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Trial record 1 of 4 for:    mn-001
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Open-Label Study To Evaluate Efficacy, Safety, Tolerability & PK of MN-001 on HDL & Triglyceride in NASH & NAFLD Subjects

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by MediciNova
Sponsor:
Information provided by (Responsible Party):
MediciNova
ClinicalTrials.gov Identifier:
NCT02681055
First received: February 5, 2016
Last updated: August 10, 2017
Last verified: August 2017
  Purpose
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.

Condition Intervention Phase
Non-alcoholic Steatohepatitis Hypertriglyceridemia Non-alcoholic Fatty Liver Disease Drug: MN-001 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study To Evaluate The Efficacy, Safety, Tolerability and PK of MN-001 (Tipelukast) on HDL Function and Serum Triglyceride Levels in NASH and Non-Alcoholic Fatty Liver Disease (NAFLD) Subjects With Hypertriglyceridemia

Resource links provided by NLM:


Further study details as provided by MediciNova:

Primary Outcome Measures:
  • To evaluate the change from baseline at 12 weeks of MN-001 on Cholesterol Efflux Capacity in NASH subjects with hypertriglyceridemia [ Time Frame: Baseline, 12 weeks ]
  • To evaluate the change from baseline at 12 weeks of MN-001 on triglyceride levels in NASH subjects with hypertriglyceridemia [ Time Frame: Screening, Weeks 4, 8, 12 and 13 ]

Secondary Outcome Measures:
  • To evaluate the safety and tolerability of MN-001 by assessing the number of treatment-related adverse events. [ Time Frame: Baseline, Weeks 2, 4, 8, 12 and 13 ]
  • To evaluate blood the concentration of MN-001/MN-002 (metabolite) change from pre-dose after 24 hours [ Time Frame: Baseline ]
  • To evaluate the effect of MN-001 on lipid profile [ Time Frame: Baseline, Weeks 2, 4, 8, 12 and 13 ]
  • To evaluate the effect of MN-001/002 on liver enzymes [ Time Frame: Baseline, Weeks 2, 4, 8, 12 and 13 ]
  • To evaluate the effect of MN-001/002 on percentage of fat in the liver assessed using MRI from baseline up to Week 12 [ Time Frame: Baseline, Weeks 2, 4, 8, 12 and 13 ]

Estimated Enrollment: 40
Study Start Date: March 2016
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: open label arm
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
MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Other Name: tipelukast

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • 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.

EXCLUSION CRITERIA:

  • 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.
  • Any significant laboratory abnormality which, in the opinion of the Investigator, may put the subject at risk
  • History of malignancy < 5 years prior to signing the informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
  • History of HIV (human immunodeficiency virus), HBV, HCV (cured HCV is not excluded), EBV CMV or other active infection.
  • Currently has a clinically significant medical condition including the following: neurological, psychiatric, metabolic, immunologic, hematological, pulmonary, cardiovascular (including uncontrolled hypertension), gastrointestinal, urological disorder, or central nervous system (CNS) infection that would pose a risk to the subject if they were to participate in the study or that might confound the results of the study. Note: Active medical conditions that are minor or well-controlled are not exclusionary if, in the judgment of the Investigator, they do not affect risk to the subject or the study results. In cases in which the impact of the condition upon risk to the subject or study results is unclear, the Medical Safety Monitor should be consulted.
  • CYP2C8 substrates with a narrow therapeutic index (e.g., paclitaxel) within 15 days prior to study and throughout the study are prohibited.
  • CYP2C9 substrate with narrow therapeutic index (e.g., phenytoin, S-warfarin, tolbutamide) within 15 days prior to study and throughout the study are prohibited.
  • Macrolide or quinolone class antibiotics within 15 days of Screening Visit and throughout the study are prohibited.
  • Steroids within 30 days prior to study drug dosing and throughout the study unless administered for a short term treatment course during the study are prohibited.
  • History of alcohol or substance abuse (DSM-IV-TR criteria) within 3 months prior to screening or alcohol or substance dependence (DSM-IV-TR criteria) within 12 months prior to screening. The only exceptions include caffeine or nicotine abuse/dependence.
  • Poor peripheral venous access that will limit the ability to draw blood as judged by the Investigator.
  • Currently participating, or has participated in, a study with an investigational or marketed compound or device within 3 months prior to signing the informed consent.
  • Unable to cooperate with any study procedures, unlikely to adhere to the study procedures and keep appointments, in the opinion of the Investigator, or was planning to relocate during the study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02681055

Contacts
Contact: Paul J Pockros, MD 8585548879 Pockros.Paul@scrippshealth.org
Contact: Ronda K Willis, MBA (858) 692-9887

Locations
United States, Alabama
University of Alabama Withdrawn
Birmingham, Alabama, United States, 35294
United States, California
Southern California Research Center Recruiting
Coronado, California, United States, 92118
Contact: Karel Biandi    619-964-9649    kbiando@livercenters.com   
Contact: Yasmeen Esshaki    619-522-0330    yasmeen@livercenters.com   
Principal Investigator: Julio A Gutierrez, MD         
Scripps Clinic Recruiting
La Jolla, California, United States, 92037
Contact: Kaye Waite, RN CCRC    858-554-8931    Waite.Kaye@scrippshealth.org   
Principal Investigator: Paul J. Pockros, MD         
Sub-Investigator: Yuki Rosenkoetter, PA-C         
Sub-Investigator: Catherine Frenette, MD         
Sub-Investigator: Lori Rose, NP         
United States, Virginia
Inova Health Care Services Withdrawn
Falls Church, Virginia, United States, 22042
United States, Washington
Harborview Medical Center Recruiting
Seattle, Washington, United States, 98104
Contact: Peter Nguyen, BS    206-744-3402    phnguyen@medicine.washington.edu   
Contact: Lynn Gemmell, CRC MBA    206-744-7063    lgemmell@medicine.washington.edu   
Principal Investigator: Charles S Landis, MD, PhD         
Sponsors and Collaborators
MediciNova
Investigators
Study Director: Kazuko Matsuda, MD, PhD, MPH MediciNova, Inc.
  More Information

Responsible Party: MediciNova
ClinicalTrials.gov Identifier: NCT02681055     History of Changes
Other Study ID Numbers: MN-001-NATG-201
Study First Received: February 5, 2016
Last Updated: August 10, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by MediciNova:
NASH
NAFLD

Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Hypertriglyceridemia
Digestive System Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on August 18, 2017