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

• ClinicalTrials.gov Identifier: NCT03350165
• Recruitment Status: Completed
• First Posted: November 22, 2017
• Last Update Posted: April 9, 2021
• Sponsor: Kowa Company, Ltd.
• Information provided by (Responsible Party): Kowa Company, Ltd.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non-Alcoholic Fatty Liver Disease	Drug: K-877; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 118 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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.
• Actual Study Start Date: December 27, 2017
• Actual Primary Completion Date: April 3, 2019
• Actual Study Completion Date: June 30, 2020

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Change in noninvasive imaging biomarkers (MRI-PDFF in %, MRE in kPa, Transient elastography in kPa) [ Time Frame: From baseline upto week 72 ]
2. Change in clinical laboratory tests (AST in IU/L, ALT in IU/L, γ-GTP in IU/L) [ Time Frame: From baseline upto week 72 ]
3. 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) [ Time Frame: From baseline upto week 72 ]
4. Change in noninvasive biomarkers (NAFLD fibrosis score) [ Time Frame: From baseline upto week 72 ]
5. Change in noninvasive biomarkers (FIB4 index) [ Time Frame: From baseline upto week 72 ]
6. Change in noninvasive biomarkers (NAFIC score) [ Time Frame: From baseline upto week 72 ]
7. Change in noninvasive biomarkers (ELF test) [ Time Frame: From baseline upto week 72 ]
8. Percentage of patients with ≥ 30% reduction in hepatic fat fraction (MRI-PDFF) [ Time Frame: From baseline upto week 72 ]
9. Percentage of patients with ≥ 15% reduction in liver stiffness (MRE) [ Time Frame: From baseline upto week 72 ]

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Japan

Aomori Prefectural Central Hospital

Aomori, Aomori, Japan, 030-8553

Asahikawa Medical University

Asahikawa, Hokkaido, Japan, 078-8510

Fukuwa Clinic

Chuo-ku, Tokyo, Japan, 104-0031

Fukuoka University Hospital

Fukuoka, Fukuoka, Japan, 814-0180

SeireiHamamatsu General Hospital

Hamamatsu, Shizuoka, Japan, 430-8558

Hamamatsu University Hospital

Hamamatsu, Shizuoka, Japan, 431-3192

Iwata City Hospital

Iwata, Shizuoka, Japan, 438-8550

Chutoen General Medical Center

Kakegawa, Shizuoka, Japan, 436-8555

Kurume University Hospital

Kurume, Fukuoka, Japan, 830-0011

Niigata University Medical & Dental Hospital

Niigata, Niigata, Japan, 951-8520

Ogaki Municipal Hospital

Ogaki, Gifu, Japan, 503-8502

Shiga University of Medical Science Hospital

Otsu, Shiga, Japan, 520-2192

Hokkaido University Hospital

Sapporo, Hokkaido, Japan, 060-8648

Yamagata University Hospital

Yamagata, Yamagata, Japan, 990-9585

Saiseikai Yokohamashi Tobu Hospital

Yokohama, Kanagawa, Japan, 230-8765

Yokohama City University Hospital

Yokohama, Kanagawa, Japan, 236-0004

Sponsors and Collaborators

Kowa Company, Ltd.

Investigators

• Study Director: Ryohei Tanigawa; Clinical Development Dept. Ⅰ

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Kowa Company, Ltd.
• ClinicalTrials.gov Identifier: NCT03350165
• Other Study ID Numbers: K-877-FL-01
• First Posted: November 22, 2017
• Last Update Posted: April 9, 2021
• Last Verified: April 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Digestive System Diseases