Non-cirrhotic metabolic dysfunction-associated steatohepatitis
Conditions
Interventions
Participants will be enrolled and randomized to receive efimosfermin dose level 1, efimosfermin dose level 2, or placebo for a period of 52 weeks.
Sponsors
Lochhead Paul
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Able and willing to understand and sign a written ICF that must be obtained prior to the initiation of study procedures 2. Age >- 18 and <- 75 years at enrollment 3. History or presence of 2 or more of the 5 components of metabolic syndrome per American Heart Association definition 4. History or presence of known or suspected MASH
Exclusion criteria
Exclusion criteria: 1. ALT or AST >- 5 X upper limit of normal (ULN) 2. Total bilirubin >- 1.3 mg/dL. Individuals with documented Gilbert's syndrome may be enrolled if they experienced an isolated increase in total bilirubin of >- 1.3 mg/dL and direct bilirubin is - 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. 5. Alkaline phosphatase (ALP) >- 2 X ULN 6. Platelet (PLT) count - 1.5 mg/dL or creatinine clearance - 9.0% 9. MELD 3.0 score >- 12 unless the score is elevated in the absence of liver dysfunction (eg, Gilbert's syndrome) 10. Phosphatidylethanol (PEth) >- 80 ng/mL at Screening 11. Evidence of infection with any of the following: a. Human immunodeficiency virus b. Hepatitis B virus (detectable HBsAg at Screening) c. Hepatitis C virus (HCV) 12. 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. 13. Current or history of excessive alcohol intake for >- 3 months within the 12-month period prior to Screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| For all participants at Week 52, - Incidence and severity of TEAEs. - Incidence and severity of TEAEs leading to discontinuation. - Incidence of Grade 3 and Grade 4 laboratory abnormalities. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Absolute and relative change from baseline to Week 52 in ELF score for all participants. - Achieving an improvement in ELF score of >- 0.5. - Absolute and relative change from baseline to Week 52 in VCTE-LSM scores for all participants. - Achieving a change from baseline in VCTE-LSM >- 30% at Week 52. - Absolute and relative change from baseline to Week 52 in the subset of participants with MRE scores. - Absolute and relative change from baseline to Week 52 in HFF by MRI-PDFF for all participants. - Absolute and relative change from baseline to Week 52 in ALT, AST, and ALT/AST ratio for all participants. - Achieving ALT and HFF normalization at Week 52. - Achieving HFF <- 5% at Week 52. - Change from baseline to Week 52 in HbA1c for participants with T2DM. - Change from baseline to Week 52 in body weight for all participants. - Change from baseline in fasting total cholesterol, LDL-C, HDL-C, and fasting triglycerides at Week 52 for all participants. - Incidence of ADAs at Week 52. - Efimosfermin serum concentrations in participants with PK data following multiple doses. | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, France, Germany, Greece, Hong Kong, India, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Poland, Saudi Arabia, Singapore, South Korea, Spain, Taiwan, Turkiye, United Kingdom, United States
Contacts
Public ContactPaul Lochhead
GlaxoSmithKline K.K.
Outcome results
None listed