Study of Oral Idebenone to Treat Non-Alcoholic Steatohepatitis

Sponsor

Stanford University (Other)

Overall Status

Recruiting

CT.gov ID

NCT04669158

Collaborator

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

Enrollment

Locations

Arms

Anticipated Duration (Months)

22.5

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

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

Anticipated 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

Anticipated Study Start Date :

Jul 30, 2021

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Mar 1, 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 Names: 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.

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 Names:

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

Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0 [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

Change in fibrosis stage [Week 48: fibrosis change]
Number of Participants with change in fibrosis stage

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

	Site	City	State	Country	Postal Code
1	Digestive Health Center, Stanford University	Redwood City	California	United States	94063
2	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Natalie Torok, Professor, Stanford University

ClinicalTrials.gov Identifier:

NCT04669158

Other Study ID Numbers:

52212
R21DK111217

First Posted:

Dec 16, 2020

Last Update Posted:

Jul 23, 2021

Last Verified:

Jul 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Fatty Liver

Non-alcoholic Fatty Liver Disease

Idebenone

Study Results

No Results Posted as of Jul 23, 2021