Study of Oral Idebenone to Treat Non-Alcoholic Steatohepatitis

• ClinicalTrials.gov Identifier: NCT04669158
• Recruitment Status: Active, not recruiting
• First Posted: December 16, 2020
• Last Update Posted: October 25, 2022
• Sponsor: Stanford University
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Natalie Torok, Stanford University

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Non Alcoholic Steatohepatitis	Drug: Idebenone; Drug: Placebo	Phase 1; Phase 2

Detailed Description:

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 45 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Pilot Study to Treat Adults With Non-Alcoholic Steatohepatitis With Oral Idebenone
• Actual Study Start Date: July 30, 2021
• Estimated Primary Completion Date: April 2023
• Estimated Study Completion Date: May 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Idebenone; 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; 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.; Other Name: Placebo
Placebo Comparator: Placebo; 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; 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.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [ Time Frame: Week 60: Assessment of AEs ]
   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.

Secondary Outcome Measures :

1. Change in fibrosis stage [ Time Frame: Week 48: fibrosis change ]
   Number of Participants with change in fibrosis stage

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

Digestive Health Center, Stanford University

Redwood City, California, United States, 94063

Stanford University

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Natalie Torok, MD; Stanford University

More Information

• Responsible Party: Natalie Torok, Professor, Stanford University
• ClinicalTrials.gov Identifier: NCT04669158
• Other Study ID Numbers: 52212; R21DK111217 ( U.S. NIH Grant/Contract )
• First Posted: December 16, 2020
• Last Update Posted: October 25, 2022
• Last Verified: October 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Fatty Liver; Non-alcoholic Fatty Liver Disease; Liver Diseases; Digestive System Diseases; Idebenone; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs