A Long-Term Study of Elafibranor in Adult Participants With Primary Biliary Cholangitis
- Conditions
- Primary Biliary Cholangitis (PBC)
- Interventions
- Other: Matched 80 mg placebo
- Registration Number
- NCT06016842
- Lead Sponsor
- Ipsen
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 276
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Matched 80 mg placebo Participants will take 1 placebo tablet per day orally (matching the 80 mg elafibranor sized tablet) before breakfast with a glass of water at approximately the same time each morning. Elafibranor 80 mg Elafibranor Participants will take 1 tablet of elafibranor 80 mg per day orally before breakfast with a glass of water at approximately the same time each morning.
- Primary Outcome Measures
Name Time Method Event-free survival 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.
- Secondary Outcome Measures
Name Time Method 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) An Adverse event (AE) is any untoward medical occurrence, temporally associated with the use of study intervention, whether or not related to the study intervention. AESIs are AEs that may not be serious but are of special importance to a particular drug or class of drugs.
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) Complete physical examination at screening and targeted examination at all other clinical visit timepoints.
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 with clinically significant changes in Vital Signs will be reported. The clinical significance will be graded by the investigator.
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 ECG readings will be reported. The clinical significance will be graded by the investigator.
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) Percentage of participants with clinically significant change in laboratory parameters (blood chemistry, hematology and coagulation) will be reported. The clinical significance will be graded by the investigator.
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) Defined as normal levels of TB, ALP, transaminases, albumin, and International normalised ratio (INR)
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) Defined as TB\< Upper Limit Normal (ULN) and ALP\< ULN
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) Defined as TB\< 1x ULN or increase from baseline \<0.1x ULN
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) Assessed by vibration-controlled transient elastography (VCTE) using Fibroscan® on the day of the visit.
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) The GLOBE score is a validated risk assessment tool providing an estimate of transplant-free survival for patients with PBC. It was developed by the Global PBC Study Group using Cox regression model on over 4,000 patients with PBC. Lower GLOBE score predicts lower risk. It is calculated from the following equation:
GLOBE score = (0.044378 \* age + 0.93982 \* LN(total bilirubin/ULN) +(0.335648 \* LN(alkaline phosphatase/ULN)) - 2.266708 \* albumin /LLN -0.002581 \* platelet count per 109/L) + 1.216865
GLOBE scoring system, which calculation is based on serum values of bilirubin, ALP, albumin and platelet count after 1 year of treatment and age at baseline. A high number is indicative of a worse score.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) PBC risk score developed by United Kingdom (UK)-PBC Consortium is a scoring system and the calculation is based on laboratory test measurements and upper limits of normal (ULN) for the total bilirubin (BIL12); alanine transaminase or aspartate transaminase (TA12), and alkaline phosphatase (ALP12) after at least 12 months of UDCA, and the laboratory test measurements and lower limits of normal (LLN) for the serum albumin and platelet count in the same timeframe. A high number is indicative of a worse score.
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) Assessed by VCTE using Fibroscan®
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) Assessed by VCTE using Fibroscan® defined as no increase \>2kPa from baseline
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) Defined as ≥2-point reduction from baseline NRS in participants with a baseline NRS ≥4
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) Defined as ≥3-point reduction from baseline NRS in participants with a baseline NRS ≥4
Change from baseline in 5D-Itch scale Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years) Questionnaire that assesses symptoms in terms of 5 domains: degree, duration, direction, disability and distribution. Participants rate their symptoms over the preceding 2-week period on a 1 to 5 scale, with 5 being the most affected.
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) A 1-item, 5-point scale designed to assess the participant's impression of disease severity
Patient Global Impression of Change (PGI-C) Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years) A 1-item, 5-point scale designed to assess the participant's impression of change in disease severity since the baseline visit
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) Consists of 7 items that measure both the experience of fatigue and the interference of fatigue on daily activities over the past week. Response options are on a 5-point Likert scale, ranging from 1 to 5. Scores can range from 7 to 35, with higher scores indicating greater fatigue.
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) Self-administered questionnaire that consists of 8 questions asking to rate how likely it is to fall asleep in different situations commonly encountered in daily life (each question can be scored from 0 to 3 points; '0' indicates no sleepiness, '3' indicates significant sleepiness). It provides a total score which has been shown to relate to the participant's level of daytime sleepiness (total score range 0-24 points).
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) Questionnaire that measures absenteeism, presenteeism as well as the impairments in unpaid activity because of health problem during the past seven days. It consists of 6 questions: 1=currently employed; 2=hours missed because of health problems; 3=hours missed because of other reasons; 4=hours actually worked; 5=degree health affected productivity while working (using a 0 to 10 Visual Analogue Scale (VAS)); 6=degree health affected productivity in regular unpaid activities (VAS).
Time to the first occurrence of each of individual adjudicated clinical outcome events From baseline until 4 weeks after the end of treatment Among: • All-cause mortality • Liver-related mortality • Liver transplant • MELD-3.0 score ≥15 in participants with baseline MELD score ≤12 • Liver decompensation
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) 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) The MELD 3.0 score is calculated from parameters (sex, creatinine, bilirubin, INR, sodium and albumin) where a high score indicates a greater risk of needing a liver transplant.
Change from baseline in Child Pugh grade From screening until end of treatment (maximum duration of 3.5 years) Child Pugh grade is calculated using bilirubin, albumin, INR, ascites and encephalopathy.
A high grade is indicative of worse liver disease.Change from baseline in PBC-40 score Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years) 40-item questionnaire that assesses symptoms across 6 domains: fatigue, emotional and social, cognitive function, general symptoms and itch. Participants respond on a verbal response scale, depending on the section options range from 'never' / 'not at all' / 'strongly disagree' to 'always' / 'very much' / 'strongly agree'. Six items (3/3 in the itch domain, 2/10 in the social domain, and 1/7 in the general symptoms domain) also include a 'does not apply' option. A score for each domain is provided (but a total score is not calculated), with each verbal response scale correlating to a score of 1 to 5 per item (0 to 5 on items with a 'does not apply' option) with 5 being the most affected (greatest burden). The PBC-40 has a 4-week recall period.
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) Self-administered patient-reported outcome questionnaire that measures itch intensity. It asks participants to rate the intensity of their Worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (Worst Itch imaginable): - once daily (24-hour recall period) using the eDiary during the screening and initial 2 years of the study, - at the clinic visits (7-day recall period), from Year 3 onwards
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) Self-administered standardised questionnaire that assesses the 5-dimensions of mobility, self-care, usual activities, pain/discomfort, anxiety/depression descriptively (each dimension has 5 levels) and the overall health state via an EQ Visual Analogue Scale (VAS).
Maximum (peak) plasma drug concentration: Cmax At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
Trial Locations
- Locations (149)
Centro de Estudios Clinicos e Investigaciones Medicas (CECIM)
🇨🇱Santiago, Chile
Arizona Liver Health
🇺🇸Tucson, Arizona, United States
Arkansas Diagnostic Center, PA
🇺🇸Little Rock, Arkansas, United States
Southern California Research Center
🇺🇸Coronado, California, United States
Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
GastroIntestinal BioSciences
🇺🇸Los Angeles, California, United States
University of California Los Angeles
🇺🇸Los Angeles, California, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Peak Gastroenterology Associates
🇺🇸Colorado Springs, Colorado, United States
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