A Pilot Study to Treat Adults With Non-Alcoholic Steatohepatitis With Oral Idebenone
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 4
- 主要终点
- Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
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.
干预措施: Idebenone (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v4.0
时间窗: 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.
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
时间窗: 60 weeks
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.
次要结局
- Change in fibrosis stage(Week 48: fibrosis change)
- Change in Magnetic Resonance Elastography (MRE) as a Measure of Change in Fibrosis Stage(Week 48)
研究者
Natalie Torok
Professor
Stanford University