Study of Oral Idebenone to Treat Non-Alcoholic Steatohepatitis

A Pilot Study to Treat Adults With Non-Alcoholic Steatohepatitis With Oral Idebenone

This is a randomized, placebo-controlled phase 1/2a study to investigate the safety and tolerability of Idebenone in patients 18 years of age or older with non-alcoholic steatohepatitis, with stage 1-3 fibrosis. As secondary end point target engagement and fibrosis improvement will be assessed.

This is a prospective phase 1/2a, randomized, double-blinded, placebo-controlled, single center study of safety and efficacy of oral idebenone in adults 18 years of age or older with non-alcoholic steatohepatitis (NASH). Following IRB approval and written informed consent, 45 participants will be enrolled in the study and randomized in a 1:2 ratio on REDCap data capturing software. Participants will be randomized to two groups and receive the following tablets: placebo, idebenone at escalating doses of 200mg by mouth (P.O.) once a day for 2 weeks, then 200 mg twice a day for 2 weeks, then 3 times per day for the remainder of the study (up to 48 weeks). Monitoring and safety evaluation will continue for 12 weeks after the final dose. The study will investigate the safety and tolerability as primary end point and assess target engagement and fibrosis improvement as secondary end points.

Inclusion Criteria:

• 1) Male or non-pregnant/ non-lactating women ≥ 18 years of age

• 2) Diagnosis of NASH: NAFLD activity score (NAS) of 4 or greater with a score of 1 for each of the following (steatosis scored 0-3, lobular inflammation scored 0-3, ballooning scored 0-2):

  • Steatosis
  • Lobular inflammation
  • Hepatocyte ballooning 3) Fibrosis (Ishak fibrosis score ≥1 on liver biopsy) within 6 months of enrollment with MELD<10, or based on MRE

Exclusion Criteria:

• Presence of any other form of liver disease, including viral hepatitis, autoimmune hepatitis, alcoholic liver disease, genetic causes of chronic liver disease):

• Subjects with other etiologies of chronic liver disease, such as chronic hepatitis B and C; autoimmune hepatitis; and inherited liver disease.

• ALT>300 U/l

• Total serum bilirubin ≥ to 1.3 mg/dL (Gilbert's Syndrome patients excepted)

• International Normalized Ratio (INR) ≥ 1.3

• MELD>10

• Serum creatinine >2.0mg/dl

• Known alcohol abuse or alcohol use disorder:

  • >20 g/day for women
  • >30 g/day for men

• Active substance abuse

• Any medical condition that prevents MRE, MR-PDFF

• Platelet count ≤100//mm3

• Decompensated cirrhosis

• Hemoglobin <11 g/dl in females or <12 g/dl in males

• Presence/history of HCC

• History of liver transplantation

• History of bariatric surgery

• History of inflammatory bowel disease

• History of cardiovascular disease, long QT syndrome.

• Subjects who have participated in investigational drug trials and took any investigational drugs within 60 days prior to the first dose of Idebenone. History of receiving other investigations drug within 30 days prior to enrollment

• Any concerns regarding compliance by enrolling physician