A Clinical Study to Investigate the Safety and Tolerability of Efimosfermin Alfa Injection in Participants With Known or Suspected F2- or F3-stage MASH
- 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.
- Acronym
- ZENITH-2
- 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
- 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)
- Control arm
- Placebo
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Recruiting
- Phase
- Phase 3
- Study type
- Interventional
- Completion date
- 2028-03-24
- First posted
- 2025-10-27
- Registry last updated
- 2026-07-27
- Primary completion date
- 2028-03-24
- Start date
- 2025-12-12
- Participants
- 1,250
- Participant count basis
- Estimated
- Planned participants
- 1,250
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- GlaxoSmithKline
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT07221188
- ClinicalTrials.gov ID
- NCT07221188
- Registry record
- Open registry record
- Allocation
- Randomised
- Model
- Parallel groups
- Purpose
- Treatment
- Masking
- Double masking
- Masking description
- This is a double blind study.
- Masked roles
- Participants, Investigators
Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity
Timeframe: At Week 52
Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity
Timeframe: At Week 52
Number of participants with Grade 3 and Grade 4 laboratory abnormalities
Timeframe: At Week 52
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.
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.
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.
Absolute Change from Baseline in vibration-controlled transient elastography (VCTE)- liver stiffness measurement (LSM) scores
Timeframe: Baseline (Day 1) and up to Week 52
Percent Change from Baseline in VCTE- LSM scores
Timeframe: Baseline (Day 1) and up to Week 52
Number of participants achieving a change from Baseline in VCTE-LSM >=30 percentage (%)
Timeframe: Baseline (Day 1) and up to Week 52
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.
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.
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.
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.
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
Absolute Change from Baseline in ALT and AST ratio (ALT/AST)
Timeframe: Baseline (Day 1) and up to Week 52
Percent Change from Baseline in ALT and AST (International units per liter)
Timeframe: Baseline (Day 1) and up to Week 52
Percent Change from Baseline in ALT and AST ratio (ALT/AST)
Timeframe: Baseline (Day 1) and up to Week 52
Number of participants achieving ALT and HFF normalization
Timeframe: At Week 52
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.
Change from Baseline in glycated hemoglobin (HbA1c) for participants with type 2 diabetes mellitus (T2DM)
Timeframe: Baseline (Day 1) and up to Week 52
Change from Baseline in body weight for all participants(kilograms)
Timeframe: Baseline (Day 1) and up to Week 52
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
Number of Participants with antidrug and anti-fibroblast growth factor 21 (FGF21) antibodies (ADA) at Week 52
Timeframe: At Week 52
Serum drug Concentration of efimosfermin alfa
Timeframe: Up to Week 52
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Maximum age
- 75 Years
- Healthy volunteers
- No
- 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
- 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
- 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.
- 2025
- 2025-523674-16
Related records
Drugs (1)
Lead sponsors (1)
Conditions (1)
- Metabolic dysfunction-associated steatotic liver disease Primary condition