A Study of Pemafibrate in Patients With Nonalcoholic Fatty Liver Disease (NAFLD)

Study Overview
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Brief Summary
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Pemafibrate in Patients With Nonalcoholic Fatty Liver Disease.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Pemafibrate in Patients With Nonalcoholic Fatty Liver Disease.

Conditions
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Non-Alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: K-877
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients show presence of hepatic fat fraction as defined by ≥ 10% on MRI-PDFF at Screening Patients show presence of liver stiffness as defined by ≥ 2.5 kPa on MRE at Screening Patients have an ALT above the upper limits of normal (30 IU/L for females and 40 IU/L for males) at Screening Patients with NAFLD had to be age 20 years or older at written informed consent(ICF) Exclusion Criteria: Current of significant alcohol consumption (significant alcohol consumption is defined as more than 210 g/week in males and more than 140 g/week in females, on average) Planned use of Contraindicated Medications from written ICF to end of treatment. BMI < 22 kg/m2 at Screening Uncontrolled diabetes mellitus as defined by a HbA1c(NGSP) ≥ 8.0％ at Screening eGFR < 30 mL/min/1.73m2 or Dialysis patient Cirrhosis Biliary obstruction Patients were excluded if they had evidence of other forms of liver disease shown by the following: Hepatitis B or Hepatitis C Autoimmune hepatitis（AIH） Primary biliary cirrhosis（PBC） Primary Sclerosing Cholangitis（PSC） Drug-induced liver injury hyperthyroidism, Wilson's disease, hemochromatosis, alpha-1-antitrypsin disease Those with complicating malignant neoplasm or those judged to be at a high risk of recurrence Patients with contraindications to MRI imaging Patients who gave 200 mL or more of blood within 1 month before the administration of the study drug, or 400 mL or more of blood within 4 months before the administration of the study drug Patients with a history of serious drug allergies (such as anaphylactic shock) Pregnancy, breast feeding, planned pregnancy Patients who were participating in another clinical study at the time of consent was obtained or who received study drugs other than the placebo less than 16 weeks before consent was obtained Patients who have previously been administered pemafibrate Patients who have been determined inappropriate by the investigator or subinvestigator

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group<br>K-877 (pemafibrate) tablet twice daily. | Drug: K-877<br>* 0.2mg tablet<br>* Other names: pemafibrate;|
| Placebo Comparator: Control Group<br>placebo tablet twice daily. | Drug: Placebo<br>* K-877 matching placebo tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: % Change from baseline to Week 24 in hepatic fat fraction by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF) |  | Week 24 | 
| Safety: Incidence of adverse events and adverse drug reactions that occurred after the administration of the study drug |  | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in noninvasive imaging biomarkers (MRI-PDFF in %, MRE in kPa, Transient elastography in kPa) |  | From baseline upto week 72 | 
| Change in clinical laboratory tests (AST in IU/L, ALT in IU/L, γ-GTP in IU/L) |  | From baseline upto week 72 | 
| Change in noninvasive biomarkers (Cytokeratin 18 in U/L, Hyaluronic acid in ng/mL, Type IV collagen 7S in ng/mL, M2BPGi in no unit) |  | From baseline upto week 72 | 
| Change in noninvasive biomarkers (NAFLD fibrosis score) |  | From baseline upto week 72 | 
| Change in noninvasive biomarkers (FIB4 index) |  | From baseline upto week 72 | 
| Change in noninvasive biomarkers (NAFIC score) |  | From baseline upto week 72 | 
| Change in noninvasive biomarkers (ELF test) |  | From baseline upto week 72 | 
| Percentage of patients with ≥ 30% reduction in hepatic fat fraction (MRI-PDFF) |  | From baseline upto week 72 | 
| Percentage of patients with ≥ 15% reduction in liver stiffness (MRE) |  | From baseline upto week 72 |