A Phase 3, Double-Blind, Randomized, Long-Term, Placebo-Controlled, Multicenter Study Evaluating the Safety and Efficacy of Obeticholic Acid in Subjects With Nonalcoholic Steatohepatitis
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 2,477
- 试验地点
- 343
- 主要终点
- Time to the First Adjudicated Event for Clinical Outcome Composite Endpoint: Percentage of Participants With an Event
研究概览
简要总结
The primary objectives of this study are to evaluate the effect of Obeticholic Acid treatment compared to placebo on 1) histological improvement and 2) liver-related clinical outcomes in patients with non-cirrhotic nonalcoholic steatohepatitis (NASH) with liver fibrosis.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologic evidence of NASH upon central read of a liver biopsy obtained no more than 6 months before Day 1 defined by presence of all 3 key histological features of NASH according to NASH CRN criteria.
- •Histologic evidence of fibrosis stage 2 or stage 3 as defined by the NASH CRN scoring of fibrosis, or
- •Histologic evidence of fibrosis stage 1a or stage 1b if accompanied by ≥1 of the following risk factors:
- •Obesity (BMI ≥30 kg/m2)
- •Type 2 diabetes diagnosed per 2013 American Diabetes Association criteria
- •ALT >1.5× upper limit of normal (ULN).
- •For subjects with a historical biopsy, is either not taking or is on stable doses of TZDs/glitazones or vitamin E for 6 months before Day
- •Stable body weight.
排除标准
- •Model for End-stage Liver Disease (MELD) score >12
- •ALT ≥10× ULN
- •HbA1c >9.5%
- •Total bilirubin >1.5 mg/dL
- •Evidence of other known forms of known chronic liver disease such as alcoholic liver disease, hepatitis B, hepatitis C, PBC, PSC, autoimmune hepatitis, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, drug-induced liver injury, known or suspected hepatocellular carcinoma (HCC)
- •History of liver transplant, or current placement on a liver transplant list
- •Current or history of significant alcohol consumption
- •Prior or planned ileal resection, or prior or planned bariatric surgery
- •Histological presence of cirrhosis
- •History of biliary diversion
- •Known positivity for human immunodeficiency virus infection.
- •Acute cholecystitis or acute biliary obstruction.
- •BMI >45 kg/m2
研究组 & 干预措施
10 mg Obeticholic Acid
10 mg Obeticholic Acid daily for the remainder of the study
干预措施: Obeticholic Acid (Drug)
25 mg Obeticholic Acid
25 mg Obeticholic Acid daily for the remainder of the study
干预措施: Obeticholic Acid (Drug)
Placebo
One tablet daily for the remainder of the study
干预措施: Placebo (Drug)
结局指标
主要结局
Time to the First Adjudicated Event for Clinical Outcome Composite Endpoint: Percentage of Participants With an Event
时间窗: Up to 7 years
All potential liver-related clinical outcomes that occurred after administration of first dose of investigational product were reviewed and adjudicated by blinded, independent Hepatic Outcomes Committee(HOC). Adjudicated results were used to assess effect of OCA, compared to placebo in conjunction with established local standard of care, on clinical outcomes in participants with NASH as measured by time to first occurrence of any of following adjudicated events, derived as a composite event endpoint of death(all-cause), liver transplant, Model of End-stage Liver Disease(MELD)≥15 Score, hospitalization(defined by a stay of 24 hours or greater) for onset of: variceal bleed, hepatic encephalopathy(defined by a West Haven score of ≥2), and spontaneous bacterial peritonitis(confirmed by diagnostic paracentesis), ascites secondary to cirrhosis requiring medical intervention, and histological progression to Cirrhosis. Clinical events distribution was estimated using Kaplan-Meier methodology.
次要结局
- Percentage of Responders With Improvement of Fibrosis by at Least One Stage With no Worsening of NASH Using Consensus Read Method of Scheduled Liver Biopsies(Up to 7 years)
- Percentage of Participants Who Showed Improvement in Fibrosis by at Least 1 Stage and/or Resolution of NASH Without Worsening of Either Using Consensus Read Method(Up to 7 years)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(Up to 7 years)