Clinical trial NCT03350165: A Study of Pemafibrate in Patients With Nonalcoholic Fatty Liver Disease (NAFLD)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Alcoholic Fatty Liver Disease
Lead sponsor: Kowa Company, Ltd.
Sponsor class: INDUSTRY
First posted: 2017-11-22
Enrollment: 118
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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

Primary outcomes:
measure: Efficacy: % Change from baseline to Week 24 in hepatic fat fraction by Magnetic Resonance Imaging - Proton Density Fat Fraction (MRI-PDFF)
timeFrame: Week 24
measure: Safety: Incidence of adverse events and adverse drug reactions that occurred after the administration of the study drug
timeFrame: Week 24
Secondary outcomes:
measure: Change in noninvasive imaging biomarkers (MRI-PDFF in %, MRE in kPa, Transient elastography in kPa)
timeFrame: From baseline upto week 72
measure: Change in clinical laboratory tests (AST in IU/L, ALT in IU/L, γ-GTP in IU/L)
timeFrame: From baseline upto week 72
measure: 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)
timeFrame: From baseline upto week 72
measure: Change in noninvasive biomarkers (NAFLD fibrosis score)
timeFrame: From baseline upto week 72
measure: Change in noninvasive biomarkers (FIB4 index)
timeFrame: From baseline upto week 72
measure: Change in noninvasive biomarkers (NAFIC score)
timeFrame: From baseline upto week 72
measure: Change in noninvasive biomarkers (ELF test)
timeFrame: From baseline upto week 72
measure: Percentage of patients with ≥ 30% reduction in hepatic fat fraction (MRI-PDFF)
timeFrame: From baseline upto week 72
measure: Percentage of patients with ≥ 15% reduction in liver stiffness (MRE)
timeFrame: From baseline upto week 72
Other outcomes:
Locations:
city: Aomori, Aomori
country: Japan
facility: Aomori Prefectural Central Hospital
city: Asahikawa, Hokkaido
country: Japan
facility: Asahikawa Medical University
city: Chuo-ku, Tokyo
country: Japan
facility: Fukuwa Clinic
city: Fukuoka, Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Hamamatsu, Shizuoka
country: Japan
facility: SeireiHamamatsu General Hospital
city: Hamamatsu, Shizuoka
country: Japan
facility: Hamamatsu University Hospital
city: Iwata, Shizuoka
country: Japan
facility: Iwata City Hospital
city: Kakegawa, Shizuoka
country: Japan
facility: Chutoen General Medical Center
city: Kurume, Fukuoka
country: Japan
facility: Kurume University Hospital
city: Niigata, Niigata
country: Japan
facility: Niigata University Medical & Dental Hospital
city: Ogaki, Gifu
country: Japan
facility: Ogaki Municipal Hospital
city: Otsu, Shiga
country: Japan
facility: Shiga University of Medical Science Hospital
city: Sapporo, Hokkaido
country: Japan
facility: Hokkaido University Hospital
city: Yamagata, Yamagata
country: Japan
facility: Yamagata University Hospital
city: Yokohama, Kanagawa
country: Japan
facility: Saiseikai Yokohamashi Tobu Hospital
city: Yokohama, Kanagawa
country: Japan
facility: Yokohama City University Hospital
Study officials:
affiliation: Clinical Development Dept. Ⅰ
name: Ryohei Tanigawa
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.