A Study of Elafibranor in Adults With Primary Biliary Cholangitis and Inadequate Response or Intolerance to Ursodeoxycholic Acid.
- Conditions
- Primary Biliary Cholangitis
- Interventions
- Other: Placebo
- Registration Number
- NCT06383403
- Lead Sponsor
- Ipsen
- Brief Summary
The participants in this study will have confirmed PBC with inadequate response or intolerance to Ursodeoxycholic acid (UDCA), which is a medication used in the management and treatment of cholestatic liver disease.
Primary biliary cholangitis is a slowly progressive disease characterised by damage of 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 patients with PBC may require a 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).
The main aim of this study is to determine if elafibranor is better than placebo in reducing ALP levels to a normal value. High ALP levels in the blood can indicate liver disease.
There will be three periods in this study: A screening period (up to 8 weeks) to assess whether the participant can take part; a treatment period (up to 52 weeks) where eligible participants will be grouped as per their blood ALP levels and randomly assigned to either receive elafibranor or placebo, and a follow-up period (4 weeks) where participants' health will be monitored.
Participants will be twice as likely to receive elafibranor than placebo (2:1 ratio).
Participants will undergo blood sampling, urine collections, physical examinations, clinical evaluations, electrocardiograms (ECG: recording of the electrical activity of heart), ultrasound examinations (a noninvasive test that passes a probe over skin to look at the bladder, urinary tract, and liver), and Fibroscan® examinations (a noninvasive test that passes a probe on skin to measure stiffness of the liver).
They will also be asked to fill in questionnaires. Each participant will be in this study for up to 64 weeks (15 months).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 69
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants will take 1 placebo tablet per day orally before breakfast with a glass of water at approximately the same time each morning. Elafibranor 80 mg Elafibranor Participants will take 1 tablet of elafibranor 80 mg per day orally before breakfast with a glass of water at approximately the same time each morning.
- Primary Outcome Measures
Name Time Method Percentage of participants with normalisation of Alkaline Phosphate (ALP) Levels At Week 52
- Secondary Outcome Measures
Name Time Method Change from baseline in ALP levels From baseline to Week 4, Week 12, Week 24, Week 36 and Week 52 Change from baseline in PBC Worst Itch Numeric Rating Scale (NRS) score From baseline through Week 52 PBC Worst Itch Numeric Rating Scale (NRS) is a 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)
Percentage of participants with moderate to severe pruritus at baseline (i.e. score ≥4) with a clinically meaningful response in PBC Worst Itch NRS From baseline through Week 52 Defined as ≥1.8-point reduction from baseline
Percentage of participants developing clinically significant changes in Electrocardiogram (ECG) Readings From baseline until 4 weeks after the end of treatment (maximum duration of 52 weeks) The clinical significance will be graded by the investigator.
Percentage of participants with normalisation of ALP and TB <0.7 × ULN At Week 4, Week 12, Week 24, Week 36 and Week 52 Percentage of participants with normalisation of TB and ALP Levels At Week 4, Week 12, Week 24, Week 36 and Week 52 Change from baseline in 5-D itch score From baseline to Week 4, Week 24, and Week 52 Change from baseline in symptoms in terms of 5 domains: degree, duration, direction, disability and distribution. Patients rate their symptoms over the preceding 2-week period on a 1 to 5 scale, with 5 being the most affected.
Change from baseline in Patient Global Impression of Severity (PGI-S) scores From baseline to Week 4, Week 24, and Week 52 Patient Global Impression of Severity (PGI-S) is a 1-item, 5-point scale designed to assess the participant's impression of itch severity over the past 7 days, at different time points during the study.
Percentage of participants developing clinically significant changes in laboratory parameters From baseline until 4 weeks after the end of treatment (maximum duration of 52 weeks) The following laboratory parameters will be reported: blood chemistry, hematology and coagulation, liver tests and renal tests (including urinalysis). The clinical significance will be graded by the investigator.
Percentage of participants with normalisation of ALP Levels From baseline to Week 4, Week 12, Week 24 and Week 36 Percentage of participants with normalisation of ALP Levels and ≥15% decrease from Baseline From baseline to Week 4, Week 12, Week 24, Week 36 and Week 52 Percentage of participants with ≥40% decrease from Baseline in ALP Levels From baseline to Week 4, Week 12, Week 24, Week 36 and Week 52 Changes from baseline in Total Bilirubin (TB) Levels From baseline to Week 4, Week 12, Week 24, Week 36 and Week 52 Percentage of participants with ALP <0.5 × Upper Limit of Normal (ULN) At Week 4, Week 12, Week 24, Week 36 and Week 52 Percentage of participants with TB <0.7 × ULN At Week 4, Week 12, Week 24, Week 36 and Week 52 Percentage of participants with complete biochemical response At Week 4, Week 12, Week 24, Week 36 and Week 52 Defined as normal levels of TB, ALP, aminotransferases, albumin, and International normalised ratio (INR)
Change from baseline in PBC-40 Quality of Life (QoL) scores From baseline to Week 4, Week 24, and Week 52 PBC-40 Quality of Life (QoL) assesses symptoms across six domains: fatigue, emotional, social, cognitive function, general symptoms and itch. Patients 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'. Five items (3/3 in the itch domain and 2/10 in the social 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 1-5 per item (0-5 on items with a 'does not apply' option) with 5 being the most affected. The PBC-40 has a 4-week recall period.
Percentage of participants experiencing Treatment- Emergent Adverse Events (TEAEs), treatment- related TEAEs, Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs). From baseline until 4 weeks after the end of treatment (maximum duration of 52 weeks) An Adverse Event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered 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.
Patient Global Impression of Change (PGI-C) scores At Week 4, Week 24, and Week 52 Patient Global Impression of Change (PGI-C) is a 1-item, 5-point scale designed to assess the participant's impression of change in itch severity since the baseline visit
Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a scores From baseline to Week 4, Week 24, and Week 52 PROMIS Fatigue Short Form 7a scores 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.
Percentage of participants developing clinically significant changes in physical examination From baseline until 4 weeks after the end of treatment (maximum duration of 52 weeks) The clinical significance will be graded by the investigator.
Percentage of participants developing clinically significant changes in vital signs From baseline until 4 weeks after the end of treatment (maximum duration of 52 weeks) The clinical significance will be graded by the investigator.
Trial Locations
- Locations (60)
Institute for Clinical and Experimental Medicine - IKEM
🇨🇿Prague, Czechia
Research Site s.r.o.
🇨🇿Plzen, Czechia
Universitaetsklinikum Muenster
🇩🇪Münster, Germany
Ospedale Policlinico San Martino - IRCCS
🇮🇹Genova, Italy
Hepato-Gastroenterologie HK, s.r.o.
🇨🇿Hradec Králové, Czechia
Southern California Research Center
🇺🇸Coronado, California, United States
Topgraphy Health, Inc.
🇺🇸Los Angeles, California, United States
University of California, Davis
🇺🇸Sacramento, California, United States
Stanford University Medical Center
🇺🇸Stanford, California, United States
Peak Gastroenterology Associates
🇺🇸Colorado Springs, Colorado, United States
Rocky Mountain Gastroenterology
🇺🇸Littleton, Colorado, United States
International Center for Research
🇺🇸Tampa, Florida, United States
Delta Research Partners, LLC
🇺🇸West Monroe, Louisiana, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Huron Gastroenterology Associates - Center for Digestive Care
🇺🇸Ypsilanti, Michigan, United States
South Denver Gastroenterology,P.C.
🇺🇸Englewood, New Jersey, United States
Southwest Gastroenterology Associates, PC (SWGA)
🇺🇸Albuquerque, New Mexico, United States
Northwell Health Center for Liver Disease and Transplantation
🇺🇸Manhasset, New York, United States
Charlotte Gastroenterology & Hepatology, PLLC
🇺🇸Charlotte, North Carolina, United States
Coastal Research Institute
🇺🇸Fayetteville, North Carolina, United States
Gastroenterology Center of the Midsouth
🇺🇸Cordova, Tennessee, United States
Methodist Transplant Physicians
🇺🇸Dallas, Texas, United States
American Research Corporation at The Texas Liver Institute
🇺🇸San Antonio, Texas, United States
American Research Corporation
🇺🇸San Antonio, Texas, United States
Velocity Liver Institute NW
🇺🇸Seattle, Washington, United States
Artroscan
🇨🇿Ostrava, Czechia
Clinique Pasteur
🇫🇷Toulouse, France
Universitatsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Gastroenterologsiche Studiengesellschaft Herne
🇩🇪Hemer, Germany
EUGASTRO GmbH
🇩🇪Leipzig, Germany
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
🇮🇹Palermo, Italy
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
IRCCS Istituto clinico humanitas - Humanitas Mirasole spa
🇮🇹Rozzano, Italy
Korea University Ansan Hospital
🇰🇷Ansan si, Korea, Republic of
Keimyung University Dongsan Hospital
🇰🇷Daegu, Korea, Republic of
Kyungpook National University Hospital (KNUH)
🇰🇷Daegu, Korea, Republic of
Pusan National University Hospital (PNUH)
🇰🇷Pusan, Korea, Republic of
CHA Bundang Medical Center, CHA University
🇰🇷Seongnam-si, Korea, Republic of
Seoul National University Bundang Hospital (SNUBH)
🇰🇷Seongnam-si, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
The Catholic University of Korea, Eunpyeong St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Krakowskie Centrum Medyczne Sp.z.o.o - FutureMeds
🇵🇱Kraków, Poland
FutureMeds Warszawa Centrum
🇵🇱Warsaw, Poland
Cluj County Clinical Emergency Hospital
🇷🇴Cluj-Napoca, Romania
Gastromedica Srl
🇷🇴Iaşi, Romania
Hospital Clinic i Provincial de Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Universitario Puerta de Hierro de Majadahonda
🇪🇸Majadahonda, Spain
Institut d Investigacio i Innovacio Parc Tauli, Hospital Universitari Parc Tauli
🇪🇸Sabadell, Spain
Hospital Universitario Miguel Servet
🇪🇸Zaragoza, Spain
Aberdeen Royal Infirmary NHS Grampian Grampian Health Board
🇬🇧Aberdeen, United Kingdom
Bradford Royal Infirmary - Bradford Teaching Hospitals NHS Foundation
🇬🇧Bradford, United Kingdom
Frimley Park Hospital - Frimley Health NHS Foundation Trust
🇬🇧Frimley, United Kingdom
Queen Elizabeth University Hospital - Greater Glasgow Health Board
🇬🇧Glasgow, United Kingdom
Hull Royal Infirmary - Hull University Teaching Hospitals NHS Trust
🇬🇧Hull, United Kingdom
Ambrose King Centre-Royal London Hospital-Barts Health NHS Trust
🇬🇧London, United Kingdom
King's College Hospital
🇬🇧London, United Kingdom