Phase Ib/II Study to Evaluate the Efficacy and Safety of GH509 Versus Placebo in Patients With NASH/NAFLD

Exclusion Criteria

• •1. Subjects with a history of significant alcohol consumption for a period of more than 3 consecutive months any time within 1 year prior to screening.
• •2. Use of injected or oral antidiabetic agents within 3 months including: Thiazolidinediones; Subcutaneously administered agents; Sodium-glucose co-transporter 2 inhibitors
• •3. Patients with a history of hypoglycemia within 3 months before study enrollment.
• •4. Subject uses drugs historically associated with NASH/NAFLD for more than 2 weeks in the year prior to randomization.
• •5. Treatment with a non-stable dose of statins, fibrates, or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor in 3 months prior to randomization.
• •6. LDL ≥190 mg/dL.
• •7. Treatment with a non-stable dose of drugs with potential anti-NASH/NAFLD effect in the 6 months prior to randomization.
• •8. Participated in a clinical research study with any investigational product being evaluated for the treatment of diabetes, weight loss, or NASH/NAFLD in the 6 months prior to randomization.
• •9. Subject is listed for orthotopic liver transplant (OLT) or has medical history of: biliary diversion, organ transplant/bone marrow transplant or undergoing immunosuppressive therapy, hepatocellular, pancreatic, thyroid carcinoma, multiple endocrine neoplasia syndrome type 2 (MEN 2) or other malignant disease.
• •10. Subject has prior or has planned bariatric surgery.
• •11. Subject had major surgery within 8 weeks prior to randomization, significant traumatic injury, or anticipation of need for major surgical procedure during the course of the study.
• •12. Presence of cirrhosis on liver biopsy.
• •13. Model for End-stage Liver Disease (MELD) score greater than 12.
• •14. Subject with clinical evidence of hepatic decompensation.
• •15. Subject has evidence of other forms of chronic liver disease:.
• •16. Acute cholecystitis or known biliary obstruction.
• •17. Acute or chronic pancreatitis or administration of total parenteral nutrition within 6 months prior to randomization.
• •18. Subject has gastrointestinal disorder(s) which would significantly impede the absorption of an oral agent.
• •19. Subject has concurrent severe infection including diagnoses of fever of unknown origin.
• •20. Clinically significant and uncontrolled cardiovascular disease within 12 months prior to randomization; cerebrovascular disease, grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication or grade II or greater peripheral vascular disease.
• •21. Subject with history of human immunodeficiency virus (HIV) infection.
• •22. Subject with known allergies to the study drug or any of its excipients.
• •23. Subject with an active, serious medical disease with likely life expectancy of less than 5 years.
• •24. Subject with active substance abuse, including alcohol and/or inhaled or injection drugs, in the year prior to randomization.
• •25. Subject has participated in an investigational new drug (IND) trial in the 30 days before randomization.
• •26. Subject has been previously exposed to GH509.
• •27. Unable or unwilling to swallow GH509/placebo daily.
• •28. Ineligibility for MRI.
• •29. Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.
• •30. Subject has any other condition which would impede compliance or hinder completion of the study.