NCT03124108已完成2 期
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Elafibranor at Doses of 80 mg and 120mg After 12 Weeks of Treatment in Patients With Primary Biliary Cholangitis and Inadequate Response to Ursodeoxycholic Acid
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Genfit
- 入组人数
- 45
- 试验地点
- 24
- 主要终点
- Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) Levels at Week 12 (Endpoint)
研究概览
简要总结
The primary objective of the study is to compare the effect of daily oral administration of elafibranor 80mg and 120 mg on change in serum alkaline phosphatase (ALP) to that of placebo in patients with PBC and inadequate response to Ursodeoxycholic acid (UDCA).
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must have provided written informed consent
- •Definite or probable PBC diagnosis as demonstrated by the presence of at least 2 of the following 3 diagnostic factors:
- •History of elevated ALP levels for at least 6 months prior to Day 0 (randomization visit)
- •Positive Anti-Mitochondrial Antibodies (AMA) titers (> 1/40 on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies
- •Liver biopsy consistent with PBC
- •ALP >= 1.67x upper limit of normal (ULN)
- •Taking UDCA for at least 12 months (stable dose for ≥ 6 months) prior to screening visit
- •Contraception: Females participating in this study must be of non-childbearing potential or must be using highly efficient contraception for the full duration of the study and for 1 month after the end of treatment.
排除标准
- •History or presence of other concomitant liver diseases
- •Screening creatine phosphokinase (CPK) > upper limits of normal (ULN)
- •Screening alanine transaminase (ALT) or aspartate aminotransferase (AST) > 5 ULN
- •Screening total bilirubin > 2 ULN
- •Screening serum creatinine > 1.5 mg/dl
- •Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as patients with markers of kidney damage or estimated glomerular filtration rate [eGFR] of less than 60 mL/min/1.73 m^2).
- •Patients with moderate or severe hepatic impairment (defined as Child-Pugh B/C)
- •Platelet count <150 X 10^3/microliter
- •Albumin <3.5 g/dL
- •Presence of clinical complications of PBC or clinically significant hepatic decompensation
- •If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
- •Known history of human immunodeficiency virus (HIV) infection
- •Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease)
研究组 & 干预措施
Placebo
Placebo Comparator
Study subjects will take two tablets per day orally before breakfast with a glass of water each morning
干预措施: Placebo (Drug)
Elafibranor 80 mg
Active Comparator
Study subjects will take two tablets per day orally before breakfast with a glass of water each morning
干预措施: Elafibranor 80 mg (Drug)
Elafibranor 120 mg
Active Comparator
Study subjects will take two tablets per day orally before breakfast with a glass of water each morning
干预措施: Elafibranor 120 mg (Drug)
结局指标
主要结局
Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) Levels at Week 12 (Endpoint)
时间窗: Baseline, Week 12 (Endpoint)
Relative change from baseline is in serum ALP levels at Week 12 (endpoint) were reported. Relative change from baseline is defined as percentage (%) change from baseline to endpoint.
次要结局
- Percentage of Participants With Response Based on Toronto II Risk Score at Endpoint(At Week 12 (Endpoint))
- Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Endpoint(At Week 12 (Endpoint))
- Change From Baseline in Aspartate Aminotransferase (AST) Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Albumin Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Low-density Lipoprotein (LDL) Cholesterol Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in High-density Lipoprotein (HDL) Cholesterol Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Triglycerides Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Transforming Growth Factor Beta Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Plasminogen Activator Inhibitor-1 Antigen (AG) Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Percentage of Participants With Response Defined by Composite Risk Scores (ALP < 2 * Upper Limit of Normal at Endpoint, Total Bilirubin Within Normal Limits at Endpoint, and > 40% ALP Reduction From Baseline to Endpoint)(Up to Week 12 (Endpoint))
- Change From Baseline in Conjugated Bilirubin Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Total Conjugated Bile Acid Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Percentage of Participants With Response Based on PARIS I Risk Score at Endpoint(At Week 12 (Endpoint))
- Percentage of Participants With Response Based on PARIS II Risk Score at Endpoint(At Week 12 (Endpoint))
- Percentage of Participants With Response Based on Toronto I Risk Score at Endpoint(At Week 12 (Endpoint))
- Percentage of Participants With Response Defined by Composite Risk Scores (ALP< 1.67 * Upper Limit of Normal [ULN] at Endpoint, Total Bilirubin [BIL] Within Normal Limits at Endpoint, and Greater Than [>] 15% ALP Reduction From Baseline to Endpoint)(Up to Week 12 (Endpoint))
- Percentage of Participants With Response Defined by 10, 20 and 40 Percent Reduction in Alkaline Phosphatase(At Week 12 (Endpoint))
- Change From Baseline in Alanine Aminotransferase (ALT) Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Gamma-glutamyl Transferase (GGT) Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in 7 Alpha-hydroxy-4-cholesten-3-one Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Fibroblast Growth Factor-19 Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Immunoglobulin M (IgM) Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Cytokeratin-18 Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Autotaxin Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events(Up to Week 12)
- Median Percentage Risk as Assessed by United Kingdom-Primary Biliary Cholangitis (UK-PBC) Risk Total Score at Endpoint(At Week 12 (Endpoint))
- Percentage of Participants With Response Defined by Normalized Bilirubin (BIL) at Endpoint(At Week 12 (Endpoint))
- Percentage of Participants With Response Defined by Normalized Albumin (ALB) Levels at Endpoint(At Week 12 (Endpoint))
- Change From Baseline in 5 Prime (') Nucleotidase Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Total Bilirubin (BIL) Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Total Free Bile Acid Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Total Bile Acid Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Tumor Necrosis Factor Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Cholesterol Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Haptoglobin Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Primary Biliary Cholangitis -40 (PBC-40) Quality of Life (QoL) Questionnaire Scores(Baseline, Week 12 (Endpoint))
- Change From Baseline in Interleukin 6 Levels at Endpoint(Baseline, Week 12 (Endpoint))
- C-reactive Protein Level at Endpoint(Week 12 (Endpoint))
- Change From Baseline in Fibrinogen Levels at Endpoint(Baseline, Week 12 (Endpoint))
- Change From Baseline in Pruritus as Assessed by Visual Analogue Scale (VAS) Total Score(Baseline, Week 12 (Endpoint))
- Change From Baseline in 5D-Itch Scale Total Score(Baseline, Week 12 (Endpoint))
研究者
研究点 (24)
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