CM-101 in NASH Patients - The SPLASH Study

Exclusion Criteria

• •Patients with medical/surgical history of bariatric surgery procedures or bariatric device insertion or patients that are planned for such interventions;
• •Patients taking weight loss medications;
• •Evidence of drug induced steatohepatitis secondary to amiodarone, corticosteroids, estrogens, methotrexate, tetracycline, or other medications known to cause hepatic steatosis;
• •History or presence of cirrhosis (compensated or decompensated) determined by histology or relevant medical complications and laboratory parameters;
• •Model for End-stage Liver Disease (MELD) score \>12;
• •History of liver transplant, or current evaluation for or placement on a liver transplant waiting list;
• •Abnormal laboratory screening values:
• •1. Hemoglobin \< 12.0 g/dL in males and \< 11.0 g/dL in females
• •2. Platelet count \< 140,000/mm3
• •3. Total white blood cells (WBC) \< 3,000 cells/mm3
• •4. Absolute neutrophil count (ANC) \< 1,500 cells/mm3
• •5. Serum albumin \< 3.5 g/dL
• •Screening ECG demonstrating prolongation of QT interval corrected by Fredericia Correction Formula (QTcF) of \> 500 msec, or a history of clinically significant arrythmias
• •History of other chronic liver diseases including:
• •1. Alcoholic liver disease
• •2. Hepatitis B as defined by presence of hepatitis B surface antigen (HBsAg)
• •3. Hepatitis C as defined by presence of hepatitis C virus antibody (HCV-Ab) even if successfully treated with an antiviral regimen or positive HCV RNA (if necessary)
• •4. History or evidence of well documented autoimmune hepatitis (i.e. specific autoantibodies, hypergammaglobulinemia, consistent histologic changes)
• •5. History or evidence of primary biliary cholangitis (PBC)
• •6. History or evidence of primary sclerosing cholangitis (PSC)
• •7. History or evidence of Wilson's disease
• •8. History or evidence of alpha-1-antitrypsin deficiency
• •9. History or evidence of hemochromatosis
• •10. History or evidence of drug-induced liver disease, as defined on the basis of typical exposure and history
• •11. Known bile duct obstruction or a history of prior biliary tract diversion
• •12. Suspected or proven liver cancer;
• •History of human immunodeficiency virus (HIV) infection (positive HIV Ab);
• •Patients with diabetes mellitus type 1;
• •Patients with decompensated diabetes mellitus type 2 defined as either a HbA1c ≥ 9.5% at the time of screening or patients who are insulin dependent;
• •Patients under evaluation for a suspected malignancy, with any history of hepatocellular carcinoma (HCC), or a history of other malignancy diagnosed or treated within 2 years prior to Randomization (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to Screening);
• •Patients showing deleterious effects of alcohol abuse (as assessed by the investigator) or that consume excessive amounts of alcohol (\>14 units/week for both females and males; for the purposes of this study one unit of alcohol is considered to be equal to 8 gr);
• •Patients treated with chronic medication including but not limited to anti-retrovirals, tamoxifen, methotrexate, cyclophosphamide, isotretinoin, bile acid binding resins, obeticholic acid, ursodeoxycholic acid or pharmacologic doses of oral glucocorticoids (≥ 10 mg of prednisone per day or equivalent) within 12 weeks of Randomization
• •Significant systemic or major illness other than liver disease including:
• •1. Acute coronary syndrome, unstable angina, congestive heart failure, or cerebrovascular event within 24 weeks prior to Randomization
• •2. Major surgery within 12 weeks prior to Randomization
• •3. CNS disorders including Alzheimer's disease or other forms of dementia, seizure disorders and Parkinson's disease
• •4. Autoimmune disease that has required systemic treatment in the 2 years preceding the study screening (i.e., with the use of disease-modifying agents, corticosteroids or immunosuppressive drugs)
• •5. Uncontrolled thyroid disease
• •6. Clinically significant renal dysfunction (estimated GFR \< 60 ml/min (CKD equation))
• •7. A history of any clinically significant medical disorder that, in the judgement of the investigator, would interfere with patient treatment, assessment, or compliance with the protocol;
• •Known severe allergic or anaphylactic reactions to recombinant therapeutic proteins, fusion proteins, or chimeric, human, or humanized antibodies;
• •Patients with any other clinically significant disorders or prior therapy that, in the opinion of the investigator, would make the subject unsuitable for the study or unable to comply with the dosing and protocol requirements.
• •Participation in a study of another investigational agent within 28 days or five half-lives of the drug (whichever is longer) prior to screening;
• •Prior treatment with CM-101 antibody