Study of Oral Idebenone to Treat Non-Alcoholic Steatohepatitis

Stanford University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Non Alcoholic Steatohepatitis; Fibrosis

Treatments: Drug: Placebo; Drug: Idebenone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04669158

R21DK111217 (U.S. NIH Grant/Contract)

52212

Details and patient eligibility

About

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.

Full 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.

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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45 participants in 2 patient groups, including a placebo group

Idebenone

Experimental group

Description:

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.

Treatment:

Drug: Idebenone

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo