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

NCT02681055 | Completed Phase 2 Results

• 1 other identifier: MN-001-NATG-201
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 3

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.

Conditions

Non-alcoholic Steatohepatitis; Hypertriglyceridemia; Non-alcoholic Fatty Liver Disease; Hypercholesterolemia

Keywords

NASH; NAFLD

Outcome Measures

Primary Outcomes (2)

• 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.

  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

  8 weeks

Secondary Outcomes (5)

• Number of Treatment-emergent Adverse Events

  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

  24 hours

• Mean Serum Lipids From Baseline to Week 8

  Baseline, Week 8

• Mean Change in Liver Enzymes From Baseline to Week 8

  Baseline, Week 8

• Measure the Effect of MN-001/002 on Percentage of Fat in the Liver

  Baseline and Week 12

Study Arms (1)

open label arm

EXPERIMENTAL

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.

Drug: MN-001

Interventions

MN-001 DRUG

MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity

Also known as: tipelukast

open label arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent is obtained and willing and able to comply with the protocol in the opinion of the Investigator.
• Male or female subjects ≥ 18 years of age
• Histologically proven NASH (NAFLD activity score of 3 or greater with at least 1 point being ballooning) based on liver biopsy performed within the last 36 months or abdominal ultrasound confirmation of non-alcoholic fatty liver disease (NAFLD)
• Fasting serum triglyceride level \> 150 mg/dL (confirmed at screening)
• Serum ALT, AST, ALP and total bilirubin levels at Screening (- 120 days to -30 days) and Lab Visit values (- 1 week ± 5 days) are stable or changes at the Lab visit are \< 20% of the values from Screening.
• BMI ≤ 45 kg/m2
• Subjects on the following medications can be enrolled if these medications are necessary, cannot be stopped, and the dose has been stable for 4 months or more prior to baseline:
• Stable doses of anti-diabetic medications
• Stable doses of fibrates, statins, niacin, ezetimibe.
• Stable doses of Vitamin E for at least 8 weeks
• Less than 21 units of alcohol/week for men and 14 units of alcohol/week for women over a 2-year time frame
• Females of child-bearing potential must have a negative serum ß-hCG at screening and must be willing to use appropriate contraception (as defined by the investigator) for the duration of study treatment and 30 days after the last dose of study treatment.
• Males should practice contraception as follows: condom use and contraception by female partner.
• Subject is in good physical health on the basis of medical history, physical examination, and laboratory screening, as defined by the investigator.
• Subject is willing and able to comply with the protocol assessments and visits, in the opinion of the study nurse/coordinator and the Investigator.

You may not qualify if:

• Diagnosis of other known cause of liver disease (autoimmune, viral, genetic, drug- or alcohol-induced, or storage disease)
• Decompensated or severe liver disease defined by one or more of the following:
• biopsy-proven cirrhosis
• INR \>1.5
• Total bilirubin (TBL) \> 1.5 x ULN, or \> 2 x ULN for unconjugated bilirubin
• serum albumin \<2.8 g/dL
• ALT or AST \> 10 x ULN
• evidence of portal hypertension including splenomegaly, ascites, encephalopathy and/or esophageal varices
• Current diagnosis of hepatocellular carcinoma (HCC) or suspicion of HCC clinically or on ultrasound
• Uncontrolled diabetes mellitus Type 2
• History of bariatric surgery
• Greater than 10-pound weight gain or loss in the last 6 months
• Clinically significant cardiovascular/cerebrovascular disease, including myocardial infarct within last 6 months, coronary artery intervention, coronary artery bypass, unstable ischemic heart disease, heart failure class III or IV, angina or cerebral vascular accident.
• Resting pulse \< 50 bpm, SA or AV block, uncontrolled hypertension, or QTcF \> 450 ms
• History of stomach or intestinal surgery or any other condition that could interfere with or is judged by the Investigator to interfere with absorption, distribution, metabolism, or excretion of study drug.

Sponsors & Collaborators

• MediciNova: lead

Study Sites (3)

Southern California Research Center

Coronado, California, 92118, United States

Location

Scripps Research

La Jolla, California, 92037, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Hypertriglyceridemia; Hypercholesterolemia

Interventions

4-(6-acetyl-3-(3-(4-acetyl-3-hydroxy-2-propylphenylthio)propoxy)-2-propylphenoxy)butyric acid

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Director, Research and Development
• Organization: MediciNova, Inc.

makhay@medicinova.com

8583444535

Study Officials

• Kazuko Matsuda, MD PhD MPH

  MediciNova

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2016
• First Posted: February 12, 2016
• Study Start: March 1, 2016
• Primary Completion: May 30, 2018
• Study Completion: October 1, 2019
• Last Updated: March 15, 2023
• Results First Posted: March 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)