Study of Elafibranor in Patients With Primary Biliary Cholangitis (PBC)

Phase 3

Active, not recruiting

• Conditions: Primary Biliary Cirrhosis
• Interventions: Drug: Elafibranor 80mg; Drug: Placebo

• Registration Number: NCT04526665
• Lead Sponsor: Ipsen

Brief Summary

The participants of this study will have confirmed Primary Biliary Cholangitis (PBC) with inadequate response or intolerance to ursodeoxycholic acid (which is a medication used in the management and treatment of cholestatic liver disease).

PBC is a slowly progressive disease characterized by damage of the bile ducts in the liver, leading to a buildup 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 liver transplant or may die if the disease progresses and a liver transplant is not done.

This study has two main parts; the first part will compare a daily dose of elafibranor (the study drug) to a daily dose of placebo (a dummy treatment), and will last between a minimum of one year and a maximum of two years. In the second part, all participants will receive elafibranor, for a period between 4-5 years.

The main aim of this study is to determine if elafibranor is better than placebo at decreasing the levels of a specific blood test (alkaline phosphatase) that provides information about participant's disease. This study will also study the safety of long-term treatment with elafibranor, as well as the impact on symptoms such as pruritus and fatigue.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-08-21
• Study First Submitted QC: 2020-08-21
• Study First Posted: 2020-08-26
• Study Start: 2020-09-24
• Primary Completion: 2023-06-01
• Disposition First Submitted: 2024-05-09
• Results First Submitted: 2024-07-10
• Results First Submitted QC: 2024-08-28
• Results First Posted: 2024-09-05
• Disposition First Posted: 2024-09-05
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-20
• Last Update Posted: 2024-12-27
• Study Completion: 2028-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 161

Inclusion Criteria

Not provided

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Exclusion Criteria

• History or presence of other concomitant liver disease
• Clinically significant hepatic decompensation, including patients with complications of cirrhosis/portal hypertension
• Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease) or which may diminish life expectancy to < 2 years, including known cancers
• Patient has a positive test for HIV Type 1 or 2 at screening, or patient is known to have tested positive for HIV
• Evidence of any other unstable or untreated clinically significant disease
• History of alcohol abuse
• For female patients: known pregnancy or lactating
• Use of fibrates and glitazones within 2 months prior to screening
• Use of OCA, azathioprine, cyclosporine, methotrexate, mycophenolate, pentoxifylline, budesonide and other systemic corticosteroids (parenteral and oral chronic administration only); potentially hepatotoxic drugs
• (including α-methyl-dopa, sodium valproic acid isoniazid, or nitrofurantoin) within 3 months prior to screening
• Use of antibodies or immunotherapy directed against interleukins (ILs) or other cytokines or chemokines within 12 months prior to screening
• For patients with previous exposure to obeticholic acid (OCA), OCA should be discontinued 3 months prior to screening
• Patients 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 five half-lives, whichever is longer, prior to screening; for patients with previous exposure to seladelpar, seladelpar should be discontinued 3 months prior to screening
• ALT and/or AST values > 5 x ULN
• For patients with AT or TB>ULN at SV1, variability of AT or TB > 40% (see section 3.5.1)
• Albumin<3.0 g/dl
• Severely advanced patients according to Rotterdam criteria (TB > ULN and albumin <LLN)
• INR > 1.3 due to altered hepatic function
• CPK > 2 x ULN
• Screening serum creatinine > 1.5 mg/dl
• Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as patients with markers of kidney failure damage or eGFR < 60 mL/min/1,73 m2) calculated by MDRD
• Platelet count < 150 x 103/μL
• AFP > 20 ng/mL with 4-phase liver CT or MRI imaging suggesting presence of liver cancer
• Known hypersensitivity to the investigational product or to any of the formulation excipients of the elafibranor or placebo tablet Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Elafibranor 80mg double-blind	Elafibranor 80mg	Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning
Placebo	Placebo	Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning
Elafibranor 80mg open label	Elafibranor 80mg	Study participants will take 1 tablet per day orally before breakfast with a glass of water each morning

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Response to Treatment Based on Cholestasis Response at Week 52	At Week 52	Cholestasis response was defined as alkaline phosphatase (ALP) \< 1.67 x upper limit of normal (ULN) and total bilirubin (TB) \<= ULN and ALP decrease from baseline \>= 15% at Week 52 and based on the composite strategy imputing non-response for participants who experienced intercurrent events (ICEs) (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in ALP at Weeks 4, 13, 26, 39 and 52	Baseline (Day 1) and at Weeks 4, 13, 26, 39 and 52	Blood samples were collected at specified timepoints for assessment of ALP. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Percentage of Participants With ALP Response From Baseline at Week 52	Baseline (Day 1) and at Week 52	ALP response was defined as ALP decrease from baseline \>= 10%; ALP decrease from baseline \>= 20% and ALP decrease from baseline \>= 40% at Week 52 and based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Percentage of Participants With Response to Treatment According to ALP < 1.5x ULN, ALP Decrease From Baseline >= 40% and TB =<ULN at Week 52	At Week 52	Response to treatment was according to ALP \< 1.5x ULN, ALP decrease from baseline \>= 40% and TB =\<ULN at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Global PBC Study Group (GLOBE) Score at Week 52	At Week 52	The GLOBE score was a validated risk assessment tool providing an estimate of transplant-free survival for participants with PBC. It was developed by the Global PBC Study Group using Cox regression model on over 4,000 participants with PBC. It is calculated from the following equation at week 52 as follows: GLOBE score = 0.044378 \* age at start of ursodeoxycholic acid (UDCA) therapy + 0.93982 \* LN (TB x ULN) + 0.335648 \* LN (ALP x ULN) - 2.266708 \* ALB x LLN - 0.002581 \* platelet count per 10\^9/L) + 1.216865; where TB x ULN = bilirubin/ULN at the timepoint, ALP x ULN = ALP/ULN at the timepoint, ALB x LLN = ALB/LLN at the timepoint, platelet count per 10\^9/L = platelet count per 10\^9/L at the timepoint. The Lower GLOBE PBC score predicts lower risk and better prognosis.
Change From Baseline in Hepatobiliary Injury and Liver Function as Assessed by AST, ALT, Gamma-glutamyl Transferase (GGT), 5 Prime Nucleotidase (5'-NT), and Fractionated ALP (Hepatic) (H1 and H2) at Week 52	Baseline (Day 1) and at Week 52	Hepatobiliary injury and liver function were assessed as measured by AST, ALT, GGT, 5'-NT, and fractionated ALP (hepatic) (H1 and H2). Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by Total and Conjugated Bilirubin at Week 52	Baseline (Day 1) and at Week 52	Hepatobiliary injury and liver function were assessed as measured by total and conjugated bilirubin. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by Albumin at Week 52	Baseline (Day 1) and at Week 52	Hepatobiliary injury and liver function were assessed as measured by albumin. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Hepatobiliary Injury and Liver Function as Measured by INR at Week 52	Baseline (Day 1) and at Week 52	Hepatobiliary injury and liver function were assessed as measured by INR. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Biomarkers of Inflammation as Measured by Fibrinogen and Haptoglobin at Week 52	Baseline (Day 1) and at Week 52	Biomarkers of inflammation were assessed as measured by fibrinogen and haptoglobin. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Key Secondary Endpoint: Percentage of Participants With Response to Treatment Based on ALP Normalization at Week 52	At Week 52	Response to treatment based on normalization of ALP at Week 52 was defined as percentage of participants with ALP =\<1.0× ULN and based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.
Key Secondary Endpoint: 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 to Week 52	Baseline (up to 14 days pre-dose) and Week 52	The PBC Worst Itch NRS is a simple, self-administered patient reported outcome (PRO) questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake).
Key Secondary Endpoint: Change From Baseline in Pruritus Based on PBC Worst Itch NRS Score in Participants With Baseline PBC Worst Itch NRS Score ≥4 to Week 24	Baseline (up to 14 days pre-dose) and Week 24	The PBC Worst Itch NRS is a simple, self-administered PRO questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake).
Percentage of Participants With Response to Treatment According to ALP < 3x ULN, Aspartate Aminotransferase (AST) < 2x ULN and TB =< 1 Milligrams Per Deciliter (mg/dL) (Paris I) at Week 52	At Week 52	Response to treatment was according to ALP \< 3x ULN, AST \< 2x ULN and TB =\< 1 mg/dL (Paris I) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.
Percentage of Participants With Response to Treatment According to ALP =< 1.5x ULN, AST =< 1.5x ULN and TB =< 1 mg/dL (Paris II) at Week 52	At Week 52	Response to treatment was according to ALP =\< 1.5x ULN, AST =\< 1.5x ULN and TB =\< 1 mg/dL (Paris II) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.
Percentage of Participants With Response to Treatment According to TB Decrease of 15% Change From Baseline at Week 52	At Week 52	Response to treatment was according to TB decrease of 15% change from baseline at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Percentage of Participants With Response to Treatment According to Normalization of TB (TB =< ULN) and/or Albumin (ALB >= Lower Limit of Normal [LLN]) (Rotterdam) at Week 52	At Week 52	Response to treatment was according to TB (TB =\< ULN) and/or albumin (ALB \>= LLN) (Rotterdam) at week 52. Participant was considered as responder at Week 52 only if total bilirubin and albumin were normal. The endpoint was analyzed in participants with abnormal total bilirubin (TB \> ULN) or albumin (ALB \< LLN) at baseline. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.
Percentage of Participants With Response to Treatment According to TB ≤0.6 x ULN at Week 52	At Week 52	Response to treatment was according to TB ≤0.6 x ULN at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.
Percentage of Participants With Response to Treatment According to ALP ≤1.67 x ULN and TB ≤1 mg/dL (Momah/ Lindor) at Week 52	At Week 52	Response to treatment was according to ALP ≤1.67 x ULN and TB ≤1 mg/dL (Momah/ Lindor) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.
Percentage of Participants With Response to Treatment According to no Worsening of TB at Week 52	At Week 52	Response to treatment was according to no worsening of TB, which was defined as level of TB \<ULN or no increase from baseline of more than 0.1 x ULN at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.
Percentage of Participants With Response to Treatment According to Complete Biochemical Response at Week 52	At Week 52	Response to treatment according to complete biochemical response which was defined as \<= ULN values of ALP, TB, AST, ALT and ALB, and international normalized ratio (INR) at Week 52. It was based on the composite strategy imputing non-response for participants who experienced ICEs (study treatment discontinuation or use of rescue therapy for PBC) prior to Week 52.
PBC 5-, 10- and 15-year Risk Scores Based on United Kingdom (UK)-PBC Score at Week 52	At Week 52	The UK-PBC risk score was defined by the mean percentage risk that a PBC participant treated with UDCA would develop liver failure requiring liver transplantation in 5, 10, and 15 years from diagnosis. It is calculated from the following equation at week 52 as follows: UK-PBC score = 0.0287854\*(alpEPxULN-1.722136304) - 0.0422873\*(\[{altastEP x ULN/10}\^-1\] - 8.675729006) + 1.4199 \* (LN(bilEPxULN /10)+2.709607778) - 1.960303\*(alb x LLN -1.17673001)-0.4161954\*(plt x LLN -1.873564875). The survival S(t) for any given participants was then calculated by S(t) = S0(t) exp(UK-PBC score). Here, alpEP x ULN=ALP /Upper Level Normal ALP at the timepoint, altastEPxULN=(ALT, AST or TA) /upper level normal of the value at the timepoint, bilEP x ULN=bilirubin /upper level normal bilirubin at the timepoint, alb x LLN=alb /alb lower level normal at baseline and plt x LLN=plt/plt lower level normal at baseline. Lower UK-PBC score predicts lower risk and better prognosis.
Change From Baseline in Biomarkers of Inflammation as Measured by High-sensitivity C-reactive Protein (hsCRP) at Week 52	Baseline (Day 1) and at Week 52	Biomarkers of inflammation were assessed as measured by hsCRP. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Biomarkers of Inflammation as Measured by Tumor Necrosis Factor Alpha at Week 52	Baseline (Day 1) and at Week 52	Biomarkers of inflammation were assessed as measured by TNF-alpha. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Immune Response as Measured by Immunoglobulin (Ig)G and IgM at Week 52	Baseline (Day 1) and at Week 52	Immune response was assessed as measured by IgG and IgM. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Cytokeratin-18 (CK-18) at Week 52	Baseline (Day 1) and at Week 52	Biomarkers and non-invasive measures of hepatic fibrosis were assessed as measured by CK-18 (M30 and M65). Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Enhanced Liver Fibrosis (ELF) and Plasminogen Activator Inhibitor-1 (PAI-1) at Week 52	Baseline (Day 1) and at Week 52	Biomarkers and non-invasive measures of hepatic fibrosis were assessed as measured by ELF: hyaluronic acid \[HA\], type 2 procollagen peptide \[PIINP\], tissue inhibitor of metalloproteinases-1\[TIMP-1\]) and PAI-1. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Biomarkers and Non-invasive Measures of Hepatic Fibrosis as Measured by Transforming Growth Factor Beta (TGF-beta) at Week 52	Baseline (Day 1) and at Week 52	Biomarkers and non-invasive measures of hepatic fibrosis were assessed as measured by TGF-beta. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Liver Stiffness Measured by Transient Elastography (TE) at Week 52	Baseline (Day 1) and at Week 52	FibroScan® TE device (Echosens, Paris, France) is a non-invasive technique used to measure liver stiffness, which correlated with fibrosis. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.
Change From Baseline in Lipid Parameters at Week 52	Baseline (Day 1) and at Week 52	Blood samples were collected at specified timepoints for assessment of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol and triglycerides (TG). Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 52	Baseline (Day 1) and at Week 52	Blood samples were collected at specified timepoints for assessment of FPG. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis at Week 52	Baseline (Day 1) and at Week 52	Blood samples were collected at specified timepoints for assessment bile acids and biomarkers of bile acid synthesis. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline at Week 52 in Bile Acids and Biomarkers of Bile Acid Synthesis as Measured by 7 Alpha-hydroxy-4-cholesten-3-one (C4) at Week 52	Baseline (Day 1) and at Week 52	Blood samples were collected at specified timepoints for assessment of bile acids and biomarkers of bile acid synthesis as measured by C4. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Bile Acids and Biomarkers of Bile Acid Synthesis as Measured Fibroblast Growth Factor 19 at Week 52	Baseline (Day 1) and at Week 52	Blood samples were collected at specified timepoints for assessment bile acids and biomarkers of bile acid synthesis as measured by Fibroblast Growth Factor 19. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Percentage of Participants With Response in PBC Worst Itch NRS Score at Weeks 24 and 52	Baseline (up to 14 days pre-dose) and at Week 24 and Week 52	The PBC Worst Itch NRS is a simple, self-administered PRO questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Response to PBC Worst Itch NRS was according to clinically meaningful change at least 30% reduction; one point, two points or three points decrease in score from baseline in participants with a baseline NRS score ≥4. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake).
Percentage of Participants With no Worsening of Pruritus as Measured by the PBC Worst Itch NRS Score at Weeks 24 and 52	Baseline (up to 14 days pre-dose) and at Week 24 and Week 54	The PBC Worst Itch NRS is a simple, self-administered PRO questionnaire that measures itch intensity. Participants rate intensity of their worst Itch on an 11-point scale ranging from 0 (no itch) to 10 (worst itch imaginable). Total score ranged from 0 (no itch) to 10 (worst itch imaginable). Higher scores indicated worse outcomes. Baseline was defined as the average of the daily PBC Worst itch scores on available data within 14 days prior the day of randomization. Post-baseline data was defined as the average of the daily PBC Worst itch scores on available data in 4-week period intervals (available data every 28 days after the day of first study drug intake). A worsening of Pruritus was defined by a positive change from baseline in PBC Worst Itch NRS score greater than 2 at week 24 and 52.
Change From Baseline in 5-D Itch at Week 52	Baseline (Day 1) and at Week 52	The 5-D Itch scale is a questionnaire that has been validated in several different diseases. It assesses symptoms in terms of 5 domains: duration: score range 1 (less than 6 hours) to 5 (all day); degree: score range 1 (not present) to 5 (unbearable); duration: score range 1 (less than 6 hours) and 5 (all day); direction: score range 1(completely resolved) and 5 (getting worse); disability: score range 1 (never affects or not applicable) and 5 (delays falling asleep and frequently wakes up at night or always affects this activity) and distribution: where the question was to mark where itching is present in body parts over the last two weeks. Participants rated their symptoms over preceding 2-week period on a 1 to 5 scale, with 5 being the most affected. The 5-D Itch total score ranged between 5 (no pruritus) and 25 (most severe pruritus). Higher scores indicated worse outcomes. Baseline= last non-missing value on or before the first dose of the randomized study medication.
Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Short Form 7a at Week 52	Baseline (Day 1) and at Week 52	The PROMIS Fatigue Short Form 7a consists of seven items that measure both the experience of fatigue and the interference of fatigue on daily activities over the past week. Participants completed the PROMIS Fatigue Short Form 7a and answered following questions on a scale from 1 (never) to 5 (always) : "How often did you feel tired"; "How often did you experience extreme exhaustion"; "How often did you run out of energy"; "How often did your fatigue limit you at work"; "How often were you too tired to think clearly"; "How often were you too tired to take a bath or shower" and 'How often did you have enough energy to exercise strenuously". T-score values include mean of 50 and standard deviation of 10. The PROMIS Fatigue T-score ranged from 29.4 (best) to 83.2 (worst). Higher scores indicated worse outcomes. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.
Change From Baseline in Epworth Sleepiness Scale (ESS) at Week 52	Baseline (Day 1) and at Week 52	The ESS is a short, self-administered questionnaire that consists of 8 questions asking to rate how likely it is to fall asleep in everyday situations (each question can be scored from 0 to 3 points; '0' indicates no chance of dozing and '3' indicates high chance of dozing). It provides a total score which has been shown to relate to the participant's level of daytime sleepiness (total score range 0 \[no sleepiness\] to 24 points \[significant sleepiness\]). The total score is the sum of all item scores and ranged from 0 (best) to 24 (worst). Higher scores indicated more chances of sleepiness. Participants were asked to complete the ESS with regard to the level of sleepiness they experienced over approximately the past 7 days. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.
Change From Baseline in PBC-40 at Week 52	Baseline (Day 1) and at Week 52	PBC-40 assess symptoms across 6 domains:symptoms,itch,fatigue,cognitive,emotional and social. Participants responded on verbal response scale,depending on section options range from 'never'/'not at all'/'strongly disagree' to 'always'/'very much'/'strongly agree'.5 items (3/3 in itch domain and 2/10 in social domain)also included a 'does not apply' option.Domains:Symptoms(7 questions)score range 7-35,Itch(3 questions)score range 3-15,Fatigue(11 questions)score range 11-55,Cognitive(6 questions)score range 6-30,Emotional(3 questions)score range 3-15,Social(10 questions)score range 10-50.Score for each domain was provided(total score was not calculated),with each verbal response scale correlating to score of 1-5 per item(0-5 on items with a 'does not apply' option);5=most affected.Individual item scores are summed to give total domain score.Higher scores=worse outcomes.PBC-40 had 4-week recall period.Baseline=last non-missing value on or before first dose of randomized study medication.
Change From Baseline in Health Utility as Measured by the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) at Week 52	Baseline (Day 1) and at Week 52	The EQ-5D-5L is a 6-item, standardized questionnaire that assesses mobility, self-care, usual activities, pain/discomfort, anxiety/depression, and overall health state. The visual analog scale (VAS) of EQ-5D-5L questionnaire is numbered from 0 (worst) to 100 (best). Higher scores indicated better outcomes. Baseline was defined as the last non-missing value on or before the first dose of the randomized study medication.
Change From Baseline in T-Scores for Bone Mineral Density Assessed by Dual-energy X-ray Absorptiometry (DEXA) Scanning at Week 52	Baseline (Day 1) and at Week 52	DEXA scanning (hip and lumbar) was performed in participants to assess bone mineral density (femoral neck, lumbar and total hip). T-scores were calculated based on actual measured bone density value. The T-score compared a participant's bone density against that of a healthy 30-year-old adult. T-scores were used to determine primary osteoporosis, which exists on its own without any other cause and were divided into 3 categories: low risk, medium risk, and high risk (osteoporosis). T-scores measure the number of minerals in a participant's bone. A participant's level of bone loss was compared to that of a typical, healthy 30-year-old adult. A score ≥-1.0 indicates low risk, medium risk is a score between-2.5 and -1.0, and a high risk/osteoporosis is a score ≤-2.5. A positive change in T-score indicates an improvement in bone mineral density. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Serum Markers of Bone Turnover Carboxy Terminal Crosslinked Telopeptides of Type 1 Collagen [CTX] at Week 52	Baseline (Day 1) and at Week 52	Blood samples were collected at specified timepoints for assessment of serum markers of bone turnover, CTX. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Change From Baseline in Serum Markers of Bone Turnover Type 1 Procollagen Peptide [P1NP]) at Week 52	Baseline (Day 1) and at Week 52	Blood samples were collected at specified timepoints for assessment of serum markers of bone turnover, P1NP. Baseline was defined as the last non-missing central value on or before the first dose of the randomized study medication.
Percentage of Participants With Onset of Clinical Outcomes	From Day 1 up to Week 52	Onset of clinical outcomes were described as a composite endpoint composed of the following: model for end stage liver disease sodium (MELD-Na) \>14 for participants with baseline MELD-Na \<12; liver transplant; uncontrolled ascites requiring treatment; hospitalization for new onset or recurrence of any including, variceal bleed, hepatic encephalopathy defined as West-Haven score of 2 or more and spontaneous bacterial peritonitis; and death.
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Treatment-emergent Serious Adverse Events (TESAEs) and Adverse Events of Special Interest (AESIs)	TEAEs were collected from the start of study treatment administration (Day 1) up to DCO date of 01 June 2023, approximately 980 days.	An AE was any untoward medical occurrence in a participant or clinical investigation participant who was administered an investigational product, and which does not necessarily have a causal relationship with treatment. A TEAE was defined as any AE with onset during TEAE assessment period, or any event started prior to first dose of treatment and worsened or became serious during the TEAE assessment period. An SAE was any AE that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital abnormality/birth defect. An AESI was an AE that might not be serious but was of special importance to a particular treatment or class.
Plasma Concentrations of Elafibranor and GFT1007	Week 4: pre-dose, 0.5 hour, 1.5 hours, between 2-3 hours, 4 hours and 6 hours post-dose	Blood samples were collected at specified timepoints to evaluate plasma concentration of Elafibranor and its metabolite GFT1007.

Trial Locations

Locations (115)

Keck Medical Center of USC; 🇺🇸 Los Angeles, California, United States

Henry Ford Health System; 🇺🇸 Novi, Michigan, United States

Tiervlei Trial Centre; 🇿🇦 Cape Town, Western Cape, South Africa

Liver Institute Northwest; 🇺🇸 Seattle, Washington, United States

Schiff Center for Liver Diseases/University of Miami; 🇺🇸 Miami, Florida, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Consultants for Clinical Research; 🇺🇸 Cincinnati, Ohio, United States

American Research Corporation; 🇺🇸 San Antonio, Texas, United States

Vanderbilt Digestive Disease Center; 🇺🇸 Nashville, Tennessee, United States

University of Utah Hospital-Division of Gastroenterology, Hepatology, and Nutrition; 🇺🇸 Salt Lake City, Utah, United States

CHU Amiens Picardie; 🇫🇷 Amiens, France

Ruane Clinical Research Group Inc.; 🇺🇸 Los Angeles, California, United States

South Denver Gastroenterology, P.C.; 🇺🇸 Englewood, Colorado, United States

California Pacific Medical Center - Sutter Pacific Medical Foundation; 🇺🇸 San Francisco, California, United States

Digestive Healthcare of Georgia; 🇺🇸 Atlanta, Georgia, United States

Texas Digestive Disease Consultants dba GI Alliance; 🇺🇸 Fort Worth, Texas, United States

The University of Texas Southwestern Medical Center-IDS Aston Pharmacy; 🇺🇸 Dallas, Texas, United States

University of Colorado Denver and Hospital; 🇺🇸 Aurora, Colorado, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Texas Clinical Research Institute, LLC; 🇺🇸 Arlington, Texas, United States

Columbia University Medical Center - Center for Liver Disease and Transplantation; 🇺🇸 New York, New York, United States

University of California, Davis Medical Center; 🇺🇸 Sacramento, California, United States

University Hospitals Cleveland Medical Center; 🇺🇸 Cleveland, Ohio, United States

NYU Langone Health / NYU Grossman School of Medicine; 🇺🇸 New York, New York, United States

Investigational Drug Service Pharmacy Penn State Milton S. Hershey Medical Center; 🇺🇸 Hershey, Pennsylvania, United States

The Ohio State University Wexner Medical Center; 🇺🇸 Columbus, Ohio, United States

The New York-Presbyterian Hospital, David H. Koch Center; 🇺🇸 New York, New York, United States

Carolinas Centre for Liver disease/ Atrium Health; 🇺🇸 Huntersville, North Carolina, United States

Hospital de Clínicas de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil

Shared Health Inc.-Operating as Health Sciences Centre-John Buhler Research Centre; 🇨🇦 Winnipeg, Manitoba, Canada

Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM); 🇨🇦 Montréal, Canada

Hôpital Henri Mondor; 🇫🇷 Créteil, France

Hôpital Haut Lévêque; 🇫🇷 Pessac, France

Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre; 🇫🇷 Strasbourg, France

Hôpital Cochin; 🇫🇷 Paris, France

Groote Schuur Hospital, University of Cape Town - Clinical Research Centre; 🇿🇦 Cape Town, Western Cap, South Africa

Hôpital Robert Debré - CHU de Reims; 🇫🇷 Reims, France

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Gastro - Sudien; 🇩🇪 Berlin, Germany

Medizinische Hochschule Hannover; 🇩🇪 Hannover, Germany

Ospedale Civile di Baggiovara-Struttura Complessa di Medicina ad indririzzo Metabolico Nutrizionale; 🇮🇹 Modena, Località Baggiovara, Italy

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Universitario Donostia; 🇪🇸 San Sebastián, Spain

Hospital Universitario Virgen del Rocio; 🇪🇸 Sevilla, Spain

Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Gastroentoloji Bilim Dali; 🇹🇷 Istanbul, Pendik, Turkey

Cambridge University Hospitals NHS Foundation Trust - Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

King's College Hospital. King's College NHS Foundation Trust; 🇬🇧 London, United Kingdom

Inselspital, Universitätsspital Bern Universitätsklinik für Viszerale chirurgie und Medizin Hepatologie; 🇨🇭 Bern, Switzerland

Frimley Health NHS Foundation Trust - Frimley Park Hospital; 🇬🇧 Camberley, United Kingdom

Fondazione Epatocentro Ticino; 🇨🇭 Lugano, Switzerland

Ege Universitesi Tip Fakultesi Hastanesi; 🇹🇷 İzmir, Bornova, Turkey

Plymouth Hospitals NHS Trust, Derriford Hospital; 🇬🇧 Plymouth, United Kingdom

The Newcastle upon Tyne Hospitals NHS Foundation Trust-Freeman Hospital; 🇬🇧 Newcastle-upon-Tyne, Newcastle, United Kingdom

Hull University Teaching Hospitals NHS Trust , Hull Royal Infirmary; 🇬🇧 Hull, United Kingdom

Nottingham University Hospitals NHS Trust - Queen's Medical Centre (QMC); 🇬🇧 Nottingham, United Kingdom

Hospital General Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Universitario Puerta de Hierro -Madrid; 🇪🇸 Madrid, Spain

Complexo Hospitalario Universitario de Pontevedra; 🇪🇸 Pontevedra, Spain

The Liver Institute at Methodist Dallas Medical Center; 🇺🇸 Dallas, Texas, United States

Liver Center of Texas, PLLC; 🇺🇸 Dallas, Texas, United States

Liver Associates of Texas, P.A.; 🇺🇸 Houston, Texas, United States

Gastro health & Nutrition-Victoria; 🇺🇸 Victoria, Texas, United States

St. Luke's Health-Baylor St Luke's Medical center - Advanced Liver Therapies Research; 🇺🇸 Houston, Texas, United States

Maryview Hospital Inc, Bon Secours Liver Institute of Hampton Roads; 🇺🇸 Newport News, Virginia, United States

Richmond Community Hospital LLC, Bon Secours Liver Institute of Richmond; 🇺🇸 Richmond, Virginia, United States

Virginia Commonwealth University Clinical Research Services Unit (CRSU); 🇺🇸 Richmond, Virginia, United States

Hospital Universitario Marqués de Valdecilla; 🇪🇸 Santander, Spain

UPMC Center for Liver Diseases; 🇺🇸 New Hyde Park, New York, United States

Saint Louis University; 🇺🇸 Saint Louis, Missouri, United States

Beth Israel Deaconess Medical Center (BIDMC); 🇺🇸 Boston, Massachusetts, United States

University of Virginia Medical Center; 🇺🇸 Charlottesville, Virginia, United States

Hospital Espanol De Mendoza; 🇦🇷 Godoy Cruz, Mendoza, Argentina

Centro de Investigaciones Clinicas (CIC); 🇨🇱 Viña Del Mar, Region De Valparaiso, Chile

Intermountain Medical Center - Transplant Services; 🇺🇸 Murray, Utah, United States

Hospital Italiano de La Plata; 🇦🇷 La Plata, Provincia De Buenos Aires, Argentina

Charite - Universitätsmedizin Berlin- CVK - Medizinische Klinik; 🇩🇪 Berlin, Germany

Azienda Ospedaliera Universitaria Policlinico P. Giaccone, UOC di Gastroenterologia-Dip.Medicina Interna e Specialistica; 🇮🇹 Palermo, Italy

Mediclinic Constantiaberg, North Suites; 🇿🇦 Cape Town, South Africa

Hacette Universitesi Hastenesi IC, Hastaliklari Anabilim Dali, Gastronenteroloji Bilim Dali, Mithapasa Cad. Hacettepe Mah.; 🇹🇷 Ankara, Turkey

Belfast Health and Social Care Trust-Royal Victoria Hospital; 🇬🇧 Belfast, United Kingdom

Clínica Universidad de los Andes; 🇨🇱 Santiago, Chile

Hospital Clínico Universidad de Chile; 🇨🇱 Santiago, Chile

Hôpital Erasme; 🇧🇪 Brussels, Belgium

Universitätsklinikum Frankfurt; 🇩🇪 Frankfurt, Germany

Azienda Ospedaliero-Universitaria di Bologna Policlinico S. Orsola-Malpighi; 🇮🇹 Bologna, Italy

Azienda Ospedaliera San Paolo, Dipartimento di Scienza della Salute, UO Medicina VI e Pathologia e Gastroenterologia; 🇮🇹 Milano, Italy

Hospital Provincial del Centenario; 🇦🇷 Rosario, Santa Fe, Argentina

Encore Borland-Groover Clinical Research; 🇺🇸 Jacksonville, Florida, United States

Hospital Británico de Buenos Aires; 🇦🇷 Caba, Buenos Aires, Argentina

Centro de Investigacion Clinica Universidad Catolica CICUC; 🇨🇱 Santiago, Chile

CHU Grenoble Alpes - Hôpital Albert Michallon; 🇫🇷 Grenoble, France

Center for Gastroenterology and Hepatology (GHZ) Kiel; 🇩🇪 Kiel, Germany

ASST Monza - Ospedale San Gerardo, Gastroenterologia; 🇮🇹 Monza, Italy

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Medical University of South Carolina- College of Medicine; 🇺🇸 Charleston, South Carolina, United States

The Institute for Liver Health; 🇺🇸 Chandler, Arizona, United States

Hôpital Pitié-Salpétrière; 🇫🇷 Paris, France

Hospital Italiano de Buenos Aires; 🇦🇷 Caba, Buenos Aires, Argentina

Hospital Alemán; 🇦🇷 Caba, Buenos Aires, Argentina

Antwerp University Hospital; 🇧🇪 Edegem, Belgium

Universitair Ziekenhuis Gent; 🇧🇪 Gent, Belgium

University Hospital Leuven; 🇧🇪 Leuven, Belgium

Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo-HCFMUSP; 🇧🇷 São Paulo, Sao Paulo, Brazil

Centre Hospitalier Régional d'Orléans; 🇫🇷 Orléans, France

EUGASTRO GmbH; 🇩🇪 Leipzig, Germany

Azienda Ospedale- Università degli Studi di Padova UOC Gastroenterologia; 🇮🇹 Padova, Italy

University of Calgary Liver Unit - Heritage Medical Research Clinic (HMRC); 🇨🇦 Calgary, Alberta, Canada

Gordon and Leslie Diamond Health Care Centre, Division of Gastroenterology; 🇨🇦 Vancouver, British Columbia, Canada

Hospital de La Serena; 🇨🇱 La Serena, Coquimbo, Chile

Hôpital Saint-Antoine; 🇫🇷 Paris, France

Universitätsmedizin der Johannes Gutenberg-Universität Mainz; 🇩🇪 Mainz, Germany

Yale School of Medicine, Digestive Diseases; 🇺🇸 New Haven, Connecticut, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Kansas Medical Center; 🇺🇸 Kansas City, Kansas, United States