NCT07221188RecruitingPhase 3
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)
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Sponsor
- GlaxoSmithKline
- Enrollment
- 1,250
- Locations
- 71
- Primary Endpoint
- Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity
Study Overview
Brief 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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Masking Description
This is a double blind study.
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts 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
- •Current or history of excessive alcohol intake for >=3 months within the 12-month period prior to Screening
Arms & Interventions
Placebo
Placebo Comparator
Participants randomized to this group will receive Placebo
Intervention: Placebo (Drug)
Efimosfermin Alfa Dose Level 1
Experimental
Participants randomized to this group will receive Efimosfermin Alfa at dose level 1
Intervention: Efimosfermin Alfa (Drug)
Efimosfermin Alfa Dose Level 2
Experimental
Participants randomized to this group will receive Efimosfermin Alfa at dose level 2
Intervention: Efimosfermin Alfa (Drug)
Outcomes
Primary Outcomes
Number of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity
Time Frame: At Week 52
Number of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity
Time Frame: At Week 52
Number of participants with Grade 3 and Grade 4 laboratory abnormalities
Time Frame: At Week 52
Secondary Outcomes
- Serum drug Concentration of efimosfermin alfa(Up to Week 52)
- Absolute Change from Baseline in enhanced liver fibrosis (ELF) score(Baseline (Day 1) and up to Week 52)
- Percent Change from Baseline in ELF score(Baseline (Day 1) and up to Week 52)
- Number of participants achieving an improvement in ELF score greater than equal to 0.5(At Week 52)
- Absolute Change from Baseline in vibration-controlled transient elastography (VCTE)- liver stiffness measurement (LSM) scores(Baseline (Day 1) and up to Week 52)
- Percent Change from Baseline in VCTE- LSM scores(Baseline (Day 1) and up to Week 52)
- Number of participants achieving a change from Baseline in VCTE-LSM >=30 percentage (%)(Baseline (Day 1) and up to Week 52)
- Absolute Change from Baseline in magnetic resonance elastography (MRE) scores in the subset of participants(Baseline (Day 1) and up to Week 52)
- Percent Change from Baseline in the subset of participants with magnetic resonance elastography (MRE) scores(Baseline (Day 1) and up to Week 52)
- Absolute Change from Baseline in hepatic fat fraction (HFF) by magnetic resonance imaging (MRI)- derived proton density fat fraction (PDFF)(Baseline (Day 1) and up to Week 52)
- Percent Change from Baseline in HFF by MRI-PDFF(Baseline (Day 1) and up to Week 52)
- Absolute Change from Baseline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (International units per liter)(Baseline (Day 1) and up to Week 52)
- Absolute Change from Baseline in ALT and AST ratio (ALT/AST)(Baseline (Day 1) and up to Week 52)
- Percent Change from Baseline in ALT and AST (International units per liter)(Baseline (Day 1) and up to Week 52)
- Percent Change from Baseline in ALT and AST ratio (ALT/AST)(Baseline (Day 1) and up to Week 52)
- Number of participants achieving ALT and HFF normalization(At Week 52)
- Number of participants achieving HFF less than equal to (<=) 5%(At Week 52)
- Change from Baseline in glycated hemoglobin (HbA1c) for participants with type 2 diabetes mellitus (T2DM)(Baseline (Day 1) and up to Week 52)
- Change from Baseline in body weight for all participants(kilograms)(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)(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(At Week 52)
- Maximum serum drug concentrations (Cmax) of efimosfermin alfa(Up to Week 52)
- Area under the serum concentration-time curve (AUC) of efimosfermin alfa(Up to Week 52)
- Average serum drug concentration (Cavg) of efimosfermin alfa(Up to Week 52)
- Serum concentration of study drug at the end of the dosing interval (Ctrough) of efimosfermin alfa(Up to Week 52)
- Exposure-response relationship for efimosfermin alfa(Baseline (Day 1) and up to Week 52)
Investigators
Study Sites (71)
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