Study of Oral Idebenone to Treat Non-Alcoholic Steatohepatitis

Stanford University53 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Non Alcoholic Steatohepatitis Fibrosis

Interventions

IdebenoneDRUG

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.

PlaceboDRUG

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (2)

Digestive Health Center, Stanford University

Redwood City, California, United States

Stanford University

Stanford, California, United States

Outcomes

Primary Outcomes

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), and number of participants with abnormal Physical exams and abnormal laboratory tests results are reported.

Time frame: 60 weeks

Secondary Outcomes

Change in Magnetic Resonance Elastography (MRE) as a Measure of Change in Fibrosis Stage

MR elastography is a standard of care technique to assess liver stiffness, that is a highly accurate non-invasive method. MRE creates elastograms (stiffness maps) and data generated in kilopascals (kPa) are correlated to fibrosis stage. Change in stiffness values indicate change in fibrosis. \< 2.5 kPa: normal; 2.5 to 3.0 kPa: normal or inflammation; 3.0 to 3.5 kPa: stage 1-2 fibrosis; 3.5 to 4.0 kPa: stage 2-3 fibrosis; 4.0 to 5.0 kPa: stage 3-4 fibrosis; \> 5.0 kPa: Stage 4 fibrosis or cirrhosis.

Time frame: Week 48

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.