Clinical trial NCT04669158: Study of Oral Idebenone to Treat Non-Alcoholic Steatohepatitis
Official title: A Pilot Study to Treat Adults With Non-Alcoholic Steatohepatitis With Oral Idebenone
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Non Alcoholic Steatohepatitis
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2020-12-16
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0
timeFrame: Week 60: Assessment of AEs
Secondary outcomes:
measure: Change in fibrosis stage
timeFrame: Week 48: fibrosis change
Other outcomes:
Locations:
city: Redwood City
country: United States
facility: Digestive Health Center, Stanford University
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
Study officials:
affiliation: Stanford University
name: Natalie Torok, MD
role: PRINCIPAL_INVESTIGATOR
References: