Metabolic Dysfunction-associated Steatohepatitis
Conditions
Keywords
Cirrhosis, Efimosfermin, Fibrosis, Metabolic dysfunction-associated, Steatohepatitis
Brief summary
This is a multi-center, randomized, two-part (Part A and Part B) study investigating the safety and efficacy of efimosfermin alfa in adult participants with compensated cirrhosis due to MASH. Participants who complete the treatment during Part A of the study and meet the inclusion criteria will have the option to enroll in Part B (open label) of the study.
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
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The Part A of study 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 enrolment. * Participants with history or presence of at least two components of metabolic syndrome. * Liver biopsy consistent with cirrhosis (fibrosis stage 4).
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 mellitus complications. * History or evidence of chronic pancreatic disease; pancreatic injury or acute pancreatitis within 6 months before Screening. * A recent history or planned surgical procedures or medications intended to produce significant weight loss. * Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) \>= 5 times upper limit normal (ULN). * Current or history of excessive alcohol intake
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Proportion of participants achieving improvement in liver fibrosis by >=1 stage and no worsening of MASH | At Week 96 | Participants experiencing improvement in liver fibrosis of \>=1 stage (based on MASH Clinical Research Network (CRN) fibrosis score) and no worsening of MASH (defined as no increase in nonalcoholic fatty liver disease activity score for ballooning, inflammation, or steatosis). MASH CRN fibrosis score ranges from 0 to 4, higher score indicates greater severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Proportion of participants achieving change from Baseline in vibration-controlled transient elastography (VCTE)- liver stiffness measurement (LSM) and in enhanced liver fibrosis (ELF) score | Baseline (Day 1) and Week 96 | 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. |
| Part A Change from Baseline in VCTE-LSM | Baseline (Day 1) and Week 96 | VCTE-LSM is a non-invasive test that uses vibration-controlled transient elastography to measure the stiffness of the liver in kPa. |
| Part A: Proportion of participants with Treatment-Emergent Adverse Events (TEAEs) and TEAEs by severity | Week 96 | — |
| Part A: Proportion of participants with TEAEs leading to discontinuation and TEAEs leading to discontinuation by severity | Week 96 | — |
| Part A: Proportion of participants with Grade 3 and Grade 4 laboratory abnormalities | Week 96 | — |
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