A Randomized, Double-Blind, Placebo-Controlled, Parallel Group, Multiple Dose Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of BMS-986263 in Adults With Advanced Hepatic Fibrosis After Virologic Cure of Hepatitis C
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 61
- 试验地点
- 1
- 主要终点
- The Number of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (METAVIR Score) as Determined by Liver Biopsy After 12 Weeks of Treatment
研究概览
简要总结
This is a study of experimental medication BMS-986263 in adult patients with advanced hepatic fibrosis (scar tissue in the liver caused by inflammation that is far on in progress) after the patient is cured of hepatitis C (an infection caused by a virus that attacks the liver and leads to inflammation).
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
- 21 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must provide documentation showing a sustained virologic response (SVR) for at least 1 year (52 weeks) prior to the date of screening (SVR is defined as a negative hepatitis C RNA greater than or equal to 12 weeks from the end of therapy)
- •Participants must have METAVIR Stage 3 or 4 (or equivalent if using other classification; eg, Ishak)
排除标准
- •Other causes of liver disease (eg, alcoholic liver disease, HBV [serologically positive as determined using United States Centers for Disease Control and Prevention guidance for interpretation of hepatitis B serologic test results], autoimmune hepatitis, drug-induced hepatotoxicity, Wilson disease, iron overload, alpha-1-antitrypsin deficiency, NASH, hemochromatosis)
- •Participants having liver diseases associated with infection with any other hepatitis virus
- •Detectable HCV RNA at screening
- •Child-Pugh score > 6
- •Model for End-Stage Liver Disease score >12
- •Evidence of HCC at screening based on alpha-fetoprotein (AFP) levels: AFP > 100 ng/mL (> 82.6 IU/mL) OR AFP ≥ 50 and ≤ 100 ng/mL (≥ 41.3 IU/mL and ≤ 82.6 IU/ mL) with liver ultrasound showing findings suspicious for HCC, or any imaging technique (eg, magnetic resonance imaging [MRI] or computed tomography; based on local assessment), or ultrasound
- •Blood transfusion in the last 6 months prior to screening due to the risk of re-infection with HCV, HBV, HIV, etc
- •Participant has any disease or condition which, in the opinion of the investigator, might compromise patient safety (eg, hematologic, cardiovascular, pulmonary, renal, gastrointestinal, hepatic, skeletal, central nervous system, or compliment-mediated disease); or other conditions that may interfere with the absorption, distribution, metabolism, or excretion of BMS 986263, or would place the participant at increased risk
- •Other protocol defined inclusion/exclusion criteria could apply
研究组 & 干预措施
Part 1 BMS-986263 45mg weekly
干预措施: BMS-986263 (Drug)
Part 1 BMS-986263 90mg weekly
干预措施: BMS-986263 (Drug)
Part 1 Placebo weekly
干预措施: Placebo (Other)
Part 2 BMS-986263 45mg every 2 weeks
干预措施: BMS-986263 (Drug)
Part 2 BMS-986263 90mg every 2 weeks
干预措施: BMS-986263 (Drug)
Part 2 BMS-986263 90mg every 4 weeks
干预措施: BMS-986263 (Drug)
Part 2 Placebo every 2 weeks
干预措施: Placebo (Other)
结局指标
主要结局
The Number of Participants Who Achieve ≥ 1 Stage Improvement in Liver Fibrosis (METAVIR Score) as Determined by Liver Biopsy After 12 Weeks of Treatment
时间窗: Week 12
The number of participants who achieve ≥ 1 stage improvement in liver fibrosis is used to asses the effects of treatment compared to placebo. The METAVIR system is used to assess the extent of inflammation and fibrosis by histopathological evaluation in a liver biopsy of patients with hepatitis C virus (HCV). It assesses liver biopsies for activity grade (A0-A3) and fibrosis stage (Stage 1 - 4). Participants without a measurement at Week 12 are considered non-responders. Activity Grade: A0 = no activity; A1 = mild activity; A2 = moderate activity; A3 = severe activity Fibrosis stage: 1 = portal fibrosis without septa ; 2 = portal fibrosis with few septa; 3 = numerous septa without cirrhosis; 4 = cirrhosis
次要结局
- Change From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) Day 85(Baseline and day 85)
- Change From Baseline in Collagen Proportionate Area (CPA) After 12 Weeks of Treatment(Baseline and Week 12)
- The Number of Participants With ≥ 1 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment(Week 12)
- The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (METAVIR Score) After 12 Weeks of Treatment(Week 12)
- The Number of Participants With ≥ 2 Stage Improvement in Liver Fibrosis (Ishak Score) After 12 Weeks of Treatment(Week 12)
- The Number of Participants With ≥ 15% Decrease From Baseline in Liver Stiffness as Measured by Magnetic Resonance Elastography (MRE) at Day 85(Baseline and day 85)