Open-Label Study To Evaluate MN-001 on HDL & Triglyceride in NASH & NAFLD Subjects

Phase 2

Completed

• Conditions: Non-alcoholic Steatohepatitis; Hypertriglyceridemia; Non-alcoholic Fatty Liver Disease; Hypercholesterolemia
• Interventions: Drug: MN-001

• Registration Number: NCT02681055
• Lead Sponsor: MediciNova

Brief Summary

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.

Detailed Description

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 Timeline

• Study First Submitted: 2016-02-05
• Study First Submitted QC: 2016-02-09
• Study First Posted: 2016-02-12
• Study Start: 2016-03
• Primary Completion: 2018-05-30
• Study Completion: 2019-10-01
• Disposition First Submitted: 2020-05-22
• Disposition First Submitted QC: 2020-05-22
• Disposition First Posted: 2020-05-26
• Results First Submitted: 2022-08-22
• Status Verified: 2023-02
• Results First Submitted QC: 2023-02-17
• Last Update Submitted: 2023-02-17
• Results First Posted: 2023-03-15
• Last Update Posted: 2023-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
open label arm	MN-001	All 40 subjects will receive MN-001 for the first 4 weeks. At Week 4 subjects will increase their dosage frequency for remaining 8 weeks. Subjects will receive MN-001 for a total of 12 weeks.

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline to Week 8 on Triglyceride Levels After 8 Weeks MN-001 Treatment	8 weeks	Change from baseline to 8 weeks of MN-001 on serum triglyceride levels in NASH subjects with hypertriglyceridemia
Mean Change From Baseline at 12 Weeks of MN-001 Treatment on Cholesterol Efflux Capacity	Baseline, 12 weeks	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.

Secondary Outcome Measures

Name	Time	Method
Number of Treatment-emergent Adverse Events	Baseline, Weeks 2, 4, 8, 12 and 13	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.
Mean Plasma Concentration of MN-001 and MN-002 (Metabolite) After a Single Dose of MN-001 in Six Subjects	24 hours	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.
Mean Serum Lipids From Baseline to Week 8	Baseline, Week 8	Mean change from baseline to week 8 on total cholesterol, high-density lipoproteins, low-density lipoproteins
Mean Change in Liver Enzymes From Baseline to Week 8	Baseline, Week 8	Measure the effect of MN-001/002 on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) mean change from Baseline to Week 8
Measure the Effect of MN-001/002 on Percentage of Fat in the Liver	Baseline and Week 12	To measure the effect of MN-001/002 on percentage of fat in the liver by MRI mean change from baseline to Week 12

Trial Locations

Locations (3)

Southern California Research Center; 🇺🇸 Coronado, California, United States

Scripps Research; 🇺🇸 La Jolla, California, United States

Harborview Medical Center; 🇺🇸 Seattle, Washington, United States