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

Phase 2

Completed

• Conditions: Non-Alcoholic Fatty Liver Disease
• Interventions: Drug: Placebo; Drug: K-877

• Registration Number: NCT03350165
• Lead Sponsor: Kowa Company, Ltd.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-11-09
• Study First Submitted QC: 2017-11-20
• Study First Posted: 2017-11-22
• Study Start: 2017-12-27
• Primary Completion: 2019-04-03
• Study Completion: 2020-06-30
• Status Verified: 2021-04
• Last Update Submitted: 2021-04-08
• Last Update Posted: 2021-04-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 118

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Group	Placebo	placebo tablet twice daily.
Treatment Group	K-877	K-877 (pemafibrate) tablet twice daily.

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Percentage of patients with ≥ 15% reduction in liver stiffness (MRE)	From baseline upto week 72
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

Trial Locations

Locations (16)

Fukuwa Clinic; 🇯🇵 Chuo-ku, Tokyo, Japan

Fukuoka University Hospital; 🇯🇵 Fukuoka, Fukuoka, Japan

Niigata University Medical & Dental Hospital; 🇯🇵 Niigata, Niigata, Japan

Hamamatsu University Hospital; 🇯🇵 Hamamatsu, Shizuoka, Japan

Kurume University Hospital; 🇯🇵 Kurume, Fukuoka, Japan

Shiga University of Medical Science Hospital; 🇯🇵 Otsu, Shiga, Japan

Yamagata University Hospital; 🇯🇵 Yamagata, Yamagata, Japan

Aomori Prefectural Central Hospital; 🇯🇵 Aomori, Aomori, Japan

Iwata City Hospital; 🇯🇵 Iwata, Shizuoka, Japan

Chutoen General Medical Center; 🇯🇵 Kakegawa, Shizuoka, Japan

Hokkaido University Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Saiseikai Yokohamashi Tobu Hospital; 🇯🇵 Yokohama, Kanagawa, Japan

Yokohama City University Hospital; 🇯🇵 Yokohama, Kanagawa, Japan

Asahikawa Medical University; 🇯🇵 Asahikawa, Hokkaido, Japan

SeireiHamamatsu General Hospital; 🇯🇵 Hamamatsu, Shizuoka, Japan

Ogaki Municipal Hospital; 🇯🇵 Ogaki, Gifu, Japan