Health Condition 1: K758- Other specified inflammatory liverdiseases
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).
EFX will be provided as a lyophil
Sponsors
Akero Therapeutics, Inc.
Klinera Global Services
Eligibility
Inclusion criteria
Inclusion criteria: 1.Males and non-pregnant, non-lactating females between 18â??80 years of age, inclusive, on the day of signing informed consent.2.Previous history or presence of type 2 diabetes (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.Cohort 1 Subjects only: Subjects who do not have a historical liver biopsy specimen (meeting Inclusion Criteria 5 below) must meet either inclusion criterion 4a OR 4b: a. FibroScan liver stiffness measurement (LSM) greater than or equal to 15 kilopascals (kPa) Note: All subjects must complete a FibroScan examination during the screening period, unless historical values for a FibroScan assessment performed within 12 weeks prior to baseline/Day 1 (or up to 14 weeks prior to baseline/Day 1 with an approved screening window extension) are available.b. ELF score greater than or equal to 9.8.5.Cohort 1 Subjects only: Biopsy-proven compensated cirrhosis (fibrosis stage 4) due to NASH/MASH based on a centrally read biopsy. Must have had a liver biopsy obtained less than or equal to 365 days prior to screening with fibrosis stage 4 and a NAFLD activity score (NAS) of greater than or equal to 3 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) 6.Cohort 2 Subjects only: Subjects must meet either Inclusion Criterion 6a, 6b, OR 6c below:a.Biopsy-proven compensated cirrhosis (fibrosis stage 4) with no competing etiology for liver disease. Must have had a liver biopsy specimen collected during screening or within 365 days prior to screening with confirmation of fibrosis stage 4 from a pathologist (centrally or locally read).Note: A subject cannot be considered for Cohort 2 based on Inclusion Criterion 6b or 6c if a biopsy previously submitted for central read failed to meet Inclusion Criterion 6a. If there is reason to suspect progression to cirrhosis, a new biopsy may be obtained and submitted for evaluation (centrally or locally) OR b.FibroScan LSM greater than or equal to 20.0 kPa. Note: All subjects must complete a FibroScan examination during the screening period, unless historical values for a FibroScan assessment performed within 12 weeks prior to baseline/Day 1 (or up to 14 weeks prior to baseline/Day 1 with an approved screening window extension) are available OR c.ELF score greater than or equal to 10.5.7.Central laboratory tests that meet all of the following criteria at screening: a.Albumin greater than or equal to 3.5 g/dL.b.Estimated glomerular filtration rate (eGFR) greater than or equal to 15 mL/min, as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI).c.Hemoglobin A1c (HbA1c) less than or equal to 9.5%.d.International Normalized Ratio (INR) less than or equal to 1.3, unless due to therapeutic anticoagulation.e.Direct bilirubin less than or equal to 0.5 mg/dL.f.Creatine kinase (CK) less than 3 Ã? upper limit of normal (ULN). g.Triglyceride (TG) level less than or equal to 500 mg/dL.h.25-Hydroxy Vitamin D greater than or equal to 13 ng/mL.Note: Laboratory tests for eligibility assessment may be repeated one time at the Investigatorâ??s discretion. A subject who fails to meet Inclusion Cri
Exclusion criteria
Exclusion criteria: 1.Weight loss at screening defined as: a. Cohort 1: Weight loss greater than 10% within 90 days prior to the collection date of the liver biopsy specimen used to assess subject eligibility through randomization.b.Cohort 2: Weight loss greater than 10 % within 90 days prior to screening through randomization.2. Type 1 diabetes.3.Unstable T2D defined as: a.Insulin dose adjustment greater than 35% within 30 days prior to screening through randomization. b. Any prior history of diabetic ketoacidosis and/or hyperosmolar hyperglycemic 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 greater than 160 mm Hg, or diastolic blood pressure greater than 100 mm Hg) at the Screening visit or Pre-baseline visit. Note: Vital signs for eligibility assessment may be repeated one time at the Investigatorâ??s discretion.7.Presence of varices (Cohort 1) OR presence of high-risk varices (Cohort 2), based on a centrally read upper gastrointestinal (GI) EGD exam conducted at screening.8.Any current or prior history of decompensated liver disease including ascites, hepatic encephalopathy (HE), or variceal bleeding.9.Model for End-Stage Liver Disease (MELD) score greater than 12, unless due to hemolytic anemia, therapeutic anticoagulation, or Gilbertâ??s syndrome.10.Child-Pugh score greater than 6 (Class B or C), unless due to hemolytic anemia, therapeutic anticoagulation, or Gilbertâ??s syndrome.11.History of significant pancreatic disorders (acute pancreatitis, chronic pancreatitis, hereditary pancreatitis, and pancreatic cancer). 12.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.13.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.Note: Subjects who were previously diagnosed with chronic HCV infection who achieved sustained viral response (SVR) following treatment, or subjects with spontaneous clearance of HCV infection (positive serology for HCV infection, negative for HCV RNA at screening, and no documented history of acute HCV infection within 2 years prior to screening) may be enrolled.14. 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 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of subjects who achieve more than or equal to 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) and no worsening of steatohepatitis (defined as no increase in NAS for ballooning, inflammation, or steatosis) at Week 96 (Cohort 1 only).Timepoint: Week 96 | — |
Secondary
| Measure | Time frame |
|---|---|
| Proportion of subjects who achieve more 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) at End of Study(Cohort 1) Proportion of subjects who achieve more than or equal to 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) at Week 96 & End of Study(Cohort 1) Proportion of subjects who achieve NASH/MASH resolution (defined as a NAS of 0â??1 for inflammation & 0 for ballooning) as determined by the NASH CRN criteria at Week 96 & End of Study.(Cohort 1) Proportion of subjects who achieve NASH/MASH resolution (defined as a NAS of 0â??1 for inflammation & 0 for ballooning) AND more than or equal to 1 stage improvement in fibrosis (based on NASH CRN fibrosis score) at Week 96 & End of Study(Cohort 1)Timepoint: Week 96 & End of Study;Change from baseline in ELF score & components (TIMP-1, HA, PIIINP), Pro-C3, liver stiffness assessed by FibroScan, & FAST score Change from baseline in ALT & AST Change from baseline in total cholesterol, TG, HDL-C, non-HDL-C, & LDL-C Change from baseline in HbA1c, C-peptide, adiponectin, insulin, & HOMA-IR Change from baseline in body weight Safety & tolerability will be assessed through the reporting of extent of exposure,AEs,and clinical assessmentsTimepoint: NA | — |
Countries
Argentina, Australia, Brazil, Canada, Chile, France, Germany, India, Israel, Italy, Mexico, Poland, Spain, Switzerland, Turkey, United Kingdom, United States of America
Contacts
Public ContactRajeev Singh
KlinEra Global Services
Outcome results
None listed