A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Dose-Finding Study To Evaluate The Efficacy and Safety Of CC-90001 In Subjects With Non-Alcoholic Steatohepatitis (NASH) and Liver Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Celgene
- 入组人数
- 56
- 试验地点
- 142
- 主要终点
- Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52
研究概览
简要总结
This is a Phase 2, randomized, double-blind, placebo-controlled, multicenter, multinational, dose-finding study evaluating the efficacy of three treatment doses of CC-90001 compared with placebo, in Non-alcoholic Steatohepatitis (NASH) participants with Stage 2, Stage 3 liver fibrosis.
This study is designed to assess response to treatment on measures of fibrosis and other efficacy parameters. It will also assess dose response and overall safety.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Key Inclusion Criteria Diagnosis of non-alcoholic steatohepatitis (NASH) with presence of Stage 2, Stage 3 fibrosis based of the non-alcoholic steatohepatitis (NASH) Clinical Research Network (CRN) Histologic Scoring System and a nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) of 4 or higher
排除标准
- •Key Exclusion Criteria
- •History or evidence of decompensated liver disease,
- •Hepatitis and fibrosis more likely related to etiologies other than non-alcoholic steatohepatitis (NASH).
- •Participant has urine ethyl glucuronide (EtG) > 500 ng/mL at Screening.
- •History or positive screen for human immunodeficiency virus (HIV) infection or congenital or human immunodeficiency virus (HIV)-unrelated acquired immunodeficiencies (eg, common variable immunodeficiency [CVID]).
- •History of hepatitis B and/or hepatitis C.
- •History of malignancy within the last 5 years (exceptions: excised and cured basal/squamous cell skin carcinomas and cervical carcinoma in situ).
- •Pregnancy or lactation.
研究组 & 干预措施
CC-90001 400 mg once daily (QD)
CC-90001 400 mg QD
干预措施: CC-90001 (Drug)
CC-90001 200 mg once daily
CC-90001 200 mg QD
干预措施: CC-90001 (Drug)
CC-90001 100 mg once daily
CC-90001 100 mg QD
干预措施: CC-90001 (Drug)
Placebo once daily
Placebo QD
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants Who Achieve a ≥1 Stage Improvement in Liver Fibrosis Using the NASH CRN Histological Scoring System at Week 52
时间窗: From baseline up to week 52
Percentage of participants who achieve a ≥1 stage improvement in liver fibrosis using the NASH CRN Histological Scoring System at Week 52. A participant with a change of ≤ -1 from baseline in fibrosis stage is considered as an improvement responder for this endpoint. The NASH CRN Histologic Scoring System comprised: steatosis (0 to 3) lobular inflammation (0 to 3) hepatocellular ballooning (0 to 2) fibrosis disease stage (0 to 4) * Stage 0 - None; * Stage 1a - Mild (delicate) zone 3 perisinusoidal fibrosis; * Stage 1b - Moderate (dense) zone 3 perisinusoidal fibrosis; * Stage 1c - Portal/periportal fibrosis only; * Stage 2 - Zone 3 perisinusoidal fibrosis with portal/periportal fibrosis; * Stage 3 - Bridging fibrosis; * Stage 4 - Cirrhosis.
次要结局
- Mean Change From Baseline of ECG Results - QTcB Interval(From baseline up to week 52)
- Percentage of Participants With Resolution of NASH(From baseline up to week 52)
- Tmax(Day 1 and at Week 4)
- Mean Change From Baseline of ECG Results - PR Intervals(From baseline up to week 52)
- Percentage of Participants Who Progressed to Cirrhosis(From baseline up to week 52)
- Cmax(Day 1 and at Week 4)
- AUC t(Day 1 and at Week 4)
- Apparent Total Body Clearance of the Drug(At Week 4)
- Mean Change From Baseline of ECG Results - QRS Duration(From baseline up to week 52)
- Percentage of Participants With no Worsening of Steatohepatitis and ≥1 Stage Improvement in Liver Fibrosis Score at Week 52(From baseline up to week 52)
- Percentage of Participants With Improvement in Total NAS(From baseline up to week 52)
- Mean Change From Baseline in Liver Biochemistry(From baseline up to week 52)
- AUC (0-t)(Day 1 and at Week 4)
- Number of Participants With Treatment Related Safety Events(From baseline up to week 52)
- Mean Change From Baseline of ECG Results - QT Interval(From baseline up to week 52)
- Mean Change From Baseline of ECG Results - QTcF Interval(From baseline up to week 52)
- Percentage of Participants With Resolution of NASH With no Worsening of Liver Fibrosis(From baseline up to week 52)
- Mean Change From Baseline in Metabolic Parameters(From baseline up to week 52)