NCT02686762已完成2 期
A Multicenter, Randomized, Double-Blind, Placebo-controlled Trial of Emricasan (IDN-6556-12), an Oral Caspase Inhibitor, in Subjects With Non-alcoholic Steatohepatitis (NASH) Fibrosis
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 318
- 试验地点
- 103
- 主要终点
- Fibrosis improvement by at least one stage without worsening of steatohepatitis
研究概览
简要总结
This is a multicenter, double-blind, randomized, placebo-controlled trial involving subjects with a diagnosis of "definite NASH" with fibrosis (excluding cirrhosis) as determined by the central histopathologist. Upon successful screening, subjects will be randomized to receive either emricasan 50 mg BID or emricasan 5 mg BID or matching placebo BID.
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, Investigator, Outcomes Assessor)
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
- •Male or female subjects 18 years or older, able to provide written informed consent, and able to understand and willing to comply with the requirements of the study
- •Histological evidence of definite NASH based on NASH CLinical Research Network (CRN) criteria, as confirmed by the central histopathologist, on a liver biopsy obtained no more than 6 months prior to Day 1
- •NAFLD Activity Score (NAS) of 4 or greater with a score of at least 1 in each component of the NAS (steatosis scored 0-3, lobular inflammation scored 0-3, ballooning scored 0-2)
- •Fibrosis stage 1 (limited to 20% of subjects), stage 2, or stage 3 using the NASH CRN Histologic Scoring System
- •a. Subjects with fibrosis stage 1 must also have diabetes mellitus or metabolic syndrome
- •Willingness to utilize effective contraception (for both males and females of childbearing potential) from Screening to 4 weeks after the last dose of study drug
- •If on vitamin E or pioglitazone, subjects must have been on a stable dose for at least 3 months prior to the biopsy (whether historical or qualifying biopsy)
排除标准
- •Current or history of significant alcohol consumption, defined as more than 20 g/day for females and more than 30 g/day in males on average, or inability to reliably quantify alcohol consumption based on investigator's judgement
- •Use of the following drugs (which may have potential hepatotoxic effects) within 6 months prior to Day 1: amiodarone, methotrexate, tamoxifen, valproic acid, estrogens at doses greater than those used for hormone replacement or contraception, anabolic steroids, or systemic glucocorticoids for more than 4 weeks at doses greater than replacement doses
- •Uncontrolled diabetes (HbA1c ≥9%) within 60 days prior to Day 1
- •Presence of cirrhosis on liver biopsy (fibrosis stage 4 based on the central histopathologist reading)
- •Hepatitis and fibrosis more likely related to etiologies other than NASH such as:
- •alcoholic steatohepatitis
- •autoimmune hepatitis
- •hepatitis B virus (HBV) infection
- •hepatitis C virus (HCV) infection
- •primary biliary cirrhosis
- •primary sclerosing cholangitis
- •Wilson's disease
- •alpha-1-antitrypsin deficiency
- •hemochromatosis or iron overload
- •drug-induced liver disease
- •other biliary liver disease
- •ALT or AST >5 times upper limit of normal (ULN) or total bilirubin >1.5 times ULN during screening (unless subject has elevated total bilirubin due to Gilbert's as documented in the medical records)
- •Alpha-fetoprotein >200 ng/mL
- •Hemoglobin <10 g/dL
- •White blood cell count <2.0 x 10^3/mm3
- •Estimated creatinine clearance <30 mL/min
- •Current use of the following medications that are considered significant inhibitors of OATP1B1 and OATP1B3 transporters: atazanavir, cyclosporine, eltrombopag, gemfibrozil, indinavir, lopinavir, ritonavir, rifampin, saquinavir, simeprevir, telaprevir, tipranovir, or some combination of these medications
- •Symptoms of biliary colic, e.g. due to symptomatic gallstones, within the last 6 months, unless resolved following cholecystectomy
- •Inability to safely obtain a liver biopsy
- •Known human immunodeficiency virus (HIV) infection
- •Weight loss ≥ 10% within 6 months of Day 1
- •Use of controlled substances (including inhaled or injected drugs) or non-prescribed use of prescription drugs within 1 year of screening to the point of interfering with the subject's ability to comply with study procedures and study drug administration in the investigator's judgement
- •History of or active malignancies, other than those successfully treated with curative intent and believed to be cured
- •Significant systemic or major illness other than liver disease that in the opinion of the investigator would preclude the subject from participating in and completing the study, including but not limited to acute coronary syndrome or stroke within 6 months of screening or major surgery within 3 months of screening
- •History or presence of clinically concerning cardiac arrhythmias, or prolongation of Screening (pre-treatment) QTcF interval >480 milliseconds (msec)
- •Prior or planned (during the time frame of the study) bariatric surgery
- •If female: planned or known pregnancy, positive urine or serum pregnancy test, or lactating/breastfeeding
- •Previous treatment with emricasan or active investigational medication in a clinical trial within 6 months prior to Day 1
- •Prior liver transplant
研究组 & 干预措施
Emricasan (5 mg)
Active Comparator
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (5 mg) twice a day.
干预措施: Emricasan (5 mg) (Drug)
Emricasan (50 mg)
Active Comparator
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with emricasan (50 mg) twice a day.
干预措施: Emricasan (50 mg) (Drug)
Matching Placebo
Placebo Comparator
Subjects with Non-alcoholic Steatohepatitis (NASH) Fibrosis will be administered orally with a matching placebo twice a day.
干预措施: Placebo (Drug)
结局指标
主要结局
Fibrosis improvement by at least one stage without worsening of steatohepatitis
时间窗: Week 72
Proportion of subjects who improve fibrosis on liver biopsy by at least one stage without worsening of steatohepatitis in the emricasan group compared to placebo
次要结局
- Improvement in the Non-alcoholic fatty liver disease (NAFLD) Activity Score(Baseline & Week 72)
- Steatohepatitis resolution (based on liver biopsy)(Baseline & Week 72)
- Caspase 3/7 Relative Light Units and Alanine aminotransferase (ALT)(Day 1, week 4, 24, 48, and 72)
研究者
研究点 (103)
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