Health Condition 1: K74- Fibrosis and cirrhosis of liver
Conditions
Interventions
Intervention1: Efruxifermin (EFX) 50 mg: Efruxifermin is a fusion protein, comprised of human IgG1Fc linked
to modified human Fibroblast Growth Factor 21 (FGF21).
Efruxifermin will be administered sub
Sponsors
Ms Klinera Global Services
Eligibility
Inclusion criteria
Inclusion criteria: 1.Males and non-pregnant, non-lactating females between 18–75 years of age, inclusive, on the day of signing informed consent. 2.Previous history or presence of T2D (as determined by medical history or based on screening lab values if previously undiagnosed [i.e. HbA1c greater than or equal to 6.5%]) or 2 out of 4 components of metabolic syndrome (obesity, dyslipidemia, elevated blood pressure, elevated fasting glucose). 3.Body-mass index (BMI) greater than or equal to 25.0 kg/m2 4.Suspected or confirmed diagnosis of NASH/NAFLD or non-invasively diagnosed NASH/NAFLD, identified based on ONE of the following: a. Recent liver biopsy (obtained within 365 days prior to screening) documenting definite NASH or presumed NASH with evidence of metabolic disease and no other etiology for liver disease b.Recent median liver fat greater than or equal to 8.0% as assessed by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) Note: Historical MRI-PDFF must have been obtained within 180 days prior to Screening, unless subject consented to the Optional MRI-PDFF/cT1 substudy c.Recent Corrected T1 (cT1) greater than or equal to 840 ms as assessed by LiverMultiScan® Note: Historical cT1 must have been obtained within 180 days prior to Screening, unless subject consented to the Optional MRI-PDFF/cT1 substudy d.FibroScan® liver stiffness measurement (LSM) greater than or equal to 7.5 kilopascals (kPa) AND Controlled Attenuation Parameter (CAP) greater than or equal to 280 dB.m-1 at Screening e.ELF score greater than or equal to 7.7 Note: If a historical value for an ELF test performed less than or equal to 90 days prior to the Screening visit is available, then the screening ELF score does not need to be repeated f. Recent mean liver stiffness greater than or equal to 2.5 kPa as assessed by magnetic resonance elastography (MRE) Note: Historical MRE must have been obtained within 180 days prior to Screening 5.Central laboratory tests at screening that meet all of the following criteria: a.Estimated glomerular filtration rate (eGFR) greater than or equal to 15 mL/min, as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI); b.HbA1c less than or equal to 9.5%; c.International Normalized Ratio (INR) d.Total bilirubin e.Creatine kinase (CK) f.Platelet count greater than or equal to 100,000/µL; g.Triglyceride (TG) level less than or equal to 500 mg/dL; h.Aspartate aminotransferase (AST) > 17 for females and > 20 for males, AST less than or equal to 5 × ULN; i. Alanine aminotransferase (ALT) less than or equal to 5 × ULN; j.Alkaline phosphatase (ALP) k.25-Hydroxy Vitamin D greater than or equal to 20 ng/mL Note: Laboratory tests for eligibility assessment may be repeated one time at the Investigator’s discretion 6.Documented stability of ALT and AST levels, as evidenced by no significant worsening of ALT and AST values at pre-baseline relative to screening values and the following parameters: a. If the screening and pre-b
Exclusion criteria
Exclusion criteria: 1.Weight loss > 10% in the 90 days prior to screening 2.Type 1 diabetes 3.Unstable T2D defined as: a.Insulin dose adjustment > 35% within 30 days prior to screening through randomization, b.Any prior history of diabetic ketoacidosis and/or hyperglycemic hyperosmolar state 4.Hypoglycemia unawareness, hospitalization due to hypoglycemia, or history of severe hypoglycemia (hypoglycemia requiring outside assistance to regain normal neurologic status) within 90 days prior to screening 5.Subjects with osteoporosis, defined as a T-score of less than or equal to minus 2.5 at the femoral neck, total hip, or lumbar spine based on a centrally read dual-energy X-ray absorptiometry (DXA) scan performed during screening Note: A historical DXA scan performed within 90 days prior to screening may be accepted as the screening DXA scan. The historical scan must have been performed on a scanner previously qualified by the central imaging vendor that is available for use at post-baseline visits 6.Poorly controlled hypertension (systolic blood pressure > 160 mm Hg, or diastolic blood pressure > 100 mm Hg) at the Screening visit or Pre-Baseline visit Note: Vital signs for eligibility assessment may be repeated one time at the Investigator’s discretion 7.Any current or prior history of decompensated liver disease including ascites requiring medical management, hepatic encephalopathy (HE), or variceal bleeding 8.Model for End-Stage Liver Disease (MELD) score > 12, unless due to therapeutic anticoagulation or Gilbert’s syndrome 9.Child-Pugh score > 6 (Class B or C), unless due to therapeutic anticoagulation or Gilbert’s syndrome 10.History of pancreatitis 11.Chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen [HBsAg] positive) or acute hepatitis A infection (hepatitis A immunoglobulin M [IgM] antibody positive). For subjects with positive hepatitis B core antibody (HBcAb), HBV deoxyribonucleic acid (DNA) by quantitative polymerase chain reaction (PCR) will be required 12.Chronic hepatitis C virus (HCV) infection (HCV antibody [Ab] and HCV ribonucleic acid [RNA] positive). Subjects cured of HCV infection less than 2 years prior to the Screening visit (based on date of RNA PCR negative confirmation following conclusion of treatment) are not eligible 13.Prior (less than 2 years prior to screening) or planned (during the study period) bariatric surgery (e.g., gastroplasty, Roux-en-Y gastric bypass) or reversal or removal of intragastric balloon. Surgery failure less than 2 years prior to screening is also exclusionary 14.Other causes of liver disease based on medical history and/or liver histology and/or central laboratory results, including but not limited to: alcoholic liver disease, autoimmune disorders (e.g., primary biliary cholangitis [PBC], primary sclerosing cholangitis [PSC], autoimmune hepatitis), drug induced hepatotoxicity, Wilson disease, or clinically significant iron overload 15.History of liver transplantation 16.Current or prior history of hepatocellular carcinoma (HCC) 17.Current diagnosis of Cushing’s syndrome 18.History of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to screening Note: Significant alcohol consumption is defined as an average exceeding 1 ethanol containing drink/day in female subjec
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety & tolerability will be assessed through the reporting of extent of exposure, AEs, and clinical assessmentsTimepoint: 52 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in FAST Score • Change from baseline in ELF score and components (TIMP-1, HA, PIIINP), Pro-C3, and liver stiffness assessed by FibroScan®Timepoint: 52 Weeks | — |
Countries
Argentina, Australia, Canada, France, Germany, India, Israel, Italy, Malaysia, Mexico, Poland, Republic of Korea, Spain, Switzerland, Taiwan, Turkey, United Kingdom, United States of America
Contacts
Public ContactRajeev Singh
Klinera Global Services
Outcome results
None listed