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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT06016842
Registration number
NCT06016842
Ethics application status
Date submitted
22/08/2023
Date registered
30/08/2023
Titles & IDs
Public title
A Long-Term Study of Elafibranor in Adult Participants With Primary Biliary Cholangitis
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Scientific title
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)
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Secondary ID [1]
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2023-505251-43-00
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Secondary ID [2]
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CLIN-60190-454
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Universal Trial Number (UTN)
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Trial acronym
ELFIDENCE
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Primary Biliary Cholangitis (PBC)
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Condition category
Condition code
Oral and Gastrointestinal
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Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
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Infection
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0
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Other infectious diseases
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Elafibranor
Other interventions - Matched 80 mg placebo
Experimental: Elafibranor 80 mg - 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.
Placebo comparator: 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.
Treatment: Drugs: Elafibranor
Duration: up to an estimated 42-month (3.5-year) double-blind treatment period during which elafibranor 80 mg tablet will be administered once daily
Other interventions: Matched 80 mg placebo
Duration: up to an estimated 42-month (3.5-year) double-blind treatment period during which matching placebo tablet will be administered once daily
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Intervention code [1]
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Treatment: Drugs
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Intervention code [2]
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Other interventions
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Event-free survival
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Assessment method [1]
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Event-free survival is defined as the time from randomisation to either adjudicated disease progression or death, whichever occurs first.
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Timepoint [1]
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From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)
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Secondary outcome [1]
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Percentage of participants experiencing Treatment Emergent Adverse Events (TEAEs), treatment-related TEAEs, Serious Adverse Events (SAEs), and Adverse Events of Special Interests (AESIs)
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Assessment method [1]
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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.
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Timepoint [1]
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From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)
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Secondary outcome [2]
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Percentage of participants developing clinically significant changes in physical examination findings
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Assessment method [2]
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Complete physical examination at screening and targeted examination at all other clinical visit timepoints.
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Timepoint [2]
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From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)
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Secondary outcome [3]
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Percentage of participants developing clinically significant changes in vital signs
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Assessment method [3]
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Percentage of participants with clinically significant changes in Vital Signs will be reported. The clinical significance will be graded by the investigator.
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Timepoint [3]
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From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)
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Secondary outcome [4]
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Percentage of participants developing clinically significant changes in Electrocardiogram (ECG) readings.
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Assessment method [4]
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Percentage of participants with clinically significant changes in ECG readings will be reported. The clinical significance will be graded by the investigator.
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Timepoint [4]
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From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)
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Secondary outcome [5]
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Percentage of participants with clinically significant changes in laboratory parameters (blood chemistry, hematology, coagulation and urinalysis)
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Assessment method [5]
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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.
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Timepoint [5]
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From baseline until 4 weeks after the end of treatment (maximum duration of 3.5 years)
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Secondary outcome [6]
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Change from baseline in Alkaline phosphatase (ALP)
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Assessment method [6]
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Timepoint [6]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [7]
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Change from baseline in Total Bilirubin (TB)
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Assessment method [7]
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0
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Timepoint [7]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [8]
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Percentage of participants with ALP= 1.67x ULN and TB= ULN
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Assessment method [8]
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Timepoint [8]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [9]
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Percentage of participants with complete biochemical response
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Assessment method [9]
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Defined as normal levels of TB, ALP, transaminases, albumin, and International normalised ratio (INR)
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Timepoint [9]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
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Secondary outcome [10]
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Percentage of participants with normalisation of TB and ALP
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Assessment method [10]
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Defined as TB\< Upper Limit Normal (ULN) and ALP\< ULN
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Timepoint [10]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [11]
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Percentage of participants with stabilisation in TB (i.e. no increase)
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Assessment method [11]
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Defined as TB\< 1x ULN or increase from baseline \<0.1x ULN
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Timepoint [11]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [12]
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Percentage of participants with a response based on albumin normalisation
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Assessment method [12]
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Timepoint [12]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [13]
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Change from baseline in liver stiffness measurement (LSM)
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Assessment method [13]
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Assessed by vibration-controlled transient elastography (VCTE) using Fibroscan® on the day of the visit.
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Timepoint [13]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [14]
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Change from baseline in PBC risk scores based in Global PBC Study Group (GLOBE) score
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Assessment method [14]
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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.
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Timepoint [14]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
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Secondary outcome [15]
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Change from baseline in PBC risk scores based on United Kingdom (UK)-PBC score.
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Assessment method [15]
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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.
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Timepoint [15]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [16]
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Percentage of participants with LSM =15 kPa
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Assessment method [16]
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Assessed by VCTE using Fibroscan®
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Timepoint [16]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
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Secondary outcome [17]
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Change in serum levels of Aspartate aminotransferase (AST) compared to the baseline
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Assessment method [17]
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Timepoint [17]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [18]
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Change in serum levels of ALT compared to the baseline
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Assessment method [18]
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Timepoint [18]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [19]
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Change in serum levels of Gamma-glutamyl transferase (GGT) compared to the baseline
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Assessment method [19]
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0
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Timepoint [19]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [20]
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Change from baseline in hepatic function: Conjugated bilirubin
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Assessment method [20]
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0
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Timepoint [20]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [21]
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Change in serum levels of Albumin compared to the baseline
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Assessment method [21]
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0
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Timepoint [21]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [22]
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Change from baseline in hepatic function: international normalised ratio (INR)
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Assessment method [22]
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0
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Timepoint [22]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [23]
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Change from baseline in hepatic function: fractionated ALP
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Assessment method [23]
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0
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Timepoint [23]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [24]
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Percentage of participants with no worsening of LSM
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Assessment method [24]
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Assessed by VCTE using Fibroscan® defined as no increase \>2kPa from baseline
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Timepoint [24]
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At Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [25]
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Percentage of participants with ALP reduction of 40%
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Assessment method [25]
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Timepoint [25]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [26]
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Percentage of participants with ALP <1.5x ULN, ALP decrease =15% and TB =ULN
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Assessment method [26]
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0
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Timepoint [26]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [27]
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Percentage of participants with ALP <1.5x ULN, ALP decrease =40% and TB =ULN
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Assessment method [27]
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Timepoint [27]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [28]
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0
Percentage of participants with ALP <1.67x ULN, ALP decrease =15% and TB =ULN
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Assessment method [28]
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0
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Timepoint [28]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [29]
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Percentage of participants with ALP <3x ULN, AST <2x ULN and TB =1 mg/dL (Paris I)
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Assessment method [29]
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0
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Timepoint [29]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [30]
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0
Percentage of participants with ALP =1.5x ULN, AST =1.5x ULN and TB =1 mg/dL (Paris II criteria)
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Assessment method [30]
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0
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Timepoint [30]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [31]
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Percentage of participants with normalisation of abnormal TB
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Assessment method [31]
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0
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Timepoint [31]
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Assessed at Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [32]
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Percentage of participants with normalisation of abnormal TB and albumin (Rotterdam criteria)
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Assessment method [32]
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0
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Timepoint [32]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [33]
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Percentage of participants with reduction in TB to =0.6x ULN in participants with TB >0.6x ULN at baseline
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Assessment method [33]
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0
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Timepoint [33]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [34]
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Change from baseline in lipid parameters: total cholesterol (TC)
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Assessment method [34]
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0
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Timepoint [34]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [35]
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Change from baseline in lipid parameters: high density lipoprotein cholesterol (HDL-C)
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Assessment method [35]
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0
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Timepoint [35]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [36]
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Change from baseline in lipid parameters: calculated very low density lipoprotein cholesterol (VLDL-C)
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Assessment method [36]
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0
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Timepoint [36]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
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Secondary outcome [37]
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Change from baseline in lipid parameters: low density lipoprotein cholesterol (LDL-C)
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Assessment method [37]
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0
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Timepoint [37]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [38]
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Change from baseline in lipid parameters: triglycerides (TG)
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Assessment method [38]
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0
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Timepoint [38]
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At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [39]
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Percentage of participants with a response in PBC Worst Itch NRS score
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Assessment method [39]
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Defined as =2-point reduction from baseline NRS in participants with a baseline NRS =4
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Timepoint [39]
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Through 6 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [40]
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Percentage of participants with a response in PBC Worst Itch NRS
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Assessment method [40]
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Defined as =3-point reduction from baseline NRS in participants with a baseline NRS =4
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Timepoint [40]
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Assessed through 6 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [41]
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Change from baseline in 5D-Itch scale
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Assessment method [41]
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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.
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Timepoint [41]
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Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [42]
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0
Change from baseline in Patient Global Impression of Severity (PGI-S)
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Assessment method [42]
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A 1-item, 5-point scale designed to assess the participant's impression of disease severity
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Timepoint [42]
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Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [43]
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Patient Global Impression of Change (PGI-C)
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Assessment method [43]
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A 1-item, 5-point scale designed to assess the participant's impression of change in disease severity since the baseline visit
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Timepoint [43]
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Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [44]
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Change from baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form 7a
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Assessment method [44]
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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.
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Timepoint [44]
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Assessed at every 6 months up to end of treatment (maximum duration of 7 years)
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Secondary outcome [45]
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Change from baseline in the Epworth Sleepiness Scale (ESS)
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Assessment method [45]
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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).
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Timepoint [45]
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Assessed at every 6 months up to end of treatment (maximum duration of 7 years)
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Secondary outcome [46]
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Change from baseline in PBC-40 score
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Assessment method [46]
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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.
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Timepoint [46]
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0
Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [47]
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0
Change from baseline in PBC Worst Itch Numeric Rating Scale (NRS) score
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Assessment method [47]
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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
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Timepoint [47]
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0
Assessed through 6 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [48]
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0
Change from baseline in EuroQol 5-dimensional 5-level questionnaire (EQ-5D-5L)
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Assessment method [48]
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0
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).
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Timepoint [48]
0
0
Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [49]
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0
Change from baseline in Work Productivity and Activity Impairment General Health (WPAI-GH)
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Assessment method [49]
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0
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).
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Timepoint [49]
0
0
Assessed at every 6 months up to end of treatment (maximum duration of 3.5 years)
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Secondary outcome [50]
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0
Time to the first occurrence of each of individual adjudicated clinical outcome events
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Assessment method [50]
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Among: • All-cause mortality • Liver-related mortality • Liver transplant • MELD-3.0 score =15 in participants with baseline MELD score =12 • Liver decompensation • Occurrence of hepatocellular carcinoma
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Timepoint [50]
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0
From baseline until 4 weeks after the end of treatment
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Secondary outcome [51]
0
0
Area under the plasma concentration-time curve from time 0 to 24 hours: AUC0-24
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Assessment method [51]
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0
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Timepoint [51]
0
0
At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
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Secondary outcome [52]
0
0
Maximum (peak) plasma drug concentration: Cmax
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Assessment method [52]
0
0
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Timepoint [52]
0
0
At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
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Secondary outcome [53]
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0
Time to reach maximum (peak) plasma concentration following drug administration): Tmax
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Assessment method [53]
0
0
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Timepoint [53]
0
0
At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
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Secondary outcome [54]
0
0
Apparent clearance of drug from plasma (CL)
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Assessment method [54]
0
0
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Timepoint [54]
0
0
At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
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Secondary outcome [55]
0
0
Apparent volume of distribution (VZ)
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Assessment method [55]
0
0
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Timepoint [55]
0
0
At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
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Secondary outcome [56]
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0
Change from baseline in model for end-stage liver disease (MELD) 3.0 score
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Assessment method [56]
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0
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.
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Timepoint [56]
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0
From screening until end of treatment (maximum duration of 3.5 years)
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Secondary outcome [57]
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0
Change from baseline in Child Pugh grade
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Assessment method [57]
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0
Child Pugh grade is calculated using bilirubin, albumin, INR, ascites and encephalopathy.
A high grade is indicative of worse liver disease.
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Timepoint [57]
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0
From screening until end of treatment (maximum duration of 3.5 years)
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Eligibility
Key inclusion criteria
Inclusion Criteria :
* 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 SV1. • 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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
Exclusion Criteria :
* 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 SV1.
* Known history of human immunodeficiency virus (HIV) infection or having a positive confirmatory test for HIV type 1 or 2.
* 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, with the exception of local, successfully treated basal cell carcinoma or in-situ carcinoma of the uterine cervix.
* 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 screening period: 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 a-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 SV1.
* 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.
* Regular alcohol intake in excess of the recommended limit of 1 standard drink per day for men or women.
* History of alcohol abuse, or other substance abuse within 1 year prior to SV1.
* 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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people assessing the outcomes
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
31/08/2023
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/05/2029
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Actual
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Sample size
Target
276
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
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St George Hospital - Sydney
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Westmead Hospital - Westmead
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- Sydney
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- Westmead
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Zaragoza
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Ipsen
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Address
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/study/NCT06016842
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Ipsen Medical Director
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Ipsen
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Contact person for public queries
Name
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Ipsen Clinical Study Enquiries
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[email protected]
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
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What data in particular will be shared?
Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.
Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.
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When will data be available (start and end dates)?
Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
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Available to whom?
Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
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Available for what types of analyses?
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How or where can data be obtained?
IPD available at link: https://vivli.org/members/ourmembers/
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT06016842