Primary Biliary CholangitisPhase 3ELONSENNCT06730061
A Study of Elafibranor in Adult Japanese Participants With Primary Biliary Cholangitis (PBC)
A Phase 3 study testing Elafibranor in people with Primary Biliary Cholangitis, run by Ipsen at 16 sites in Japan.
Trial summary
The purpose of this study is to find out about the safety and how well the study intervention (elafibranor) works in participants with PBC. The participants in this study will have confirmed PBC with inadequate response or intolerance to UDCA, which is a medication used in the management and treatment of cholestatic… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Primary Biliary Cholangitis
- What is being tested?
- Elafibranor
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 16 sitesJapan
- Study dates
- 16 Jan 2025to 8 Apr 2032
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have provided written informed consent and agree to comply with the study protocol.
- Japanese male or female participants aged 18 to 75 years inclusive at Screening Visit 1 (SV1).
- PBC diagnosis as described in the study protocol
- ALP ≥1.67×ULN (mean value based on samples collected at SV1 and SV2).
- TB ≤2×ULN at SV1 and SV2.
- Must have at least 4 available values for PBC Worst Itch Numeric Rating Scale (NRS) during each of the 7-day intervals in the 14 days prior to visit (V)1, for a total of at least 8 values for PBC Worst Itch NRS in the last 14 days prior to V1.
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- Participants taking UDCA for at least 12 months (stable dose ≥3 months) prior to screening, or unable to tolerate UDCA treatment (no UDCA for ≥3 months) prior to screening (per country standard-of-care dosing).
- If on colchicine, must be on a stable dose for ≥3 months prior to screening.
- Medications for management of pruritus (for example, cholestyramine, rifampicin, naltrexone, sertraline or nalfurafine hydrochloride) must be on a stable dose for ≥3 months prior to screening.
- Participants taking statins or ezetimibe must be on a stable dose for ≥2 months prior to screening.
- Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
Who cannot join
- History or presence of other concomitant liver disease
- Participants with known cirrhosis who have a Child-Pugh B or C classification.
- Participants with cirrhosis with Child-Pugh A classification are allowed.
- History or presence of clinically significant hepatic decompensation,
- Medical conditions that may cause non-hepatic increases in ALP (for example, Paget's disease) or which may diminish life expectancy to <2 years, including known cancers.
- 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.
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- Participant has a positive test for human immunodeficiency virus (HIV) Type 1 or 2 at screening, or participant is known to have tested positive for HIV.
- Evidence of any other unstable or untreated clinically significant immunological, endocrine, haematologic, gastrointestinal, neurological, or psychiatric disease as evaluated by the investigator; other clinically significant medical conditions that are not well controlled.
- History of alcohol abuse, defined as consumption of more than 30 g pure alcohol per day for men, and more than 20 g pure alcohol per day for women, or other substance abuse within 1 year prior to SV1.
- For female participants: known pregnancy, or has a positive serum pregnancy test, or breastfeeding.
- Administration of the following medications are prohibited as specified below:
- 1 month prior to screening: fibrates.
- 2 months prior to screening: glitazones.
- For participants with previous exposure to obeticholic acid (OCA), OCA should be discontinued 3 months prior to screening.
- 3 months prior to screening: azathioprine, cyclosporine (systemic), methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (parenteral and oral chronic administration only); potentially hepatotoxic drugs (including α-methyldopa, sodium valproate/valproic acid isoniazid, or nitrofurantoin).
- 12 months prior to screening: antibodies or immunotherapy directed against interleukins (ILs) or other cytokines or chemokines.
- 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 screening; for participants with previous exposure to seladelpar, seladelpar should be discontinued 3 months prior to screening.
- Participants with previous exposure to elafibranor.
- SV1 or SV2 value ALT and/or AST >5×ULN.
- For participants with aminotransferases or TB >ULN at SV1, variability (between SV1 and SV2) of aminotransferases or TB >40%.
- SV1 value albumin <3.0 g/dL.
- Severely advanced participants according to Rotterdam criteria (TB >ULN and albumin <LLN).
- SV1 international normalised ratio (INR) >1.3 due to altered hepatic function.
- SV1 creatine phosphokinase (CPK) >2×ULN.
- SV1 serum creatinine >1.5 mg/dL.
- Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as participants with markers of kidney failure damage or estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2) calculated by modification of diet in renal disease study (MDRD).
- SV1 platelet count <150×103/μL.
- Alpha-fetoprotein (AFP) >20 ng/mL with 4-phase liver computerised tomography (CT) or magnetic resonance imaging (MRI) imaging suggesting presence of liver cancer.
- Known hypersensitivity to the investigational product or to any of the formulation excipients of the elafibranor tablet.
- Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Japan16 sites
Nippon Medical School - Chiba Hokusoh Hospital
Chiba
Fukushima Medical University Hospital
Fukushima
Chugoku Rosai Hospital
Hiroshima
Teine Keijinkai Hospital
Hokkaido
Kagawa University Hospital
Kagawa
Kagoshima University Hospital
Kagoshima
Shinshu University Hospital
Nagano
National Hospital Organization Nagasaki Medical Center
Nagasaki
Nara Medical University Hospital
Nara
Nagaoka Red Cross Hospital
Niigata
Niigata University Medical & Dental Hospital
Niigata
National Hospital Organization Osaka National Hospital
Osaka
Hamamatsu University Hospital
Shizuoka
Juntendo University Hospital
Tokyo
Teikyo University Hospital
Tokyo
Tokyo Metropolitan Komagome Hospital
Tokyo
About this study
Official title: A Phase III, Open-label, Single Arm Study to Investigate the Efficacy and Safety of Elafibranor 80 mg in Adult Japanese Participants With Primary Biliary Cholangitis (PBC)
The purpose of this study is to find out about the safety and how well the study intervention (elafibranor) works in participants with PBC. The participants in this study will have confirmed PBC with inadequate response or intolerance to UDCA, which is a medication used in the management and treatment of cholestatic liver disease.
PBC 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).
Read more
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. In this study all participants will receive a daily dose of elafibranor (the study intervention).
The main aim of this study is to determine if elafibranor reduces alkaline phosphatase (ALP) and total bilirubin levels. High ALP and bilirubin levels in the blood can indicate liver disease.
There will be 4 periods in this study: A screening period (up to 10 weeks) to assess whether the participant can take part. A treatment period (52 weeks) where all eligible participants will receive elafibranor. A variable treatment extension period (2-5 years) from End Of Treatment (EOT) period up to the commercial availability of elafibranor in Japan. A follow-up period (4 weeks) where participants' health will be monitored.
Participants will undergo blood sampling, urine collections, physical examinations, clinical evaluations, electrocardiograms (ECG: recording of the electrical activity of heart), ultrasound examinations (a non-invasive test that passes a probe over skin to look at the bladder, urinary tract, and liver), and Fibroscan® examinations (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 approximately 6 years
- Conditions
- Primary Biliary Cholangitis
- Being tested
- Elafibranor
- Medical subject headings
- Liver Cirrhosis, Biliary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElafibranorDrug
Tablet of 80 mg
| Study group | Role | What they receive |
|---|---|---|
| Elafibranor | Experimental | Participants will take the study intervention by mouth (swallow whole) once daily Receives: Drug: Elafibranor |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of participants with Alkaline phosphatase (ALP) <1.67x ULN, ALP decrease ≥15% and Total Bilirubin (TB) ≤ ULN
Measured: At Week 52
Secondary outcomes (43)
Percentage of Participants who normalised ALP Levels
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in ALP Levels
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of Participants With ALP Level response
Defined as 10%, 20% and 40% ALP reduction from baseline
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with ALP <1.5×ULN, ALP decrease ≥40% and TB ≤ULN.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with ALP <3×ULN, aspartate aminotransferase (AST) <2×ULN and Total Bilirubin (TB) <1 mg/dL (Paris I criteria).
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with ALP ≤1.5×ULN, AST ≤1.5×ULN and TB ≤ULN (Paris II criteria).
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with TB response rate of 15% change.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with normalisation of abnormal TB and/or albumin (Rotterdam criteria).
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with TB ≤0.6×ULN
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with ALP ≤1.67×ULN and TB ≤1 mg/dL.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with no worsening of TB Levels
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with complete biochemical response
Defined as normal ALP; TB; AST; alanine aminotransferase (ALT); albumin; and INR.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with ALP ≤1.67×ULN, ALP decrease ≥15% and TB ≤ULN.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with ALP <1.5×ULN, ALP decrease ≥15% and TB ≤ULN.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants with ALP ≤ULN and TB ≤ULN.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in PBC risk scores based in Global PBC Study Group (GLOBE) score
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.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in PBC risk scores based on United Kingdom (UK)-PBC score.
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.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Response based on the normalisation of bilirubin.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Response based on the normalisation of albumin Levels.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in hepatobiliary injury and liver function
Hepatobiliary injury and liver function will be measured by AST, ALT, gamma-glutamyl transferase (GGT), 5'nucleotidase (5' NT), total and conjugated bilirubin, albumin, INR, and ALP fractionated (hepatic).
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in lipid parameters
Lipid parameters as measured by total cholesterol (TC), low-density lipoprotein cholesterol ( LDL-C), high-density lipoprotein cholesterol (HDL-C), calculated very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TG).
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in liver stiffness measurement (LSM)
Assessed by vibration-controlled transient elastography (VCTE) using Fibroscan®
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in pruritus
Based on PBC Worst Itch Numeric Rating Scale (NRS) score in participants with baseline PBC Worst Itch NRS score ≥4.
Measured: At Week 26, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Proportion of responders in PBC Worst Itch NRS according to clinically meaningful change from baseline
At least 30% reduction; and one point, two points or three points decrease in score in participants with a baseline NRS score ≥4.
Measured: At Week 26 and at Week 52 and every 26 weeks until the end of study (up to 6 years)
Proportion of participants with no worsening of pruritus from baseline
Measured: At Week 26 and at Week 52 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in 5D-Itch scale
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.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a scores
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.
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in Epworth Sleepiness Scale (ESS).
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).
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in PBC-40.
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).
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in EuroQol 5-dimensional 5-level questionnaire (EQ-5D-5L)
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).
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in Patient Global Impression of Severity (PGI-S)
A 1-item, 5-point scale designed to assess the participant's impression of change in disease severity since the baseline visit
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Patient Global Impression of Change (PGI-C)
A 1-item, 5-point scale designed to assess the participant's impression of change in disease severity since the baseline visit
Measured: At Week 4, Week 13, Week 26, Week 39, and Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)]
Time to the first occurrence of each of individual adjudicated clinical outcome events
Measured: At Week 4, Week 13, Week 26, Week 39, Week 52, Week 78 and every 26 weeks until the end of study (up to 6 years)
Percentage of participants who experience Treatment Emergent Adverse Events (TEAEs), treatment related TEAEs, Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs).
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.
Measured: From baseline to end of study (up to 6 years)
Percentage of participants who develop clinically significant changes from baseline in physical examination findings
Clinically significant change in physical examination findings will be reported. The clinical significance will be graded by the investigator.
Measured: From baseline to end of study (up to 6 years)
Percentage of participants who develop clinically significant changes from baseline in vital signs
Clinically significant change in vital signs will be reported. The clinical significance will be graded by the investigator.
Measured: From baseline to end of study (up to 6 years)
Percentage of participants with clinically significant changes in laboratory parameters (blood chemistry, hematology, liver tests, renal tests (including urinalysis).
Clinically significant change in laboratory parameters will be reported. The clinical significance will be graded by the investigator.
Measured: From baseline to end of study (up to 6 years)
Percentage of participants who develop clinically significant changes from baseline in ECG readings
Clinically significant change in ECG readings. The clinical significance will be graded by the investigator.
Measured: From baseline to end of study (up to 6 years)
Change from baseline in fasting plasma glucose (FPG) Levels
Measured: At Week 52 and every 26 weeks until the end of study (up to 6 years)
Change from baseline in serum markers of bone turnover and in bone mineral density (hip and lumbar)
Assessed by dual-energy X-ray absorptiometry (DEXA) scanning.
Measured: At Week 52 and every 26 weeks until the end of study (up to 6 years)
Area under the plasma concentration-time curve from time 0 to 24 hours: AUC0-24
Measured: At Week 4
Maximum (peak) plasma drug concentration: Cmax
Measured: At Week 4
Time to reach maximum (peak) plasma concentration following drug administration): Tmax
Measured: At Week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2024
- Study start16 Jan 2025
- Primary completion17 Dec 2026 (estimated)
- Study completion8 Apr 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Biliary CholangitisStudies of the same condition, open and under way.
- More trials run by IpsenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ipsen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ipsen Medical, Director, Study director, Ipsen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06730061
- Sponsor's protocol ID
- CLIN-60190-462
- Acronym
- ELONSEN
- Status last verified
- Oct 2026
- First submitted
- 3 Dec 2024
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.