Metabolic Dysfunction-associated Steatohepatitis
Conditions
Keywords
Efimosfermin alfa, Metabolic dysfunction-associated, steatohepatitis, Fibrosis, Cirrhosis
Brief summary
This study will investigate the safety and efficacy of efimosfermin alfa in participants with compensated cirrhosis due to MASH.
Interventions
Efimosfermin alfa (subcutaneous injection) will be administered.
DRUGPlacebo
Placebo (subcutaneous injection) will be administered.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
This is a double-blind study.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Participants aged between 18 and 75 years at enrollment. * Participants with compensated cirrhosis due to MASH, confirmed by non-invasive assessments. * Participants with history or presence of at least two components of metabolic syndrome.
Exclusion criteria
* Participants with other chronic liver diseases. * Participants with evidence or history of decompensated liver disease or hepatocellular carcinoma. * Participants with history of Type 1 diabetes mellitus or major Type 2 diabetes complications. * Participants with history or evidence of chronic pancreatic disease; pancreatic injury or acute pancreatitis within 6 months before screening. * Participants with a recent history or planned surgical procedures or medications intended to produce significant weight loss. * Participants with alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>=5 times upper limit normal (ULN). * Participants with current or history of excessive alcohol intake.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time from randomization to an adjudicated composite liver-related clinical outcome | From Randomization (Day 1) to Week 356 (end of treatment) | Liver-related outcome comprises all-cause mortality; liver transplantation; occurrence of significant hepatic decompensation events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving change from Baseline in vibration-controlled transient elastography- liver stiffness measurement (VCTE-LSM) and in enhanced liver fibrosis (ELF) score | Baseline (Day 1), Week 96, and Week 260 | 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. |
| Proportion of participants achieving change from Baseline in VCTE-LSM | Baseline (Day 1), Week 96, and Week 260 | VCTE-LSM is a non-invasive test that uses vibration-controlled transient elastography to measure the stiffness of the liver in kPa. |
| Proportion of participants with treatment-emergent adverse events (TEAEs) and TEAEs by severity | 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 | Week 96, Week 260 and Week 356 (end of treatment) | — |
| Proportion of participants with Grade 3 and Grade 4 laboratory abnormalities | Week 96, Week 260 and Week 356 (end of treatment) | — |
| Absolute change from Baseline in VCTE-LSM | Baseline (Day 1), Week 96, Week 260, and Week 356 (end of treatment) | — |
| Relative change from Baseline in VCTE-LSM | Baseline (Day 1), Week 96, Week 260, and Week 356 (end of treatment) | — |
| Absolute change from Baseline in Magnetic resonance elastography (MRE) scores | Baseline (Day 1), Week 96, and Week 260 | 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. |
| Relative change from Baseline in MRE scores | Baseline (Day 1), Week 96, and Week 260 | 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 |
| Absolute change from Baseline in ELF scores | Baseline (Day 1), Week 96, Week 260, and Week 356 (end of treatment) | 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. |
| Relative change from Baseline in ELF scores | Baseline (Day 1), Week 96, Week 260, and Week 356 (end of treatment) | 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. |
| Proportion of participants experiencing improvement in ELF score | Week 96, Week 260 and Week 356 (end of treatment) | 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. |
| Change from Baseline in glycated hemoglobin (HbA1c) (Percentage of HbA1c) in participants with Type 2 Diabetes Mellitus (T2DM) | 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 | 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) | 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 | Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment) | 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. |
| Change from Baseline in Chronic Liver Disease Questionnaire-Nonalcoholic Steatohepatitis (CLDQ-NASH) domain and total score | Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment) | 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. |
| Change from Baseline in Short Form-36 (SF-36) component and domain scores | Baseline (Day 1), Week 96, Week 260 and Week 356 (end of treatment) | 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. |
Countries
Japan, United States
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Outcome results
None listed