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

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.

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.

Study Overview

• Status: Completed
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: K-877; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 118
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Aomori, Aomori, Japan, 030-8553
    • Aomori Prefectural Central Hospital
  • Asahikawa, Hokkaido, Japan, 078-8510
    • Asahikawa Medical University
  • Chuo-ku, Tokyo, Japan, 104-0031
    • Fukuwa Clinic
  • Fukuoka, Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Hamamatsu, Shizuoka, Japan, 430-8558
    • SeireiHamamatsu General Hospital
  • Hamamatsu, Shizuoka, Japan, 431-3192
    • Hamamatsu University Hospital
  • Iwata, Shizuoka, Japan, 438-8550
    • Iwata City Hospital
  • Kakegawa, Shizuoka, Japan, 436-8555
    • Chutoen General Medical Center
  • Kurume, Fukuoka, Japan, 830-0011
    • Kurume University Hospital
  • Niigata, Niigata, Japan, 951-8520
    • Niigata University Medical & Dental Hospital
  • Ogaki, Gifu, Japan, 503-8502
    • Ogaki Municipal Hospital
  • Otsu, Shiga, Japan, 520-2192
    • Shiga University of Medical Science Hospital
  • Sapporo, Hokkaido, Japan, 060-8648
    • Hokkaido University Hospital
  • Yamagata, Yamagata, Japan, 990-9585
    • Yamagata University Hospital
  • Yokohama, Kanagawa, Japan, 230-8765
    • Saiseikai Yokohamashi Tobu Hospital
  • Yokohama, Kanagawa, Japan, 236-0004
    • Yokohama City University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients show presence of hepatic fat fraction as defined by ≥ 10% on MRI-PDFF at Screening
2. Patients show presence of liver stiffness as defined by ≥ 2.5 kPa on MRE at Screening
3. Patients have an ALT above the upper limits of normal (30 IU/L for females and 40 IU/L for males) at Screening
4. Patients with NAFLD had to be age 20 years or older at written informed consent(ICF)

Exclusion Criteria:

1. 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)
2. Planned use of Contraindicated Medications from written ICF to end of treatment.
3. BMI < 22 kg/m2 at Screening
4. Uncontrolled diabetes mellitus as defined by a HbA1c(NGSP) ≥ 8.0％ at Screening
5. eGFR < 30 mL/min/1.73m2 or Dialysis patient
6. Cirrhosis
7. Biliary obstruction

8. 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
9. Those with complicating malignant neoplasm or those judged to be at a high risk of recurrence
10. Patients with contraindications to MRI imaging
11. 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
12. Patients with a history of serious drug allergies (such as anaphylactic shock)
13. Pregnancy, breast feeding, planned pregnancy
14. 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
15. Patients who have previously been administered pemafibrate
16. Patients who have been determined inappropriate by the investigator or subinvestigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Kowa Company, Ltd.
• Investigators: Study Director: Ryohei Tanigawa, Clinical Development Dept. Ⅰ

Publications and helpful links

General Publications

• Nakajima A, Eguchi Y, Yoneda M, Imajo K, Tamaki N, Suganami H, Nojima T, Tanigawa R, Iizuka M, Iida Y, Loomba R. Randomised clinical trial: Pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator (SPPARMalpha), versus placebo in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2021 Nov;54(10):1263-1277. doi: 10.1111/apt.16596. Epub 2021 Sep 16.
• Fruchart JC, Hermans MP, Fruchart-Najib J, Kodama T. Selective Peroxisome Proliferator-Activated Receptor Alpha Modulators (SPPARMalpha) in the Metabolic Syndrome: Is Pemafibrate Light at the End of the Tunnel? Curr Atheroscler Rep. 2021 Jan 3;23(1):3. doi: 10.1007/s11883-020-00897-x.

Study record dates

Study Major Dates

• Study Start (Actual): December 27, 2017
• Primary Completion (Actual): April 3, 2019
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: November 9, 2017
• First Submitted That Met QC Criteria: November 20, 2017
• First Posted (Actual): November 22, 2017

Study Record Updates

• Last Update Posted (Actual): April 9, 2021
• Last Update Submitted That Met QC Criteria: April 8, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: K-877-FL-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No