Study of Oral Idebenone to Treat Non-Alcoholic Steatohepatitis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Non Alcoholic Steatohepatitis

Intervention / Treatment
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* Drug: Idebenone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Idebenone<br>Participants will take Idebenone 200 mg for 48 weeks, with study visits in clinic for physical and laboratory assessments at weeks 0, 2, 4, 12, 24, 36, and 48 weeks during treatment period and at 4, and 12 weeks after the last dose. | Drug: Idebenone<br>* Idebenone, initially 200mg by mouth (P.O.) once a day for 2 weeks, then 200 mg twice a day for 2 weeks, then 200 mg three times per day for the remainder of the study will be used.<br>* Other names: Placebo;|
| Placebo Comparator: Placebo<br>Participants will take Placebo for 48 weeks, with study visits in clinic for physical and laboratory assessments at weeks 0, 2, 4, 12, 24, 36, and 48 weeks during treatment period and at 4, and 12 weeks after the last dose. | Drug: Placebo<br>* Placebo to match Idebenone once a day for 2 weeks, then twice a day for 2 weeks, then three times per day for the remainder of the study will be used.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | Number of Participants with Treatment-Related Adverse Events (Assessed by CTCAE v4.0, including abnormal Physical exams and abnormal laboratory tests results will be reported. | Week 60: Assessment of AEs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fibrosis stage | Number of Participants with change in fibrosis stage | Week 48: fibrosis change |