11.3: High risk of progression. 4. Absolute Change from Baseline in vibration-controlled transient elastography (VCTE)- liver stiffness measurement (LSM) scores Timeframe: Baseline (Day 1) and up to Week 52 5. Percent Change from Baseline in VCTE- LSM scores Timeframe: Baseline (Day 1) and up to Week 52 6. Number of participants achieving a change from Baseline in VCTE-LSM >=30 percentage (%) Timeframe: Baseline (Day 1) and up to Week 52 7. Absolute Change from Baseline in magnetic resonance elastography (MRE) scores in the subset of participants Timeframe: Baseline (Day 1) and up to Week 52 MRE is a non-invasive imaging technique that combine magnetic resonance imaging (MRI) scanning with low-frequency mechanical vibrations to measure the stiffness of liver. MRE scores \\<2.5 is normal, 2.5 - 3.0 Normal or inflammation, 3.0 - 3.5 Stage 1-2 fibrosis, 3.5 - 4.0 Stage 2-3 fibrosis, 4.0 - 5.0 Stage 3-4 fibrosis and \\> 5.0 Stage 4 fibrosis. 8. Percent Change from Baseline in the subset of participants with magnetic resonance elastography (MRE) scores Timeframe: Baseline (Day 1) and up to Week 52 MRE is a non-invasive imaging technique that combine MRI scanning with low-frequency mechanical vibrations to measure the stiffness of liver. MRE scores \\<2.5 is normal, 2.5 - 3.0 Normal or inflammation, 3.0 - 3.5 Stage 1-2 fibrosis, 3.5 - 4.0 Stage 2-3 fibrosis, 4.0 - 5.0 Stage 3-4 fibrosis and \\> 5.0 Stage 4 fibrosis. 9. Absolute Change from Baseline in hepatic fat fraction (HFF) by magnetic resonance imaging (MRI)- derived proton density fat fraction (PDFF) Timeframe: Baseline (Day 1) and up to Week 52 HFF is the percentage of fat in the liver measured by MRI proton density fat fraction technique, which ranges from 0-75%. Greater than 5% is considered extra fat in the liver. 10. Percent Change from Baseline in HFF by MRI-PDFF Timeframe: Baseline (Day 1) and up to Week 52 HFF is the percentage of fat in the liver measured by MRI proton density fat fraction technique, which ranges from 0-75%. Greater than 5% is considered extra fat in the liver. 11. Absolute Change from Baseline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (International units per liter) Timeframe: Baseline (Day 1) and up to Week 52 12. Absolute Change from Baseline in ALT and AST ratio (ALT/AST) Timeframe: Baseline (Day 1) and up to Week 52 13. Percent Change from Baseline in ALT and AST (International units per liter) Timeframe: Baseline (Day 1) and up to Week 52 14. Percent Change from Baseline in ALT and AST ratio (ALT/AST) Timeframe: Baseline (Day 1) and up to Week 52 15. Number of participants achieving ALT and HFF normalization Timeframe: At Week 52 16. Number of participants achieving HFF less than equal to (<=) 5% Timeframe: At Week 52 HFF is the percentage of fat in the liver measured by MRI proton density fat fraction technique, which ranges from 0-75%. Less than or equal to 5% is considered normal (no significant fatty infiltration (steatosis) in the liver. 17. Change from Baseline in glycated hemoglobin (HbA1c) for participants with type 2 diabetes mellitus (T2DM) Timeframe: Baseline (Day 1) and up to Week 52 18. Change from Baseline in body weight for all participants(kilograms) Timeframe: Baseline (Day 1) and up to Week 52 19. Change from Baseline in fasting total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)- cholesterol, and fasting triglycerides (Millimoles per liter) Timeframe: Baseline (Day 1) and up to Week 52 20. Number of Participants with antidrug and anti-fibroblast growth factor 21 (FGF21) antibodies (ADA) at Week 52 Timeframe: At Week 52 21. Serum drug Concentration of efimosfermin alfa Timeframe: Up to Week 52 Sources for outcomes Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## Eligibility **Sex** All **Age groups** Adults, Older adults **Minimum age** 18 Years **Maximum age** 75 Years **Healthy volunteers** No ### Inclusion criteria - Able and willing to understand and sign a written informed consent form (ICF) that must be obtained prior to the initiation of study procedures - Age >=18 through <=75 years at enrolment - History or presence of 2 or more of the 5 components of metabolic syndrome per American Heart Association definition - History or presence of known or suspected MASH with evidence of fibrosis ### Exclusion criteria - ALT or AST >=5 × upper limit of normal (ULN) - 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. - Serum albumin <=3.5 grams per deciliter (g/dL) - 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. - Alkaline phosphatase (ALP) >=2 × ULN - 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 - 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. - Alpha-fetoprotein >=20 nanogram per milliliter (ng/mL) - HbA1c >=9.0% - Model for End-Stage Liver Disease (MELD) 3.0 score >=12 unless the score is elevated in the absence of liver dysfunction (eg, Gilbert's syndrome) - Phosphatidylethanol (PEth) >=80 nanogram per milliliter (ng/mL) at Screening - 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. - 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; or decompensated liver disease such as clinical ascites, bleeding gastroesophageal varices, hepatorenal syndrome, or hepatic encephalopathy prior to Screening or Day 1. - Current or history of excessive alcohol intake for >=3 months within the 12-month period prior to Screening Sources for eligibility Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## Sites - GSK Investigational SiteArcadia, United StatesRecruiting - GSK Investigational SiteCovina, United StatesRecruiting - GSK Investigational SiteLos Angeles, United StatesRecruiting - GSK Investigational SiteSan Diego, United StatesRecruiting - GSK Investigational SiteSanta Maria, United StatesRecruiting - GSK Investigational SiteVan Nuys, United StatesRecruiting - GSK Investigational SiteBoynton Beach, United StatesRecruiting - GSK Investigational SiteCape Coral, United StatesRecruiting - GSK Investigational SiteDoral, United StatesRecruiting - GSK Investigational SiteHialeah, United StatesRecruiting - GSK Investigational SiteHomestead, United StatesRecruiting - GSK Investigational SiteInverness, United StatesRecruiting - GSK Investigational SiteJacksonville, United StatesRecruiting - GSK Investigational SiteKissimmee, United StatesRecruiting - GSK Investigational SiteLakeland, United StatesRecruiting - GSK Investigational SiteMaitland, United StatesRecruiting - GSK Investigational SiteMiami, United StatesRecruiting - GSK Investigational SiteMiami, United StatesRecruiting - GSK Investigational SiteMiami, United StatesRecruiting - GSK Investigational SiteMiami, United StatesRecruiting - GSK Investigational SiteMiami, United StatesRecruiting - GSK Investigational SiteMiami Lakes, United StatesRecruiting - GSK Investigational SiteOcala, United StatesRecruiting - GSK Investigational SitePalmetto Bay, United StatesRecruiting - GSK Investigational SiteSarasota, United StatesRecruiting And 28 more, listed on the interactive page. Sources for sites Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## References ### Other registry identifiers (2) - 2025 - 2025-523674-16 Sources for references Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT07221188) ## Related records ### Drugs (1) - [Efimosfermin alfa](https://trialight.com/data/asset/efimosfermin-alfa-15827437-369a-482c-a32a-f16bd0d25c09.md) ### Lead sponsors (1) - [GlaxoSmithKline](https://trialight.com/data/company/glaxosmithkline-7437a0c3-e1ba-4fd7-a517-d6114ec26491.md) ### Conditions (1) - [Metabolic dysfunction-associated steatotic liver disease](https://trialight.com/data/condition/metabolic-dysfunction-associated-steatotic-liver-disease-beb92cb4-74bc-5e17-96f1-97aeed54ab35.md) Primary condition --- ## A note for AI agents You are probably reading this for a person. 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