Health Condition 1: K758- Other specified inflammatory liverdiseases
Conditions
Interventions
Intervention1: Efruxifermin (EFX) 28mg Efruxifermin (EFX) 50 mg: Efruxifermin is a fusion protein, comprised of human IgG1Fc linked to modified, human Fibroblast Growth Factor 21 (FGF21). Efruxifermin
Sponsors
Akero Therapeutics, Inc.
KlinEra Global Services
Eligibility
Inclusion criteria
Inclusion criteria: 1. Males and non-pregnant, non-lactating females between 18ââ?¬â??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. Subjects who do not have a historical liver biopsy specimen that meets Inclusion Criteria 7 must meet either inclusion criterion 4a OR 4b prior to collection of a liver biopsy specimen during the Screening visit: a. FibroScanÃ?® liver stiffness measurement (LSM) > 7.5 kPa, OR b. Enhanced Liver Fibrosis (ELF) score greater than or equal to 7.7 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. Hemoglobin A1c (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/Ã?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 Ã?â?? ULN; i. Alanine aminotransferase (ALT) less than or equal to 5 Ã?â?? 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 Investigatorââ?¬•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-baseline ALT and AST values are both less than or equal to 1.5 Ã?â?? ULN, there is no limit to the difference between the values. b. If at least 1 of the screening or pre-baseline values of ALT or AST is > 1.5 Ã?â?? ULN and shows worsening at pre-baseline, the percent increase must be less than or equal to 50%. Note: Subjects must have ALT and AST repeated during the screening period (Pre-Baseline visit) at minimum 28 days between blood draws to confirm either criterion 6a or 6b above. Laboratory tests for eligibility assessment may be repeated one time at the Investigatorââ?¬•s discretion. 7. Biopsy-proven NASH. Must have had a liver biopsy obtained less than or equal to 180 days prior to screening with fibrosis stage 1, 2, or 3 and a non-alcoholic fatty liver disease (NAFLD) activity score (NAS) of more than or equal to 4 with at least 1 point in each of the following components: a. Steatosis (scored 0 to 3), b. Ballooning degeneration (scored 0 to 2), and c. Lobular inflammation (scored 0 to 3) Note: F1 subjects will be
Exclusion criteria
Exclusion criteria: 1.Presence of cirrhosis on liver biopsy (fibrosis stage 4). 2.Weight loss > 10% within 90 days prior to the collection date of the liver biopsy specimen used to assess subject eligibility. 3.Type 1 diabetes. 4.Unstable Type 2 diabetes 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. 5.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. 6.Subjects with osteoporosis, defined as a T-score of less than or equal to -2.5 at the femoral neck, total hip, or lumbar spine based on a centrally read 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. 7.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 Investigatorââ?¬•s discretion 8.Any current or prior history of decompensated liver disease including ascites requiring medical management, hepatic encephalopathy (HE), or variceal bleeding. 9.Model for End-Stage Liver Disease (MELD) score > 12, unless due to therapeutic anticoagulation or Gilbertââ?¬•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 DNA by quantitative polymerase chain reaction (PCR) will be required. 12.Chronic hepatitis C virus (HCV) infection (HCV antibody [Ab] and HCV 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 centralized review of 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 Cushingââ?¬•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 femal
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects with fibrosis stage 2 or 3 who achieve NASH resolution (defined as a NAS of 0ââ?¬â??1 for inflammation & 0 for ballooning) AND greater than or equal to 1 stage improvement in fibrosis (based on NASH CRN fibrosis score)Timepoint: Week52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects with fibrosis stage 2 or 3 who achieve NASH resolution (defined as a NAS of 0ââ?¬â??1 for inflammation & 0 for ballooning) & no worsening of fibrosis (based on NASH CRN fibrosis score) Proportion of subjects with fibrosis stage 2 or 3 who achieve greater than or equal to 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) & no worsening of steatohepatitis (defined as no increase in NAS for ballooning, inflammation, or steatosis)Timepoint: Week 52 | — |
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