A Clinical Study to Investigate the Safety and Tolerability of Efimosfermin Alfa Injection in Participants With Known or Suspected F2- or F3-stage MASH

Phase 3RecruitingNCT07221188

GlaxoSmithKline1,250 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

1,250

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Efimosfermin AlfaDRUG

Efimosfermin Alfa will be administered

PlaceboDRUG

Placebo will be administered

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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 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. * 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

Locations (6)

GSK Investigational Site

Miami, Florida, United States

RECRUITING

GSK Investigational Site

Miami, Florida, United States

RECRUITING

GSK Investigational Site

Ocala, Florida, United States

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

Absolute Change from Baseline in enhanced liver fibrosis (ELF) score

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.

Time frame: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in ELF score

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.

Time frame: Baseline (Day 1) and up to Week 52

Number of participants achieving an improvement in ELF score greater than equal to 0.5

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.

Central Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718 GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

GSK Investigational Site

St Louis, Missouri, United States

RECRUITING

GSK Investigational Site

San Antonio, Texas, United States

RECRUITING

GSK Investigational Site

Waco, Texas, United States

RECRUITING

Time frame: At Week 52

Absolute Change from Baseline in vibration-controlled transient elastography (VCTE)- liver stiffness measurement (LSM) scores

Time frame: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in VCTE- LSM scores

Time frame: Baseline (Day 1) and up to Week 52

Number of participants achieving a change from Baseline in VCTE-LSM >=30 percentage (%)

Time frame: Baseline (Day 1) and up to Week 52

Absolute Change from Baseline in magnetic resonance elastography (MRE) scores in the subset of participants

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.

Time frame: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in the subset of participants with magnetic resonance elastography (MRE) scores

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.

Time frame: 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)

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.

Time frame: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in HFF by MRI-PDFF

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.

Time frame: Baseline (Day 1) and up to Week 52

Absolute Change from Baseline in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (International units per liter)

Time frame: Baseline (Day 1) and up to Week 52

Absolute Change from Baseline in ALT and AST ratio (ALT/AST)

Time frame: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in ALT and AST (International units per liter)

Time frame: Baseline (Day 1) and up to Week 52

Percent Change from Baseline in ALT and AST ratio (ALT/AST)

Time frame: Baseline (Day 1) and up to Week 52

Number of participants achieving ALT and HFF normalization

Time frame: At Week 52

Number of participants achieving HFF less than equal to (<=) 5%

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.

Time frame: At Week 52

Change from Baseline in glycated hemoglobin (HbA1c) for participants with type 2 diabetes mellitus (T2DM)

Time frame: Baseline (Day 1) and up to Week 52

Change from Baseline in body weight for all participants(kilograms)

Time frame: 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)

Time frame: 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

Time frame: At Week 52

Maximum serum drug concentrations (Cmax) of efimosfermin alfa

Time frame: Up to Week 52

Area under the serum concentration-time curve (AUC) of efimosfermin alfa

Time frame: Up to Week 52

Average serum drug concentration (Cavg) of efimosfermin alfa

Time frame: Up to Week 52

Serum concentration of study drug at the end of the dosing interval (Ctrough) of efimosfermin alfa

Time frame: Up to Week 52

Exposure-response relationship for efimosfermin alfa

To evaluate the correlation between pharmacokinetics (PK) derived from plasma concentrations, and biomarker responses, safety, and efficacy.

Time frame: Baseline (Day 1) and up to Week 52