Open-Label Study To Evaluate MN-001 on HDL & Triglyceride in NASH & NAFLD Subjects
Condition: Non-alcoholic Steatohepatitis; Hypertriglyceridemia; Non-alcoholic Fatty Liver Disease; Hypercholesterolemia
MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypercholesterolemia; Hypertriglyceridemia
Intervention: MN-001
Intervention description: MN-001 is a novel, orally bioavailable small molecule compound which demonstrates anti-inflammatory activity
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 19.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: NASH; NAFLD

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.
    

Eligibility 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.