xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06016842</url>
    </required_header>
    <id_info>
      <org_study_id>CLIN-60190-454</org_study_id>
      <secondary_id>2023-505251-43-00</secondary_id>
      <nct_id>NCT06016842</nct_id>
    </id_info>
    <brief_title>A Long-Term Study of Elafibranor in Adult Participants With Primary Biliary Cholangitis</brief_title>
    <acronym>ELFIDENCE</acronym>
    <official_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)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Ipsen</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Ipsen</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The participants of this study will have confirmed Primary Biliary Cholangitis (PBC).&#xD;
  &#xD;
        Participants will also have inadequate response or intolerance to ursodeoxycholic acid (UDCA)&#xD;
        a drug used to treat PBC.&#xD;
  &#xD;
        PBC is a disease that progresses slowly. It causes damage to the bile ducts in the liver,&#xD;
        leading to a build-up of bile acids which causes further damage.&#xD;
  &#xD;
        The liver damage in PBC may lead to scarring (cirrhosis). PBC may also be associated with&#xD;
        multiple symptoms. Many people with PBC may require liver transplant or may die if the&#xD;
        disease progresses and a liver transplant is not done.&#xD;
  &#xD;
        This study will compare a daily dose of elafibranor (the study drug) to a daily dose of&#xD;
        placebo (a dummy treatment). Each participant will be in the study up to about 7 years.&#xD;
  &#xD;
        The main aim of this study is to determine if elafibranor is better than placebo in&#xD;
        preventing clinical outcome events showing disease worsening (including progression of&#xD;
        disease leading to liver transplant or death).&#xD;
  &#xD;
        This study will also study the safety of long-term treatment with elafibranor, as well as the&#xD;
        impact on symptoms such as itching and tiredness.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">October 18, 2030</completion_date>
    <primary_completion_date type="Anticipated">October 18, 2030</primary_completion_date>
    <phase>Phase 3</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Event-free survival</measure>
      <time_frame>From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)</time_frame>
      <description>Event-free survival is defined as the time from start of treatment to either adjucated disease progression or death, whichever occurs first.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants experiencing Treatment Emergent Adverse Events (TEAEs), treatment-related TEAEs, Serious Adverse Events (SAEs), and Adverse Events of Special Interests (AESIs)</measure>
      <time_frame>From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants developing clinically significant changes in physical examination findings</measure>
      <time_frame>From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)</time_frame>
      <description>Complete physical examination at screening and targeted examination at all other clinical visit timepoints.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants developing clinically significant changes in vital signs</measure>
      <time_frame>From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)</time_frame>
      <description>Percentage of participants with clinically significant changes in Vital Signs will be reported. The clinical significance will be graded by the investigator.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants developing clinically significant changes in Electrocardiogram (ECG) readings.</measure>
      <time_frame>From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)</time_frame>
      <description>Percentage of participants with clinically significant changes in ECG readings will be reported. The clinical significance will be graded by the investigator.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with clinically significant changes in laboratory parameters (blood chemistry, hematology, coagulation and urinalysis)</measure>
      <time_frame>From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in Alkaline phosphatase (ALP)</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in Total Bilirubin (TB)</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with ALP≤ 1.67x ULN and TB≤ ULN</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with complete biochemical response</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>Defined as normal levels of TB, ALP, transaminases, albumin, and International normalised ratio (INR)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with normalisation of TB and ALP</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>Defined as TB&lt; Upper Limit Normal (ULN) and ALP&lt; ULN</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with stabilisation in TB (i.e. no increase)</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>Defined as TB&lt; 1x ULN or increase from baseline &lt;0.1x ULN</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with a response based on albumin normalisation</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in liver stiffness measurement (LSM)</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>Assessed by vibration-controlled transient elastography (VCTE) using Fibroscan® on the day of the visit.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in PBC risk scores based in Global PBC Study Group (GLOBE) score</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>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:&#xD;
  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&#xD;
  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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in PBC risk scores based on United Kingdom (UK)-PBC score.</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with LSM ≥15 kPa</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>Assessed by VCTE using Fibroscan®</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in serum levels of Aspartate aminotransferase (AST) compared to the baseline</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in serum levels of ALT compared to the baseline</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in serum levels of Gamma-glutamyl transferase (GGT) compared to the baseline</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in hepatic function: total and conjugated bilirubin</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in serum levels of Albumin compared to the baseline</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in hepatic function: international normalised ratio (INR)</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in hepatic function: fractionated ALP</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with no worsening of LSM</measure>
      <time_frame>At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>Assessed by VCTE using Fibroscan® defined as no increase &gt;2kPa from baseline</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with ALP reduction of 40%</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with ALP &lt;1.5x ULN, ALP decrease ≥15% and TB ≤ULN</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with ALP &lt;1.5x ULN, ALP decrease ≥40% and TB ≤ULN</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with ALP &lt;1.67x ULN, ALP decrease ≥15% and TB ≤ULN</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with ALP &lt;3x ULN, AST &lt;2x ULN and TB ≤1 mg/dL (Paris I)</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with ALP ≤1.5x ULN, AST ≤1.5x ULN and TB ≤1 mg/dL (Paris II criteria)</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with normalisation of abnormal TB</measure>
      <time_frame>Assessed at Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with normalisation of abnormal TB and albumin (Rotterdam criteria)</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with reduction in TB to ≤0.6x ULN in participants with TB &gt;0.6x ULN at baseline</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in lipid parameters: total cholesterol (TC)</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in lipid parameters: high density lipoprotein cholesterol (HDL-C)</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in lipid parameters: calculated very low density lipoprotein cholesterol (VLDL-C)</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in lipid parameters: low density lipoprotein cholesterol (LDL-C)</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in lipid parameters: triglycerides (TG)</measure>
      <time_frame>At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with a response in PBC Worst Itch NRS score</measure>
      <time_frame>Through 6 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>Defined as ≥2-point reduction from baseline NRS in participants with a baseline NRS ≥4</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Percentage of participants with a response in PBC Worst Itch NRS</measure>
      <time_frame>Assessed through 6 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>Defined as ≥3-point reduction from baseline NRS in participants with a baseline NRS ≥4</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in 5D-Itch scale</measure>
      <time_frame>Assessed at every 6 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in Patient Global Impression of Severity (PGI-S)</measure>
      <time_frame>Assessed at every 6 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>A 1-item, 5-point scale designed to assess the participant's impression of disease severity</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in Patient Global Impression of Change (PGI-C)</measure>
      <time_frame>Assessed at every 6 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>A 1-item, 5-point scale designed to assess the participant's impression of change in disease severity since the baseline visit</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form 7a</measure>
      <time_frame>Assessed at every 6 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in the Epworth Sleepiness Scale (ESS)</measure>
      <time_frame>Assessed at every 6 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in PBC-40 score</measure>
      <time_frame>Assessed at every 6 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in PBC Worst Itch Numeric Rating Scale (NRS) score</measure>
      <time_frame>Assessed through 6 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>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</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in EuroQol 5-dimensional 5-level questionnaire (EQ-5D-5L)</measure>
      <time_frame>Assessed at every 6 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in Work Productivity and Activity Impairment General Health (WPAI-GH)</measure>
      <time_frame>Assessed at every 6 months up to end of treatment (maximum duration of 7 years)</time_frame>
      <description>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).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to the first occurrence of each of individual adjudicated clinical outcome events</measure>
      <time_frame>From baseline until 4 weeks after the end of treatment</time_frame>
      <description>Among: • All-cause mortality • Liver-related mortality • Liver transplantation • Progression to cirrhosis • Progression to clinically significant portal hypertension • MELD-Na score ≥15 in participants with baseline MELD or MELD-Na score • Liver decompensation • Occurrence of hepatocellular carcinoma</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Area under the plasma concentration-time curve from time 0 to 24 hours: AUC0-24</measure>
      <time_frame>At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Maximum (peak) plasma drug concentration: Cmax</measure>
      <time_frame>At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Time to reach maximum (peak) plasma concentration following drug administration): Tmax</measure>
      <time_frame>At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Apparent clearance of drug from plasma (CL)</measure>
      <time_frame>At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Apparent volume of distribution (VZ)</measure>
      <time_frame>At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)</time_frame>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">450</enrollment>
    <condition>Primary Biliary Cholangitis (PBC)</condition>
    <arm_group>
      <arm_group_label>Elafibranor 80 mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>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.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>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.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Elafibranor</intervention_name>
      <description>Duration: up to an estimated 84-month (7-year) double-blind treatment period during which elafibranor 80 mg tablet will be administered once daily</description>
      <arm_group_label>Elafibranor 80 mg</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Matched 80 mg placebo</intervention_name>
      <description>Duration: up to an estimated 84-month (7-year) double-blind treatment period during which matching placebo tablet will be administered once daily</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria :&#xD;
  &#xD;
            -  Male or female participants must be ≥18 years of age at the time of signing the&#xD;
               informed consent.&#xD;
  &#xD;
            -  Participants with a definite or probable diagnosis of primary biliary cholangitis&#xD;
               (PBC)&#xD;
  &#xD;
            -  Participants taking ursodeoxycholic acid (UDCA) for at least 12 months (at a stable&#xD;
               dose for ≥3 months) prior to screening period and expected to remain on stable dose&#xD;
               during the study, or unable to tolerate UDCA treatment (no UDCA for ≥3 months) prior&#xD;
               to screening period (per country standard-of-care dosing).&#xD;
  &#xD;
            -  Participants taking medications for management of pruritus (e.g. cholestyramine,&#xD;
               rifampin, naltrexone, sertraline or colchicine) must be on a stable dose for ≥3 months&#xD;
               prior to screening period.&#xD;
  &#xD;
            -  Contraceptive use by men or women should be consistent with local regulations&#xD;
               regarding the methods of contraception for those participating in clinical studies.&#xD;
  &#xD;
            -  Capable of giving signed informed consent which includes compliance with the&#xD;
               requirements and restrictions listed in the informed consent form (ICF) and in this&#xD;
               protocol.&#xD;
  &#xD;
          Exclusion Criteria :&#xD;
  &#xD;
            -  History or presence of other concomitant liver disease including but not limited to:&#xD;
               i) Primary sclerosing cholangitis (PSC). ii) Autoimmune hepatitis (AIH) by simplified&#xD;
               Diagnostic Criteria of the International Autoimmune Hepatitis Group (IAIHG) ≥6, or if&#xD;
               treated for an overlap of PBC with AIH, or if there is clinical suspicion and evidence&#xD;
               of overlap AIH features, that cannot be explained alone by insufficient response to&#xD;
               UDCA. iii) Positive hepatitis B surface antigen (HBsAg). Participants with negative&#xD;
               HBsAg and positive hepatitis B core antibody (HBcAb) may be eligible if hepatitis B&#xD;
               virus deoxyribonucleic acid (HBV DNA) is negative. iv) Hepatitis C virus (HCV)&#xD;
               infection defined by positive anti-HCV antibody and positive HCV ribonucleic acid&#xD;
               (RNA) (Note: Participants with positive anti-HCV antibody due to previously treated&#xD;
               HCV infection, may be enrolled if a confirmatory HCV RNA is undetectable and sustained&#xD;
               viral response has been documented). v) Alcohol-associated liver disease (ALD). vi)&#xD;
               Nonalcoholic steatohepatitis (NASH). vii) Other chronic liver diseases, such as&#xD;
               alpha-1 antitrypsin deficiency.&#xD;
  &#xD;
            -  History or presence of clinically significant hepatic decompensation, including: i)&#xD;
               History of liver transplantation, current placement on a liver transplant list,&#xD;
               current model for end-stage liver disease (MELD)-Na score ≥12 due to hepatic&#xD;
               impairment (MELD-Na will be calculated only when MELD &gt;11). ii) Evidence of&#xD;
               complications of cirrhosis, including hepatic decompensation or evidence of&#xD;
               significant portal hypertension complications including presence of ascites requiring&#xD;
               treatment; history of variceal bleeding or related interventions (e.g. variceal&#xD;
               banding, or transjugular intrahepatic portosystemic shunt (TIPS) placement); presence&#xD;
               of hepatic encephalopathy Grade 2 or higher per West-Haven criteria; history or&#xD;
               presence of spontaneous bacterial peritonitis. Note: participants with low-risk&#xD;
               varices (Grade I) without history of bleeding or other treatment may be eligible to&#xD;
               enrol. iii) Hepatorenal syndrome (HRS) (type I or II).&#xD;
  &#xD;
            -  Known history of human immunodeficiency virus (HIV) infection or having a positive&#xD;
               confirmatory test for HIV type 1 or 2.&#xD;
  &#xD;
            -  Medical conditions that may cause non-hepatic increases in ALP (e.g. Paget's disease).&#xD;
  &#xD;
            -  Evidence of any other unstable or untreated clinically significant immunological,&#xD;
               endocrine, hematologic, gastrointestinal, neurological, or psychiatric disease as&#xD;
               evaluated by the investigator; other clinically significant conditions that are not&#xD;
               well controlled.&#xD;
  &#xD;
            -  Non-hepatic medical conditions that may diminish life expectancy to &lt;2 years,&#xD;
               including known cancers.&#xD;
  &#xD;
            -  History of hepatocellular carcinoma.&#xD;
  &#xD;
            -  Alpha-fetoprotein (AFP) &gt;20 ng/mL with 4-phase liver computerised tomography (CT) or&#xD;
               magnetic resonance imaging (MRI) imaging suggesting presence of hepatocellular&#xD;
               carcinoma.&#xD;
  &#xD;
            -  Known malignancy or history of malignancy within the last 5 years, with the exception&#xD;
               of local, successfully treated basal cell carcinoma or in-situ carcinoma of the&#xD;
               uterine cervix.&#xD;
  &#xD;
            -  Administration of the following medications is prohibited during the study, and prior&#xD;
               to the study as per the timelines specified below: i) 3 months prior to screening&#xD;
               period: fibrates, seladelpar, glitazones, obeticholic acid, azathioprine,&#xD;
               cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other&#xD;
               systemic corticosteroids (parenteral and oral chronic administration only);&#xD;
               potentially hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid,&#xD;
               isoniazid or nitrofurantoin).&#xD;
  &#xD;
            -  Participants with previous exposure to elafibranor.&#xD;
  &#xD;
            -  Participants who are currently participating in, plan to participate in, or have&#xD;
               participated in an investigational drug study or medical device study containing&#xD;
               active substance within 30 days or 5 half-lives, whichever is longer, prior to the&#xD;
               screening period.&#xD;
  &#xD;
               i) If the previous study was for an experimental therapy being studied for potential&#xD;
               benefit in PBC, and the potential therapeutic agent was proven to have no beneficial&#xD;
               effect in PBC and there are no safety concerns, the participant may enrol after 30&#xD;
               days or 5 half-lives from the last dose of the therapeutic agent, whichever is longer.&#xD;
               ii) For therapeutic agents being studied for potential benefit in PBC for which it is&#xD;
               still unclear if there may be a potential benefit, participants may enrol after 6&#xD;
               months from the last dose of the therapeutic agent.&#xD;
  &#xD;
            -  Electrocardiogram (ECG) with QT interval corrected by Fridericia's formula (QTcF) &gt;450&#xD;
               msec in males or QTcF &gt;470 msec in females for participants without bundle branch&#xD;
               block. For participants with bundle branch block or other intraventricular conduction&#xD;
               delay, a longer QTcF &gt;480 msec would be exclusionary.&#xD;
  &#xD;
            -  Total bilirubin (TB) &gt;2x ULN.&#xD;
  &#xD;
            -  Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) &gt;5x ULN at SV1,&#xD;
               or variability &gt;40% based on two consecutive values. The interval between the two&#xD;
               measurements should be of at least 2 weeks (and up to 4 weeks):&#xD;
  &#xD;
            -  Creatinine phosphokinase (CPK) &gt;2x ULN.&#xD;
  &#xD;
            -  Platelet count &lt;75,000/μL&#xD;
  &#xD;
            -  International normalised ratio (INR) &gt;1.5 in the absence of anticoagulant therapy.&#xD;
  &#xD;
            -  Estimated glomerular filtration rate (eGFR) &lt;45 mL/min/1.73m2 per the Modification of&#xD;
               Diet in Renal Disease (MDRD)-6 Study formula at SV1.&#xD;
  &#xD;
            -  Significant renal disease, including nephritic syndrome, chronic kidney disease&#xD;
               (defined as participants with evidence of significantly impaired kidney function or&#xD;
               underlying kidney injury).&#xD;
  &#xD;
            -  For female participants: known current pregnancy, or has a positive serum pregnancy&#xD;
               test, or is breastfeeding.&#xD;
  &#xD;
            -  Regular alcohol intake in excess of the recommended limit of 1 standard drink per day&#xD;
               for men or women.&#xD;
  &#xD;
            -  History of alcohol abuse, or other substance abuse within 1 year prior to SV1.&#xD;
  &#xD;
            -  A positive drug screen at screening would be exclusionary unless it can be explained&#xD;
               by a prescribed medication. Use of cannabidiol (CBD) or other cannabinoids is not&#xD;
               exclusionary for this study.&#xD;
  &#xD;
            -  Known hypersensitivity to elafibranor or to any of the excipients of the&#xD;
               investigational product(s).&#xD;
  &#xD;
            -  Mental instability or incompetence, such that the validity of informed consent or&#xD;
               ability to be compliant with the study is uncertain.&#xD;
  &#xD;
            -  Any other condition that, in the opinion of the investigator, would interfere with&#xD;
               study participation or completion, or would put the participant at risk, including a&#xD;
               potential participant assessed as being at high risk of noncompliance with the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Ipsen Medical Director</last_name>
      <role>Study Director</role>
      <affiliation>Ipsen</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ipsen Clinical Study Enquiries</last_name>
      <phone>See e mail</phone>
      <email>clinical.trials@ipsen.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Arizona Liver Health</name>
        <address>
          <city>Tucson</city>
          <state>Arizona</state>
          <zip>85641</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Active, not recruiting</status>
    </location>
    <location>
      <facility>
        <name>Peak Gastroenterology Associates</name>
        <address>
          <city>Colorado Springs</city>
          <state>Colorado</state>
          <zip>80829</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
    </location>
    <location>
      <facility>
        <name>Texas Clinical Research Institute</name>
        <address>
          <city>Arlington</city>
          <state>Texas</state>
          <zip>22201</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Active, not recruiting</status>
    </location>
    <location>
      <facility>
        <name>American Research Corporation at The Texas Liver Institute</name>
        <address>
          <city>San Antonio</city>
          <state>Texas</state>
          <zip>78015</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 22, 2023</study_first_submitted>
    <study_first_submitted_qc>August 29, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>September 12, 2023</last_update_submitted>
    <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cholangitis</mesh_term>
      <mesh_term>Liver Cirrhosis, Biliary</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>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.&#xD;
  Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.</ipd_description>
      <ipd_time_frame>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.</ipd_time_frame>
      <ipd_access_criteria>Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).</ipd_access_criteria>
      <ipd_url>https://vivli.org/members/ourmembers/</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06016842
  org study id: CLIN-60190-454
  secondary id: 2023-505251-43-00
  nct id: NCT06016842
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The participants of this study will have confirmed Primary Biliary Cholangitis (PBC).
  
        Participants will also have inadequate response or intolerance to ursodeoxycholic acid (UDCA)
        a drug used to treat PBC.
  
        PBC is a disease that progresses slowly. It causes 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 scarring (cirrhosis). PBC may also be associated with
        multiple symptoms. Many people 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). Each participant will be in the study up to about 7 years.
  
        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.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Triple (Participant, Investigator, Outcomes Assessor)
  measure: Event-free survival
  time frame: From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)
  description: Event-free survival is defined as the time from start of treatment to either adjucated disease progression or death, whichever occurs first.
  measure: Percentage of participants experiencing Treatment Emergent Adverse Events (TEAEs), treatment-related TEAEs, Serious Adverse Events (SAEs), and Adverse Events of Special Interests (AESIs)
  time frame: From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)
  description: 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.
  measure: Percentage of participants developing clinically significant changes in physical examination findings
  time frame: From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)
  description: Complete physical examination at screening and targeted examination at all other clinical visit timepoints.
  measure: Percentage of participants developing clinically significant changes in vital signs
  time frame: From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)
  description: Percentage of participants with clinically significant changes in Vital Signs will be reported. The clinical significance will be graded by the investigator.
  measure: Percentage of participants developing clinically significant changes in Electrocardiogram (ECG) readings.
  time frame: From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)
  description: Percentage of participants with clinically significant changes in ECG readings will be reported. The clinical significance will be graded by the investigator.
  measure: Percentage of participants with clinically significant changes in laboratory parameters (blood chemistry, hematology, coagulation and urinalysis)
  time frame: From baseline until 4 weeks after the end of treatment (maximum duration of 7 years)
  description: 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.
  measure: Change from baseline in Alkaline phosphatase (ALP)
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change from baseline in Total Bilirubin (TB)
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with ALP≤ 1.67x ULN and TB≤ ULN
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with complete biochemical response
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  description: Defined as normal levels of TB, ALP, transaminases, albumin, and International normalised ratio (INR)
  measure: Percentage of participants with normalisation of TB and ALP
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  description: Defined as TB< Upper Limit Normal (ULN) and ALP< ULN
  measure: Percentage of participants with stabilisation in TB (i.e. no increase)
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  description: Defined as TB< 1x ULN or increase from baseline <0.1x ULN
  measure: Percentage of participants with a response based on albumin normalisation
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change from baseline in liver stiffness measurement (LSM)
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  description: Assessed by vibration-controlled transient elastography (VCTE) using Fibroscan® on the day of the visit.
  measure: Change from baseline in PBC risk scores based in Global PBC Study Group (GLOBE) score
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  description: 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.
  measure: Change from baseline in PBC risk scores based on United Kingdom (UK)-PBC score.
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  description: 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.
  measure: Percentage of participants with LSM ≥15 kPa
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  description: Assessed by VCTE using Fibroscan®
  measure: Change in serum levels of Aspartate aminotransferase (AST) compared to the baseline
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change in serum levels of ALT compared to the baseline
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change in serum levels of Gamma-glutamyl transferase (GGT) compared to the baseline
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change from baseline in hepatic function: total and conjugated bilirubin
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change in serum levels of Albumin compared to the baseline
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change from baseline in hepatic function: international normalised ratio (INR)
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change from baseline in hepatic function: fractionated ALP
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with no worsening of LSM
  time frame: At Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  description: Assessed by VCTE using Fibroscan® defined as no increase >2kPa from baseline
  measure: Percentage of participants with ALP reduction of 40%
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with ALP <1.5x ULN, ALP decrease ≥15% and TB ≤ULN
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with ALP <1.5x ULN, ALP decrease ≥40% and TB ≤ULN
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with ALP <1.67x ULN, ALP decrease ≥15% and TB ≤ULN
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with ALP <3x ULN, AST <2x ULN and TB ≤1 mg/dL (Paris I)
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with ALP ≤1.5x ULN, AST ≤1.5x ULN and TB ≤1 mg/dL (Paris II criteria)
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with normalisation of abnormal TB
  time frame: Assessed at Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with normalisation of abnormal TB and albumin (Rotterdam criteria)
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with reduction in TB to ≤0.6x ULN in participants with TB >0.6x ULN at baseline
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change from baseline in lipid parameters: total cholesterol (TC)
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change from baseline in lipid parameters: high density lipoprotein cholesterol (HDL-C)
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change from baseline in lipid parameters: calculated very low density lipoprotein cholesterol (VLDL-C)
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change from baseline in lipid parameters: low density lipoprotein cholesterol (LDL-C)
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Change from baseline in lipid parameters: triglycerides (TG)
  time frame: At Month 6, Month 12, and every 12 months up to end of treatment (maximum duration of 7 years)
  measure: Percentage of participants with a response in PBC Worst Itch NRS score
  time frame: Through 6 months up to end of treatment (maximum duration of 7 years)
  description: Defined as ≥2-point reduction from baseline NRS in participants with a baseline NRS ≥4
  measure: Percentage of participants with a response in PBC Worst Itch NRS
  time frame: Assessed through 6 months up to end of treatment (maximum duration of 7 years)
  description: Defined as ≥3-point reduction from baseline NRS in participants with a baseline NRS ≥4
  measure: Change from baseline in 5D-Itch scale
  time frame: Assessed at every 6 months up to end of treatment (maximum duration of 7 years)
  description: 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.
  measure: Change from baseline in Patient Global Impression of Severity (PGI-S)
  time frame: Assessed at every 6 months up to end of treatment (maximum duration of 7 years)
  description: A 1-item, 5-point scale designed to assess the participant's impression of disease severity
  measure: Change from baseline in Patient Global Impression of Change (PGI-C)
  time frame: Assessed at every 6 months up to end of treatment (maximum duration of 7 years)
  description: A 1-item, 5-point scale designed to assess the participant's impression of change in disease severity since the baseline visit
  measure: Change from baseline in Patient Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form 7a
  time frame: Assessed at every 6 months up to end of treatment (maximum duration of 7 years)
  description: 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.
  measure: Change from baseline in the Epworth Sleepiness Scale (ESS)
  time frame: Assessed at every 6 months up to end of treatment (maximum duration of 7 years)
  description: 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).
  measure: Change from baseline in PBC-40 score
  time frame: Assessed at every 6 months up to end of treatment (maximum duration of 7 years)
  description: 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.
  measure: Change from baseline in PBC Worst Itch Numeric Rating Scale (NRS) score
  time frame: Assessed through 6 months up to end of treatment (maximum duration of 7 years)
  description: 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
  measure: Change from baseline in EuroQol 5-dimensional 5-level questionnaire (EQ-5D-5L)
  time frame: Assessed at every 6 months up to end of treatment (maximum duration of 7 years)
  description: 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).
  measure: Change from baseline in Work Productivity and Activity Impairment General Health (WPAI-GH)
  time frame: Assessed at every 6 months up to end of treatment (maximum duration of 7 years)
  description: 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).
  measure: Time to the first occurrence of each of individual adjudicated clinical outcome events
  time frame: From baseline until 4 weeks after the end of treatment
  description: Among: • All-cause mortality • Liver-related mortality • Liver transplantation • Progression to cirrhosis • Progression to clinically significant portal hypertension • MELD-Na score ≥15 in participants with baseline MELD or MELD-Na score • Liver decompensation • Occurrence of hepatocellular carcinoma
  measure: Area under the plasma concentration-time curve from time 0 to 24 hours: AUC0-24
  time frame: At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
  measure: Maximum (peak) plasma drug concentration: Cmax
  time frame: At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
  measure: Time to reach maximum (peak) plasma concentration following drug administration): Tmax
  time frame: At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
  measure: Apparent clearance of drug from plasma (CL)
  time frame: At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
  measure: Apparent volume of distribution (VZ)
  time frame: At Day 1/Baseline, Month 6 and Month 12 (during a dosing period of 24 hours)
  arm group label: Elafibranor 80 mg
  arm group type: Experimental
  description: 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.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: 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.
  intervention type: Drug
  intervention name: Elafibranor
  description: Duration: up to an estimated 84-month (7-year) double-blind treatment period during which elafibranor 80 mg tablet will be administered once daily
  arm group label: Elafibranor 80 mg
  intervention type: Other
  intervention name: Matched 80 mg placebo
  description: Duration: up to an estimated 84-month (7-year) double-blind treatment period during which matching placebo tablet will be administered once daily
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Ipsen Medical Director
  role: Study Director
  affiliation: Ipsen
  last name: Ipsen Clinical Study Enquiries
  phone: See e mail
  email: clinical.trials@ipsen.com
  facility: 
  status: Active, not recruiting
  facility: 
  status: Recruiting
  facility: 
  status: Active, not recruiting
  facility: 
  status: Not yet recruiting
  country: United States
  responsible party type: Sponsor
  mesh term: Cholangitis
  mesh term: Liver Cirrhosis, Biliary
  sharing ipd: Yes
  ipd description: 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.
  ipd time frame: 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.
  ipd access criteria: Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
  ipd url: https://vivli.org/members/ourmembers/