Health Condition 1: K758- Other specified inflammatory liverdiseases
Conditions
Interventions
Intervention1: Efimosfermin Alfa: Strength: 150 mg powder for solution for injection
Route: Subcutaneous
Control Intervention1: Placebo: Strength: Powder for solution for injection
Route: Subcutaneou
Sponsors
GSK Research & Development 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. Magnetic resonance imaging (MRI)-derived proton density fat fraction (PDFF) more than or equal to 8% for new or historical analysis submitted to the central reader less than or equal to 3 months before randomization. 4. Stable body weight for the past 6 months (change less than or equal to 5%). 5. Liver biopsy confirmation of MASH consistent with stage F2 or F3 fibrosis and a NAS score more than or equal to 4 confirmed by a central pathologist a. If a historical liver biopsy was performed less than or equal to 6 months before Screening, the individual may proceed with Screening if the following conditions are confirmed: i. The biopsy has been reviewed by a central pathologist and is consistent with the inclusion criteria. ii. No concomitant investigational drugs are being received. b. If a historical liver biopsy is unavailable, a liver biopsy can be performed at Screening if the following conditions are met: i. The individual must meet all other inclusion-exclusion criteria for the study. ii. FibroScan-AST (FAST) value more than or equal to 0.35. 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. Contraindication or ineligibility for percutaneous liver biopsy Laboratory and Imaging Findings. 2. 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. 3. ALT or AST more than or equal to 5 upper limit of normal (ULN) 4. 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. 5. Serum albumin less than or equal to 3.5 g/dL. 6. 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. 7. Alkaline phosphatase (ALP) more than or equal to 2 ULN 8. 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 9. 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. 10. 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. 11. 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). 12. Alpha-fetoprotein more than or equal to 20 ng/mL 13. Thyroid stimulating hormone outside the normal reference range unless free thyroxine value is within the normal range 14. Triglycerides more than or equal to 500 mg/dL 15. HbA1c more than or equal to 9.0%
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To determine the effect of 225 mg and 300 mg efimosfermin compared to placebo on histologic resolution of MASH and improvement in fibrosis after 52 weeks of Q4W SC injections. Timepoint: Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the effects of efimosfermin on safety and tolerabilityTimepoint: Week 52 and Month 48 | — |
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