Health Condition 1: K758- Other specified inflammatory liverdiseases
Conditions
Interventions
Intervention1: Efimosfermin Alfa: Strength: 150 mg powder for solution for injection
Route: Subcutaneous
Frequency: Once Every 4 weeks
Duration: 52 weeks
Control Intervention1: Placebo: Strength: P
Sponsors
GSK Research & Development Limited
IQVIA RDS India Private Limited
Eligibility
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 is more than 18 years and less than 75 years at enrollment. 3.History or presence of 2 or more of the 5 components of metabolic syndrome per American Heart Association definition. a. Obesity/overweight (BMI more than or equal to 25 kg/m2; BMI more than or equal to 23 kg/m2 for Asian regions) or waist circumference of more than or equal to 40 inches (102 cm) for men and more than or equal to 35 inches (89 cm) for women b. Increased triglycerides: more than or equal to 150 mg/dL (1.7 mmol/L) or taking medications to lower triglycerides c. Reduced HDL cholesterol: males, less than or equal to1.03 mmol/L (40 mg/dL); females, less than or equal to 1.29 mmol/L (50 mg/dL) d. Elevated fasting glucose (more than or equal to 100 mg/dL; more than or equal to 5.6 mmol/L), or on drug treatment for elevated glucose e. Hypertension 4. History or presence of at least 1 of the 3 components of known or suspected MASH: a. Enhanced liver fibrosis (ELF) scores more than or equal to 7.7 and less than or equal to 11.3 within 3 months prior to randomization b. VCTE-LSM more than or equal to 8.0 and less than 20 kPa within 3 months prior to Randomization c. A liver biopsy consistent with suspected MASH, showing at least 1 point for each NAS component and evidence of fibrosis. 5. Stable body weight for the past 6 months (change less than or equal to 5%). 6. Females are eligible to participate if they are not pregnant or breast feeding, and one of the following conditions applies: a. Not a participant of childbearing potential (POCBP) as defined in Section 10.5.1., or b. A POCBP who agrees to follow the contraceptive guidance during the treatment period and for more than or equal to 16 weeks after the last dose of study drug.
Exclusion criteria
Exclusion criteria: 1. Vitamin D less than or equal to 12 ng/mL. Individuals with values more than 12 ng/mL but less than 20ng/mL should agree to receive vitamin D supplementation according to the standard of care or local guidelines to ensure rapid repletion. 2. ALT or AST more than or equal to 5 upper limit of normal (ULN) 3. Total bilirubin more than or equal to 1.3 mg/dL. Individuals with documented Gilbert s syndrome may be enrolled if they experienced an isolated increase in total bilirubin of more than or equal to 1.3 mg/dL and direct bilirubin is less than or equal to 20% of total bilirubin; otherwise, the individual will be excluded. 4. Serum albumin less than or equal to 3.5 g/dL. 5. International normalized ratio (INR) more than or equal to 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. 6. Alkaline phosphatase (ALP) more than or equal to 2 ULN 7. Hemoglobin (Hb) less than or equal to 11.0 g/dL for males and less than or equal to 10.0 g/dL for females 8. Neutrophils less than or equal to 1500/mm3 (Black participants: less than or equal to 1200/mm3); individuals with documented benign ethnic neutropenia may be enrolled at the discretion of the Study Medical Monitor. 9. Platelet (PLT) count less than 140,000/mm3; individuals with a PLT count between 110,000/mm3 and 140,000/mm3 may be enrolled after discussion with the Study Medical Monitor. 10. Serum creatinine more than or equal to 1.5 mg/dL or creatinine clearance less than or equal to 60 mL/min/1.73 m2 by Chronic Kidney Disease Epidemiology Collaboration equation (2021). 11. Alpha-fetoprotein more than or equal to 20 ng/mL 12. Thyroid stimulating hormone outside the normal reference range unless free thyroxine value is within the normal range 13. Triglycerides more than or equal to 500 mg/dL 14. HbA1c more than or equal to 9.0% 15. MELD 3.0 score more than or equal to 12 unless the score is elevated in the absence of liver dysfunction (eg, Gilbert s syndrome) 16. Phosphatidylethanol (PEth) more than or equal to 80 ng/mL at Screening 17. 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) 18.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. 19. Current or chronic history of biliary disease (including symptomatic or complicated cholelithiasis), or a history of acute cholecystitis, biliary surgery or intervention, within the previous 6 months. 20. History or evidence of pancreatic disease, including pancreatitis.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the effects of efimosfermin on safety and tolerability.Timepoint: 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 |
|---|---|
| To assess the effects of efimosfermin on ELF score.Timepoint: Week 52;To assess the effects of efimosfermin on VCTE-LSM score.Timepoint: Week 52;To assess the effects of efimosfermin on MRE score.Timepoint: Week 52 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, France, Germany, Greece, Hong Kong, India, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Poland, Republic of Korea, Saudi Arabia, Singapore, Spain, Taiwan, Turkey, United Kingdom, United States of America
Contacts
Public ContactShweta Pradhan
IQVIA RDS (India) Private Limited
Outcome results
None listed