This study will investigate the safety and efficacy of efimosfermin alfa in participants with compensated cirrhosis due to MASH.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
1,740
Efimosfermin alfa (subcutaneous injection) will be administered.
Placebo (subcutaneous injection) will be administered.
GSK Investigational Site
Miami, Florida, United States
RECRUITINGGSK Investigational Site
Miami, Florida, United States
RECRUITINGGSK Investigational Site
Dallas, Texas, United States
Time from randomization to an adjudicated composite liver-related clinical outcome
Liver-related outcome comprises all-cause mortality; liver transplantation; occurrence of significant hepatic decompensation events.
Time frame: From Randomization (Day 1) to Week 356 (end of treatment)
Proportion of participants achieving change from Baseline in vibration-controlled transient elastography- liver stiffness measurement (VCTE-LSM) and in enhanced liver fibrosis (ELF) score
VCTE-LSM is a non-invasive test that uses vibration-controlled transient elastography to measure the stiffness of the liver in kiloPascal (kPa). ELF score (scale of 6.7 to 11.3 with higher scores indicative of increased fibrosis) is a blood-based noninvasive test used as a prognostic marker for disease progression.
Time frame: Baseline (Day 1), Week 96, and Week 260
Proportion of participants achieving change from Baseline in VCTE-LSM
VCTE-LSM is a non-invasive test that uses vibration-controlled transient elastography to measure the stiffness of the liver in kPa.
Time frame: Baseline (Day 1), Week 96, and Week 260
Proportion of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity
Time frame: Week 96, Week 260 and Week 356 (end of treatment)
Proportion of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity
Time frame: Week 96, Week 260 and Week 356 (end of treatment)
Proportion of participants with Grade 3 and Grade 4 laboratory abnormalities
Time frame: Week 96, Week 260 and Week 356 (end of treatment)
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GSK Investigational Site
Humble, Texas, United States
RECRUITINGGSK Investigational Site
San Antonio, Texas, United States
RECRUITINGGSK Investigational Site
Ōgaki, Gifu, Japan
RECRUITINGGSK Investigational Site
Kawasaki-shi, Japan
RECRUITINGAbsolute change from Baseline in VCTE-LSM
Time frame: Baseline (Day 1), Week 96, Week 260, and Week 356 (end of treatment)
Relative change from Baseline in VCTE-LSM
Time frame: Baseline (Day 1), Week 96, Week 260, and Week 356 (end of treatment)
Absolute change from Baseline in Magnetic resonance elastography (MRE) scores
MRE is a non-invasive imaging technique that combines magnetic resonance imaging (MRI) scanning with low-frequency mechanical vibrations to measure the stiffness of liver. MRE scores less than (\<) 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 greater than (\>) 5.0 Stage 4 fibrosis.
Time frame: Baseline (Day 1), Week 96, and Week 260
Relative change from Baseline in MRE scores
MRE is a non-invasive imaging technique that combines 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), Week 96, and Week 260
Absolute change from Baseline in ELF scores
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 greater than or equal to (\>=) 11.3: High risk of progression.
Time frame: Baseline (Day 1), Week 96, Week 260, and Week 356 (end of treatment)
Relative change from Baseline in ELF scores
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), Week 96, Week 260, and Week 356 (end of treatment)
Proportion of participants experiencing improvement 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: Week 96, Week 260 and Week 356 (end of treatment)
Change from Baseline in glycated hemoglobin (HbA1c) (Percentage of HbA1c) in participants with Type 2 Diabetes Mellitus (T2DM)
Time frame: Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment)
Change from Baseline in fasting glucose (Millimole per Liter) in participants with T2DM
Time frame: Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment)
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), Week 96, Week 260 and Week 356 (end of treatment)
Change from Baseline in Patient-reported outcomes measurement information system (PROMIS)-Fatigue score
PROMIS-Fatigue is designed to assess fatigue-related symptoms (i.e., tiredness, exhaustion, mental tiredness, and lack of energy) and associated impacts on daily activities (i.e., activity limitations related to work, self-care, and exercise) over 7 items with a recall period of the previous 7 days. The items will be scored on a 5-point verbal rating scale (VRS) ranging from 1 (never) to 5 (always). Item scores are summed to generate a raw total score that ranges from 7 to 35, with higher scores indicates greater fatigue.
Time frame: Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment)
Change from Baseline in Chronic Liver Disease Questionnaire-Nonalcoholic Steatohepatitis (CLDQ-NASH) domain and total score
CLDQ-NASH is a NASH-specific health-related quality of life (HRQoL) Patient-Reported Outcomes (PRO) designed to assess 6 health domains over 36 items: abdominal symptoms (3 items), activity/energy (5 items), emotional health (9 items), fatigue (6 items), systemic symptoms (6 items) and worry (7 items). The domain scores range from 1 to 7, higher scores indicating better HRQoL. A score of 1 meaning the symptom being assessed is "present always" while a score of 7 means the symptom is "never present". The total score can range from 36 to 252, a higher score corresponds to a better quality of life while a lower score corresponds to a worse quality of life.
Time frame: Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment)
Change from Baseline in Short Form-36 (SF-36) component and domain scores
SF-36 is a generic HRQoL PRO designed to assess 8 health domains over 36 items: physical functioning (10 items), bodily pain (2 items), role limitations due to physical problems (4 items), role limitations due to emotional problems (3 items), general health (5 items), mental health (5 items), social functioning (2 items), and vitality (4 items). Each domain is scored from 0 (poorer health) to 100 (better health). SF-36 is scored into 8 domains and 2 component scores: physical component summary (PCS) and mental component summary (MCS). The domain and component scores range from 0 to 100, with higher scores indicating better HRQoL.
Time frame: Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment)