A Phase III, Multicentre, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Elafibranor in Adult Participants With Primary Sclerosing Cholangitis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Ipsen
- 入组人数
- 350
- 试验地点
- 13
- 主要终点
- Event-Free Survival
研究概览
简要总结
The purpose of this study is to find out how well and safely elafibranor works compared to placebo in adult participants with Primary sclerosing cholangitis (PSC). PSC is a rare disease that causes inflammation and scarring of the bile ducts in the liver. Over time, this can lead to liver damage and serious health problems, including the need for a liver transplant and death.
In this study, about 350 participants with large duct PSC will take part. Participants will be randomized to receive either elafibranor 120 mg once daily or a placebo (a tablet with no active medicine). The study includes a screening period, an treatment period, and a post-treatment safety follow-up.
During the study, participants will undergo routine clinical assessments, laboratory testing, imaging evaluations, and complete patient-reassessments to evaluate liver disease progression, symptoms, quality of life and safety.
Following the end of treatment, participants will complete a safety follow-up period at approximately four weeks. Participants may withdraw from the study at any time. Each participant may be in the study for several years, as the treatment period will continue until the study reaches enough health events among participants, which is expected to take about 5 years.
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
- Double (Participant, Investigator)
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
- •Adults participants aged 18 years or older
- •Confirmed diagnosis of primary sclerosing cholangitis based on standard clinical, biochemical, and imaging criteria
- •Compensated liver disease at screening
- •Stable background therapy, where applicable prior to study entry
- •Women of childbearing potential have to apply during the entire duration of the study a highly effective method of birth control
- •Ability to provide written informed consent and comply with study procedures.
排除标准
- •- History or presence of other concomitant chronic liver disease
- •- History of hepatic decompensation, including: i) History of liver transplantation, current MELD 3.0 score ≥12 due to hepatic impairment.
- •ii) Evidence of complications of cirrhosis
- •Participants with cirrhosis who are also classified as Child-Pugh B or C based on the Child Pugh score.
- •History of biliary intervention within 60 days prior to the screening period, and/or presence of percutaneous drain or bile duct stent at SV.
- •History of bacterial cholangitis, and/or participant on antibiotics for prophylaxis of recurrent cholangitis within 60 days prior to the SV.
- •History or any current suspicion of cholangiocarcinoma or hepatocellular carcinoma
- •Known malignancy or history of malignancy within the last 5 years, with the exception of local, successfully treated basal cell carcinoma or in-situ carcinoma of the uterine cervix.
- •Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget's disease).
- •Administration of the following medications are prohibited as specified below:
- •i) 3 months prior to baseline: norucholic acid, fibrates, seladelpar and glitazones.
- •ii) 3 months prior to baseline: cyclosporine, mycophenolate, pentoxifylline, and chronic systemic corticosteroids (except as part of management of IBD at an ongoing stable dose); potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazid, or nitrofurantoin).
- •Participants who are currently participating in, plan to participate in, or have participated in an investigational drug or medical device study containing active substance within 30 days or five half-lives, whichever is longer, prior to the SV. - Participants with previous exposure to elafibranor.
- •Electrocardiogram (ECG) with QT interval corrected by Fridericia's formula (QTcF) >450 msec in males or QTcF >470 msec in females for participants without bundle branch block.
- •Significant renal disease,
- •For female participants: known pregnancy, or has a positive serum pregnancy test, or lactating.
- •Regular alcohol intake in excess of the recommended limit of 2 standard drinks per day for men or 1 standard drink per day for women
- •History of alcohol abuse, or other substance abuse within 1 year prior to SV.
- •Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that contraindicates participation in the study.
- •Mental instability or incompetence
- •Participant has or is known to have tested positive for human immunodeficiency virus (HIV) type 1 or 2 at SV.
- •Medical conditions that may diminish life expectancy to <2 years.
研究组 & 干预措施
Placebo
Participants will take 1 placebo tablet orally once daily
干预措施: Placebo (Other)
Elafibranor 120 mg
Participants will take 1 tablet of elafibranor 120 mg orally once daily
干预措施: Elafibranor (Drug)
结局指标
主要结局
Event-Free Survival
时间窗: From baseline until the end of treatment (estimated up to 5 years)
Event-free survival is defined as the time from randomisation to either adjudicated disease progression or death, whichever occurs first.
次要结局
- Percentage of participants with ALP level within the pre-defined level(From baseline to Week 48)
- Change from baseline in severity of a patient-reported cholestatic symptom: Pruritus(From baseline to Week 24)
- Change from baseline in severity of a patient-reported cholestatic symptom: Fatigue(From baseline to Week 48)
- Percentage of participants experiencing treatment-emergent adverse events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interests (AESIs)(From baseline until the end of treatment (estimated up to 5 years))
- Percentage of participants developing clinically significant changes in physical examination findings(From baseline until the end of treatment (estimated up to 5 years))
- Percentage of participants developing clinically significant changes in vital signs(From baseline until the end of treatment (estimated up to 5 years))
- Percentage of participants developing clinically significant changes in Electrocardiogram (ECG) readings.(From baseline until the end of treatment (estimated up to 5 years))
- Percentage of participants with clinically significant changes in laboratory parameters (blood chemistry, hematology, coagulation and urinalysis)(From baseline until the end of treatment (estimated up to 5 years))
- Percentage of participants developing cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC), or colorectal cancer (CRC)(From baseline until the end of treatment (estimated up to 5 years))