临床试验/NCT06016842

NCT06016842招募中3 期

A Phase III Randomised, Parallel-Group, Double-Blind, Placebo-Controlled, Two-Arm Study to Evaluate the Efficacy and Safety of Elafibranor 80 mg on Long-Term Clinical Outcomes in Adult Participants With Primary Biliary Cholangitis (PBC)

Ipsen366 个研究点分布在 15 个国家目标入组 276 人开始时间: 2023年8月31日最近更新: 2026年8月31日

适应症

干预措施

试验速览

阶段: 3 期
状态: 招募中
发起方: Ipsen
入组人数: 276
试验地点: 366
主要终点: Event-free survival

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

The participants of this study will have confirmed Primary Biliary Cholangitis (PBC) and cirrhosis (scarring of the liver).

PBC is a slowly progressive disease, characterised by damage to the bile ducts in the liver, leading to a build-up of bile acids which causes further damage.

The liver damage in PBC may lead to cirrhosis. PBC may also be associated with multiple symptoms. Many patients with PBC may require liver transplant or may die if the disease progresses and a liver transplant is not done.

This study will compare a daily dose of elafibranor (the study drug) to a daily dose of placebo (a dummy treatment) and will last up to 3.5 years for each participant.

The main aim of this study is to determine if elafibranor is better than placebo in preventing clinical outcome events showing disease worsening (including progression of disease leading to liver transplant or death).

This study will also study the safety of long-term treatment with elafibranor, as well as the impact on symptoms such as itching and tiredness.

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: Triple (Participant, 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

•Male or female participants must be ≥18 years of age at the time of signing the informed consent.
•Participants with a definite or probable diagnosis of primary biliary cholangitis (PBC)
•Participants with cirrhosis at SV
•Participants must be Child Pugh A or Child Pugh B.
•Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
•Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

排除标准

•History or presence of other concomitant liver disease including but not limited to:
•i) Primary sclerosing cholangitis (PSC).
•ii) Autoimmune hepatitis (AIH) by simplified Diagnostic Criteria of the International Autoimmune Hepatitis Group (IAIHG) ≥6, or if treated for an overlap of PBC with AIH, or if there is clinical suspicion and evidence of overlap AIH features, that cannot be explained alone by insufficient response to UDCA.
•iii) Positive hepatitis B surface antigen (HBsAg). Participants with negative HBsAg and positive hepatitis B core antibody (HBcAb) may be eligible if hepatitis B virus deoxyribonucleic acid (HBV DNA) is negative.
•iv) Hepatitis C virus (HCV) infection defined by positive anti-HCV antibody and positive HCV ribonucleic acid (RNA) (Note: Participants with positive anti-HCV antibody due to previously treated HCV infection, may be enrolled if a confirmatory HCV RNA is undetectable and sustained viral response has been documented).
•v) Alcohol-associated liver disease (ALD).
•vi) Nonalcoholic steatohepatitis (NASH).
•vii) Other chronic liver diseases, such as alpha-1 antitrypsin deficiency.
•History or presence of clinically significant hepatic decompensation, including:
•i) History of liver transplantation, current placement on a liver transplant list, current model for end-stage liver disease including (MELD) 3.0 score >12 due to hepatic impairment.
•ii) Evidence of complications of cirrhosis, including hepatic decompensation or evidence of significant portal hypertension complications including presence of uncontrolled ascites; history of variceal bleeding or related interventions (e.g. variceal banding, or transjugular intrahepatic portosystemic shunt placement); presence of hepatic encephalopathy Grade 2 or higher per West-Haven criteria; history or presence of spontaneous bacterial peritonitis. Note: participants with low-risk varices (Grade I) without history of bleeding or other treatment may be eligible to enrol.
•iii) Hepatorenal syndrome (HRS) (type I or II ). • vi) Hospitalisation for liver-related complication within 12 weeks prior to SV
•Known history of human immunodeficiency virus (HIV) infection or having a positive confirmatory test for HIV type 1 or
•Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget's disease).
•Evidence of any other unstable or untreated clinically significant immunological, endocrine, hematologic, gastrointestinal, neurological, or psychiatric disease as evaluated by the investigator; other clinically significant conditions that are not well controlled.
•Non-hepatic medical conditions that may diminish life expectancy to <2 years, including known cancers.
•History of hepatocellular carcinoma.
•Alpha-fetoprotein (AFP) >20 ng/mL with 4-phase liver computerised tomography (CT) or magnetic resonance imaging (MRI) imaging suggesting presence of hepatocellular carcinoma.
•Known malignancy or history of malignancy within the last 5 years. Participants with non-melanoma skin cancer, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
•Administration of the following medications is prohibited during the study, and prior to the study as per the timelines specified below: • i) 3 months prior to baseline: fibrates, seladelpar, glitazones, obeticholic acid, azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (parenteral and oral chronic administration only); 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 study or medical device study containing active substance within 30 days or 5 half-lives, whichever is longer, prior to the screening period.
•i) If the previous study was for an experimental therapy being studied for potential benefit in PBC, and the potential therapeutic agent was proven to have no beneficial effect in PBC and there are no safety concerns, the participant may enrol after 30 days or 5 half-lives from the last dose of the therapeutic agent, whichever is longer.ii) For therapeutic agents being studied for potential benefit in PBC for which it is still unclear if there may be a potential benefit, participants may enrol after 6 months from the last dose of the therapeutic agent.
•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. For participants with bundle branch block or other intraventricular conduction delay, a longer QTcF >480 msec would be exclusionary.
•Total bilirubin (TB) >5x ULN
•Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >5x ULN at SV1
•Creatinine phosphokinase (CPK) >2x ULN.
•Platelet count <50,000/μL
•International normalised ratio (INR) >1.8 in the absence of anticoagulant therapy.
•Estimated glomerular filtration rate (eGFR) <45 mL/min/1.73m2 per the Modification of Diet in Renal Disease (MDRD)-6 Study formula at SV
•Significant renal disease, including nephritic syndrome, chronic kidney disease (CKD) (defined as participants with evidence of significantly impaired kidney function or underlying kidney injury).
•For female participants: known current pregnancy, or has a positive serum pregnancy test, or is breastfeeding.
•Participants unwilling or unable to be abstinent from alcohol during the study.
•History of alcohol abuse, or other substance abuse within 1 year prior to SV
•Known hypersensitivity to elafibranor or to any of the excipients of the investigational product(s).
•Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.
•Any other condition that, in the opinion of the investigator, would interfere with study participation or completion, or would put the participant at risk, including a potential participant assessed as being at high risk of noncompliance with the study.
•Alkaline phosphatase (ALP) ≥10x ULN.
•Albumin <2.8 g/dL due to impaired hepatic function.

研究组 & 干预措施

Elafibranor 80 mg

Experimental

Participants will take 1 tablet of elafibranor 80 mg per day orally with a glass of water at approximately the same time each morning, with or without food.

干预措施: Elafibranor (Drug)

Placebo

Placebo Comparator

Participants will take 1 placebo tablet per day orally (matching the 80 mg elafibranor sized tablet) with a glass of water at approximately the same time each morning, with or without food.

干预措施: Matched 80 mg placebo (Other)

结局指标

主要结局

Event-free survival

时间窗: From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 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 experiencing Treatment Emergent Adverse Events (TEAEs), treatment-related TEAEs, Serious Adverse Events (SAEs), and Adverse Events of Special Interests (AESIs)(From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years))
Percentage of participants developing clinically significant changes in physical examination findings(From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years))
Percentage of participants developing clinically significant changes in vital signs(From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years))
Percentage of participants developing clinically significant changes in Electrocardiogram (ECG) readings.(From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years))
Percentage of participants with clinically significant changes in laboratory parameters (blood chemistry, hematology, coagulation and urinalysis)(From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years))
Change from baseline in Alkaline phosphatase (ALP)(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in Total Bilirubin (TB)(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with ALP≤ 1.67x ULN and TB≤ ULN(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with complete biochemical response(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with normalisation of TB and ALP(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with stabilisation in TB (i.e. no increase)(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with a response based on albumin normalisation(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in liver stiffness measurement (LSM)(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in PBC risk scores based in Global PBC Study Group (GLOBE) score(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in PBC risk scores based on United Kingdom (UK)-PBC score.(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with LSM ≥15 kPa(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change in serum levels of Aspartate aminotransferase (AST) compared to the baseline(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change in serum levels of ALT compared to the baseline(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change in serum levels of Gamma-glutamyl transferase (GGT) compared to the baseline(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in hepatic function: Conjugated bilirubin(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change in serum levels of Albumin compared to the baseline(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in hepatic function: international normalised ratio (INR)(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in hepatic function: fractionated ALP(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with no worsening of LSM(At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with ALP reduction of 40%(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with ALP <1.5x ULN, ALP decrease ≥15% and TB ≤ULN(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with ALP <1.5x ULN, ALP decrease ≥40% and TB ≤ULN(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with ALP <1.67x ULN, ALP decrease ≥15% and TB ≤ULN(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with ALP <3x ULN, AST <2x ULN and TB ≤1 mg/dL (Paris I)(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with ALP ≤1.5x ULN, AST ≤1.5x ULN and TB ≤1 mg/dL (Paris II criteria)(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with normalisation of abnormal TB(Assessed at Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with normalisation of abnormal TB and albumin (Rotterdam criteria)(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with reduction in TB to ≤0.6x ULN in participants with TB >0.6x ULN at baseline(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in lipid parameters: total cholesterol (TC)(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in lipid parameters: high density lipoprotein cholesterol (HDL-C)(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in lipid parameters: calculated very low density lipoprotein cholesterol (VLDL-C)(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in lipid parameters: low density lipoprotein cholesterol (LDL-C)(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in lipid parameters: triglycerides (TG)(At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with a response in PBC Worst Itch NRS score(Through 6 months up to end of treatment (maximum duration of 3.5 years))
Percentage of participants with a response in PBC Worst Itch NRS(Assessed through 6 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in 5D-Itch scale(Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in Patient Global Impression of Severity (PGI-S)(Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years))
Patient Global Impression of Change (PGI-C)(Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form 7a(Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in the Epworth Sleepiness Scale (ESS)(Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in PBC-40 score(Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in PBC Worst Itch Numeric Rating Scale (NRS) score(Assessed through 6 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in EuroQol 5-dimensional 5-level questionnaire (EQ-5D-5L)(Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years))
Change from baseline in Work Productivity and Activity Impairment General Health (WPAI-GH)(Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years))
Time to the first occurrence of each of individual adjudicated clinical outcome events(From baseline until 4 weeks after the end of treatment)
Area under the plasma concentration-time curve from time 0 to 24 hours: AUC0-24(At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours))
Maximum (peak) plasma drug concentration: Cmax(At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours))
Time to reach maximum (peak) plasma concentration following drug administration): Tmax(At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours))
Apparent clearance of drug from plasma (CL)(At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours))
Apparent volume of distribution (VZ)(At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours))
Change from baseline in model for end-stage liver disease (MELD) 3.0 score(From screening until end of treatment (maximum duration of 3.5 years))
Change from baseline in Child Pugh grade(From screening until end of treatment (maximum duration of 3.5 years))

研究者

发起方

Ipsen

申办方类型

Industry

责任方

Sponsor

研究点 (366)

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