This is a multi-center, proof-of-principle, open-label study designed to evaluate the efficacy, safety, and tolerability of MN-001 in non-alcoholic steatohepatitis (NASH) and Non-Alcoholic Fatty Liver Disease (NAFLD) subjects with hypertriglyceridemia.
The study will consist a Screening Phase (up to 4 months) followed by a Treatment Phase (12 weeks), and a Follow-up visit (within 1 week after the last dose). A total of 40 male and female subjects ≥18 years of age are planned to be enrolled. During the Screening Phase, subjects will be assessed for study eligibility. After signing the informed consent form, the following assessments will be performed: medical history including review of prior and current medications, physical examination including height and body weight, waist circumference, vital signs and an electrocardiogram. Clinical labs, routine chemistries, hematology, coagulation profile, urinalysis and a serum pregnancy test will be collected as well as cytokeratin-18 (CK-18), a biomarker for NASH diagnosis. An alcohol consumption questionnaire will be administered and a MRI scan of the liver will be performed. Serum fibrosis markers, the Fib-4 index (age, AST, ALT, PLT) and NAFLD fibrosis score (age, BMI, AST/ALT ratio, IFG/DM, PLT, Albumin) will be calculated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Southern California Research Center
Coronado, California, United States
Scripps Research
La Jolla, California, United States
Harborview Medical Center
Seattle, Washington, United States
Mean Change From Baseline at 12 Weeks of MN-001 Treatment on Cholesterol Efflux Capacity
Change from baseline to 12 weeks of MN-001 on Cholesterol Efflux Capacity (CEC) in NAFLD subjects with hypertriglyceridemia. CEC, a key step in reverse cholesterol transport, was inversely associated with the incidence of cardiovascular events and is considered to be a new biomarker to assess cardiovascular risk. Cholesterol efflux was calculated as the percent of cholesterol removed from the cells and appearing in the culture medium normalized to a reference serum pool. The ability of serum HDL to remove cholesterol from cultured cells was assessed as an in vitro method to evaluate functional changes in HDL mediated by changes due to MN-001 treatment.
Time frame: Baseline, 12 weeks
Mean Change From Baseline to Week 8 on Triglyceride Levels After 8 Weeks MN-001 Treatment
Change from baseline to 8 weeks of MN-001 on serum triglyceride levels in NASH subjects with hypertriglyceridemia
Time frame: 8 weeks
Number of Treatment-emergent Adverse Events
Safety and tolerability of MN-001 by assessing the number of subjects who experienced treatment-emergent adverse events. A treatment-emergent adverse event is defined as any untoward medical occurrence in a participant, which does not necessarily have a causal relationship with the trial intervention.
Time frame: Baseline, Weeks 2, 4, 8, 12 and 13
Mean Plasma Concentration of MN-001 and MN-002 (Metabolite) After a Single Dose of MN-001 in Six Subjects
Mean plasma concentration of of MN-001 and its metabolite, MN-002, after a single 250 mg oral dose of MN-001 in nonalcoholic steatohepatitis and nonalcoholic fatty liver disease patients.
Time frame: 24 hours
Mean Serum Lipids From Baseline to Week 8
Mean change from baseline to week 8 on total cholesterol, high-density lipoproteins, low-density lipoproteins
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Time frame: Baseline, Week 8
Mean Change in Liver Enzymes From Baseline to Week 8
Measure the effect of MN-001/002 on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) mean change from Baseline to Week 8
Time frame: Baseline, Week 8
Measure the Effect of MN-001/002 on Percentage of Fat in the Liver
To measure the effect of MN-001/002 on percentage of fat in the liver by MRI mean change from baseline to Week 12
Time frame: Baseline and Week 12