search
Back to results

Study to Evaluate the Efficacy and Safety of Elafibranor in Patients With Primary Biliary Cholangitis (PBC) and Inadequate Response to Ursodeoxycholic Acid

Primary Purpose

Primary Biliary Cholangitis (PBC)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Elafibranor 80 mg
Elafibranor 120 mg
Placebo
Sponsored by
Genfit
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Biliary Cholangitis (PBC) focused on measuring Elafibranor, Primary Biliary Cholangitis, Alkaline phosphatase

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Must have provided written informed consent

  2. Definite or probable PBC diagnosis as demonstrated by the presence of at least 2 of the following 3 diagnostic factors:

    • History of elevated ALP levels for at least 6 months prior to Day 0 (randomization visit)
    • Positive Anti-Mitochondrial Antibodies (AMA) titers (> 1/40 on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies
    • Liver biopsy consistent with PBC
  3. ALP >= 1.67x upper limit of normal (ULN)
  4. Taking UDCA for at least 12 months (stable dose for ≥ 6 months) prior to screening visit
  5. Contraception: Females participating in this study must be of non-childbearing potential or must be using highly efficient contraception for the full duration of the study and for 1 month after the end of treatment.

Exclusion Criteria:

  1. History or presence of other concomitant liver diseases
  2. Screening creatine phosphokinase (CPK) > upper limits of normal (ULN)
  3. Screening alanine transaminase (ALT) or aspartate aminotransferase (AST) > 5 ULN
  4. Screening total bilirubin > 2 ULN
  5. Screening serum creatinine > 1.5 mg/dl
  6. Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as patients with markers of kidney damage or estimated glomerular filtration rate [eGFR] of less than 60 mL/min/1.73 m^2).
  7. Patients with moderate or severe hepatic impairment (defined as Child-Pugh B/C)
  8. Platelet count <150 X 10^3/microliter
  9. Albumin <3.5 g/dL
  10. Presence of clinical complications of PBC or clinically significant hepatic decompensation
  11. If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
  12. Known history of human immunodeficiency virus (HIV) infection
  13. Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease)

Sites / Locations

  • Mayo Clinic in Arizona
  • Schiff Center for Liver Diseases
  • Cleveland Clinic Florida
  • Piedmont Research Institute
  • Massachusetts General Hospital
  • Beth Israel Deaconess Medical Center
  • Northwell Health Institution
  • Asheville Gastroenterology Associates
  • UT Southwestern Medical Center
  • Baylor College of Medicine
  • University of Virginia
  • Virginia Commonwealth University
  • Swedish Medical Center
  • Hopital Saint-Antoine
  • University Hospital Frankfurt
  • Clinic for Gastroenterology and Hepatology
  • Johannes Gutenberg University
  • Liver Unit, University of Barcelona
  • Hospital De La Sant Creu St. Pau
  • University of Birmingham Centre for Liver Research
  • Addenbrooke's Hospital
  • The Royal Liverpool University Hospital
  • King's College Hospital
  • The Newcastle Upon Tyne Hosptials NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Active Comparator

Active Comparator

Arm Label

Placebo

Elafibranor 80 mg

Elafibranor 120 mg

Arm Description

Study subjects will take two tablets per day orally before breakfast with a glass of water each morning

Study subjects will take two tablets per day orally before breakfast with a glass of water each morning

Study subjects will take two tablets per day orally before breakfast with a glass of water each morning

Outcomes

Primary Outcome Measures

Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) Levels at Week 12 (Endpoint)
Relative change from baseline is in serum ALP levels at Week 12 (endpoint) were reported. Relative change from baseline is defined as percentage (%) change from baseline to endpoint.

Secondary Outcome Measures

Percentage of Participants With Response Defined by Composite Risk Scores (ALP< 1.67 * Upper Limit of Normal [ULN] at Endpoint, Total Bilirubin [BIL] Within Normal Limits at Endpoint, and Greater Than [>] 15% ALP Reduction From Baseline to Endpoint)
Percentage of participants with response defined by Composite Risk Scores (ALP Less than [<] 1.67 * ULN at endpoint, Total BIL within normal limits at endpoint, and > 15% ALP reduction from baseline to Endpoint) was reported.
Percentage of Participants With Response Defined by Composite Risk Scores (ALP < 2 * Upper Limit of Normal at Endpoint, Total Bilirubin Within Normal Limits at Endpoint, and > 40% ALP Reduction From Baseline to Endpoint)
Percentage of participants with response defined by composite risk scores (ALP < 2 * ULN at endpoint, Total BIL within normal limits at endpoint, and > 40% ALP reduction from baseline to endpoint) was reported.
Percentage of Participants With Response Based on PARIS I Risk Score at Endpoint
Percentage of participants with response based on Paris I risk score was defined as ALP less than or equal to (<=) 3 * ULN and aspartate aminotransferase (AST) <= 2 * ULN and bilirubin within normal limits.
Percentage of Participants With Response Based on PARIS II Risk Score at Endpoint
Percentage of participants with response based on Paris II risk score was defined as ALP <= 1.5 * ULN and AST <= 1.5 * ULN and bilirubin within normal limits.
Percentage of Participants With Response Based on Toronto I Risk Score at Endpoint
Percentage of participants with response based on Toronto I risk score was defined as ALP <= 1.67 *ULN.
Percentage of Participants With Response Based on Toronto II Risk Score at Endpoint
Percentage of participants with response based on Toronto II risk scores was defined as ALP <= 1.75 * ULN.
Median Percentage Risk as Assessed by United Kingdom-Primary Biliary Cholangitis (UK-PBC) Risk Total Score at Endpoint
UK-PBC risk score at endpoint estimated that the median percentage risk that a participant treated with ursodeoxycholic acid (UDCA) will develop liver failure requiring liver transplant in 5, 10 and 15 years. UK-PBC score was calculated at each of the 3 survivor functions 1-baseline survival function^exp(0.0287854*[alpEPxuln-1.722136304] - 0.0422873*[{(altastEPxuln/10)^-1} - 8.675729006] + 1.4199 * [ln{bilEPxuln /10}+2.709607778] -1.960303*[albxlln -1.17673001]-0.4161954*[ pltxlln -1.873564875]). Where: Baseline survivor function=0. 982 (at 5 years); 0. 941 (at 10 years); 0.893 (at 15 years). alpEPxuln = ALP at endpoint/upper level normal ALP; altastEPxuln=(ALT, AST) at endpoint/upper level normal of the value; bilEPxuln=bilirubin at endpoint/upper level normal bilirubin; albxlln=albumin at baseline/albumin lower level normal; pltxlln=platelet count at baseline/ platelet count lower level normal.
Percentage of Participants With Response Defined by 10, 20 and 40 Percent Reduction in Alkaline Phosphatase
Percentage of participants with response (defined by at least 10%, 20%, and 40% decrease in ALP from baseline to Endpoint) reported.
Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Endpoint
The response was defined by normalized ALP levels (ALP ULN 105 units per liter [U/L] for females, 129 U/L for males) at endpoint.
Percentage of Participants With Response Defined by Normalized Bilirubin (BIL) at Endpoint
The response was defined by normalized BIL levels (BIL ULN <1.20 milligram per deciliter [mg/dL]) at endpoint.
Percentage of Participants With Response Defined by Normalized Albumin (ALB) Levels at Endpoint
The response was defined by normalized ALB levels (3.5-5.2 gram per deciliter [g/dL] for ages 18-60 years; 3.2-4.6 g/dL for ages 61-91 years) at endpoint.
Change From Baseline in Alanine Aminotransferase (ALT) Levels at Endpoint
Change from baseline in ALT levels at endpoint was reported.
Change From Baseline in Aspartate Aminotransferase (AST) Levels at Endpoint
Change from baseline in AST levels at endpoint was reported.
Change From Baseline in Gamma-glutamyl Transferase (GGT) Levels at Endpoint
Change from baseline in GGT levels at endpoint was reported.
Change From Baseline in 5 Prime (') Nucleotidase Levels at Endpoint
Change from baseline in 5' nucleotidase levels at endpoint was reported. 5' nucleotidase is an enzyme used as a biomarker of hepatobiliary cholestasis and is less sensitive but more specific than GGT and ALP.
Change From Baseline in Total Bilirubin (BIL) Levels at Endpoint
Change from baseline in total BIL levels at endpoint was reported.
Change From Baseline in Conjugated Bilirubin Levels at Endpoint
Change from baseline in conjugated bilirubin levels at endpoint was reported.
Change From Baseline in Albumin Levels at Endpoint
Change from baseline in albumin levels at endpoint was reported.
Change From Baseline in Cholesterol Levels at Endpoint
Change from baseline in cholesterol levels at endpoints was reported.
Change From Baseline in Low-density Lipoprotein (LDL) Cholesterol Levels at Endpoint
Change from baseline in LDL-cholesterol at endpoint was reported.
Change From Baseline in High-density Lipoprotein (HDL) Cholesterol Levels at Endpoint
Change from baseline in HDL-cholesterol levels at endpoint was reported.
Change From Baseline in Triglycerides Levels at Endpoint
Change from baseline in triglycerides levels at endpoint was reported.
Change From Baseline in Total Free Bile Acid Levels at Endpoint
Change from baseline in total free bile acid levels at endpoint was reported.
Change From Baseline in Total Conjugated Bile Acid Levels at Endpoint
Change from baseline in total conjugated bile acid levels at endpoint was reported.
Change From Baseline in Total Bile Acid Levels at Endpoint
Change from baseline in total bile acid levels at endpoint was reported.
Change From Baseline in 7 Alpha-hydroxy-4-cholesten-3-one Levels at Endpoint
Change from baseline in 7 alpha-hydroxy-4-cholesten-3-one levels at endpoint was reported.
Change From Baseline in Fibroblast Growth Factor-19 Levels at Endpoint
Change from baseline in fibroblast growth factor-19 levels at endpoint was reported.
Change From Baseline in Immunoglobulin M (IgM) Levels at Endpoint
Change from baseline in IgM levels at endpoint was reported.
Change From Baseline in Tumor Necrosis Factor Levels at Endpoint
Change from baseline in tumor necrosis factor levels at endpoint was reported.
Change From Baseline in Transforming Growth Factor Beta Levels at Endpoint
Change from baseline in transforming growth factor beta levels at endpoint was reported,
Change From Baseline in Interleukin 6 Levels at Endpoint
Change from baseline in interleukin 6 levels at endpoint was reported.
Change From Baseline in Plasminogen Activator Inhibitor-1 Antigen (AG) Levels at Endpoint
Change from baseline in plasminogen activator inhibitor-1 AG levels at endpoint was reported.
Change From Baseline in Cytokeratin-18 Levels at Endpoint
Change from baseline in cytokeratin-18 (M30 and M65) levels at endpoint was reported.
Change From Baseline in Autotaxin Levels at Endpoint
Change from baseline in autotaxin levels at endpoint was reported.
C-reactive Protein Level at Endpoint
C-reactive protein level at endpoint was reported.
Change From Baseline in Haptoglobin Levels at Endpoint
Change from baseline in haptoglobin levels at endpoint was reported.
Change From Baseline in Fibrinogen Levels at Endpoint
Change from baseline in fibrinogen levels at endpoint was reported.
Change From Baseline in 5D-Itch Scale Total Score
5 dimensional (5D)-Itch Scale is a reliable, multidimensional measure of itching that has been validated in participants with chronic pruritus to detect changes over time. It consists of 5 domains: duration, degree, direction, disability, and distribution. The duration, degree and direction domains each include one item, while the disability domain has four items (sleep, leisure/social, housework/errands, work/school). All items of the first four domains were measured on a 5-point Likert scale. The distribution domain included 16 potential locations of itch, including 15 body part items (head/scalp, soles, face, palms, chest, abdomen, back, buttocks, thighs, lower legs, tops of feet/toes, tops of hands/fingers, upper arms, groin, forearms) and one point of contact with clothing or bandages. Scores of each of five domains are achieved separately and then summed together to obtain a total 5-D score. 5-D scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus).
Change From Baseline in Pruritus as Assessed by Visual Analogue Scale (VAS) Total Score
The VAS is a reliable and validated method of pruritus assessment. The VAS is adequate in assessing the severity of the symptom; it does not take into account other aspects of pruritus, such as the relative impact of pruritus on quality of life. The VAS, for pruritus assessment, requires the participant to use abstract thought processes to convert their itch severity to a mark on a continuum. A participant draws a line anywhere on the scale ranging from 0 to 10 (where 0 represents 'no itching' and 10 represents 'worst possible itching') that best represents the severity of participant's itching and the scoring involves manual measuring of the mark with a ruler on range of 0 to 100 millimeter (mm). Higher scores indicate worse itching.
Change From Baseline in Primary Biliary Cholangitis -40 (PBC-40) Quality of Life (QoL) Questionnaire Scores
PBC-40 QoL Questionnaire is a patient-derived, disease-specific QoL measure developed and validated for use in PBC. It consists of 9 domains with total 40 questions as: 1) digestion and diet (questions 1-3, total score range: 3-15); 2) experiences (questions 4-7, total score range: 4-20); 3) itching (questions 8-10, total score range: 3-15); 4) fatigue (questions 11-18, total score range: 8-40); 5) effort and planning (questions 19-21, total score range: 3-15); 6) memory and concentration (questions 22-27, total score range: 6-30); 7) affects you as a person (questions 28-33, total score range: 6-30); 8) affects your social life (questions 34-37, total score range: 4-20); 9) overall impact on your life (questions 38-40, total score range: 3-15). PBC-40 QoL Questionnaire has 40 questions, each scored on scale of 1-5 (1 = least impact, 5 = greatest impact). For each domain, scoring involved summing individual question response scores. Higher scores indicate poorer quality of life.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical (investigational) product and which does not necessarily have to have a causal relationship with this treatment. A Serious adverse event (SAE) is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization/prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is another medically important condition. TEAEs is defined as (1) it is not present when active phase of study (time of first dose) begins and is not a chronic condition that is part of patient's medical history, or it is present at start of active phase or as part of patient's medical history, but severity/frequency increases during active phase.

Full Information

First Posted
March 28, 2017
Last Updated
September 20, 2019
Sponsor
Genfit
search

1. Study Identification

Unique Protocol Identification Number
NCT03124108
Brief Title
Study to Evaluate the Efficacy and Safety of Elafibranor in Patients With Primary Biliary Cholangitis (PBC) and Inadequate Response to Ursodeoxycholic Acid
Official Title
A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study to Evaluate the Efficacy and Safety of Elafibranor at Doses of 80 mg and 120mg After 12 Weeks of Treatment in Patients With Primary Biliary Cholangitis and Inadequate Response to Ursodeoxycholic Acid
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
April 5, 2017 (Actual)
Primary Completion Date
October 31, 2018 (Actual)
Study Completion Date
October 31, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genfit

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of the study is to compare the effect of daily oral administration of elafibranor 80mg and 120 mg on change in serum alkaline phosphatase (ALP) to that of placebo in patients with PBC and inadequate response to Ursodeoxycholic acid (UDCA).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Biliary Cholangitis (PBC)
Keywords
Elafibranor, Primary Biliary Cholangitis, Alkaline phosphatase

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
45 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Study subjects will take two tablets per day orally before breakfast with a glass of water each morning
Arm Title
Elafibranor 80 mg
Arm Type
Active Comparator
Arm Description
Study subjects will take two tablets per day orally before breakfast with a glass of water each morning
Arm Title
Elafibranor 120 mg
Arm Type
Active Comparator
Arm Description
Study subjects will take two tablets per day orally before breakfast with a glass of water each morning
Intervention Type
Drug
Intervention Name(s)
Elafibranor 80 mg
Other Intervention Name(s)
GFT505
Intervention Description
Two coated tablets daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Elafibranor 120 mg
Other Intervention Name(s)
GFT505
Intervention Description
Two coated tablets daily for 12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Two coated tablets daily for 12 weeks
Primary Outcome Measure Information:
Title
Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) Levels at Week 12 (Endpoint)
Description
Relative change from baseline is in serum ALP levels at Week 12 (endpoint) were reported. Relative change from baseline is defined as percentage (%) change from baseline to endpoint.
Time Frame
Baseline, Week 12 (Endpoint)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Response Defined by Composite Risk Scores (ALP< 1.67 * Upper Limit of Normal [ULN] at Endpoint, Total Bilirubin [BIL] Within Normal Limits at Endpoint, and Greater Than [>] 15% ALP Reduction From Baseline to Endpoint)
Description
Percentage of participants with response defined by Composite Risk Scores (ALP Less than [<] 1.67 * ULN at endpoint, Total BIL within normal limits at endpoint, and > 15% ALP reduction from baseline to Endpoint) was reported.
Time Frame
Up to Week 12 (Endpoint)
Title
Percentage of Participants With Response Defined by Composite Risk Scores (ALP < 2 * Upper Limit of Normal at Endpoint, Total Bilirubin Within Normal Limits at Endpoint, and > 40% ALP Reduction From Baseline to Endpoint)
Description
Percentage of participants with response defined by composite risk scores (ALP < 2 * ULN at endpoint, Total BIL within normal limits at endpoint, and > 40% ALP reduction from baseline to endpoint) was reported.
Time Frame
Up to Week 12 (Endpoint)
Title
Percentage of Participants With Response Based on PARIS I Risk Score at Endpoint
Description
Percentage of participants with response based on Paris I risk score was defined as ALP less than or equal to (<=) 3 * ULN and aspartate aminotransferase (AST) <= 2 * ULN and bilirubin within normal limits.
Time Frame
At Week 12 (Endpoint)
Title
Percentage of Participants With Response Based on PARIS II Risk Score at Endpoint
Description
Percentage of participants with response based on Paris II risk score was defined as ALP <= 1.5 * ULN and AST <= 1.5 * ULN and bilirubin within normal limits.
Time Frame
At Week 12 (Endpoint)
Title
Percentage of Participants With Response Based on Toronto I Risk Score at Endpoint
Description
Percentage of participants with response based on Toronto I risk score was defined as ALP <= 1.67 *ULN.
Time Frame
At Week 12 (Endpoint)
Title
Percentage of Participants With Response Based on Toronto II Risk Score at Endpoint
Description
Percentage of participants with response based on Toronto II risk scores was defined as ALP <= 1.75 * ULN.
Time Frame
At Week 12 (Endpoint)
Title
Median Percentage Risk as Assessed by United Kingdom-Primary Biliary Cholangitis (UK-PBC) Risk Total Score at Endpoint
Description
UK-PBC risk score at endpoint estimated that the median percentage risk that a participant treated with ursodeoxycholic acid (UDCA) will develop liver failure requiring liver transplant in 5, 10 and 15 years. UK-PBC score was calculated at each of the 3 survivor functions 1-baseline survival function^exp(0.0287854*[alpEPxuln-1.722136304] - 0.0422873*[{(altastEPxuln/10)^-1} - 8.675729006] + 1.4199 * [ln{bilEPxuln /10}+2.709607778] -1.960303*[albxlln -1.17673001]-0.4161954*[ pltxlln -1.873564875]). Where: Baseline survivor function=0. 982 (at 5 years); 0. 941 (at 10 years); 0.893 (at 15 years). alpEPxuln = ALP at endpoint/upper level normal ALP; altastEPxuln=(ALT, AST) at endpoint/upper level normal of the value; bilEPxuln=bilirubin at endpoint/upper level normal bilirubin; albxlln=albumin at baseline/albumin lower level normal; pltxlln=platelet count at baseline/ platelet count lower level normal.
Time Frame
At Week 12 (Endpoint)
Title
Percentage of Participants With Response Defined by 10, 20 and 40 Percent Reduction in Alkaline Phosphatase
Description
Percentage of participants with response (defined by at least 10%, 20%, and 40% decrease in ALP from baseline to Endpoint) reported.
Time Frame
At Week 12 (Endpoint)
Title
Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Endpoint
Description
The response was defined by normalized ALP levels (ALP ULN 105 units per liter [U/L] for females, 129 U/L for males) at endpoint.
Time Frame
At Week 12 (Endpoint)
Title
Percentage of Participants With Response Defined by Normalized Bilirubin (BIL) at Endpoint
Description
The response was defined by normalized BIL levels (BIL ULN <1.20 milligram per deciliter [mg/dL]) at endpoint.
Time Frame
At Week 12 (Endpoint)
Title
Percentage of Participants With Response Defined by Normalized Albumin (ALB) Levels at Endpoint
Description
The response was defined by normalized ALB levels (3.5-5.2 gram per deciliter [g/dL] for ages 18-60 years; 3.2-4.6 g/dL for ages 61-91 years) at endpoint.
Time Frame
At Week 12 (Endpoint)
Title
Change From Baseline in Alanine Aminotransferase (ALT) Levels at Endpoint
Description
Change from baseline in ALT levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Aspartate Aminotransferase (AST) Levels at Endpoint
Description
Change from baseline in AST levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Gamma-glutamyl Transferase (GGT) Levels at Endpoint
Description
Change from baseline in GGT levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in 5 Prime (') Nucleotidase Levels at Endpoint
Description
Change from baseline in 5' nucleotidase levels at endpoint was reported. 5' nucleotidase is an enzyme used as a biomarker of hepatobiliary cholestasis and is less sensitive but more specific than GGT and ALP.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Total Bilirubin (BIL) Levels at Endpoint
Description
Change from baseline in total BIL levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Conjugated Bilirubin Levels at Endpoint
Description
Change from baseline in conjugated bilirubin levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Albumin Levels at Endpoint
Description
Change from baseline in albumin levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Cholesterol Levels at Endpoint
Description
Change from baseline in cholesterol levels at endpoints was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Low-density Lipoprotein (LDL) Cholesterol Levels at Endpoint
Description
Change from baseline in LDL-cholesterol at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in High-density Lipoprotein (HDL) Cholesterol Levels at Endpoint
Description
Change from baseline in HDL-cholesterol levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Triglycerides Levels at Endpoint
Description
Change from baseline in triglycerides levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Total Free Bile Acid Levels at Endpoint
Description
Change from baseline in total free bile acid levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Total Conjugated Bile Acid Levels at Endpoint
Description
Change from baseline in total conjugated bile acid levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Total Bile Acid Levels at Endpoint
Description
Change from baseline in total bile acid levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in 7 Alpha-hydroxy-4-cholesten-3-one Levels at Endpoint
Description
Change from baseline in 7 alpha-hydroxy-4-cholesten-3-one levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Fibroblast Growth Factor-19 Levels at Endpoint
Description
Change from baseline in fibroblast growth factor-19 levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Immunoglobulin M (IgM) Levels at Endpoint
Description
Change from baseline in IgM levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Tumor Necrosis Factor Levels at Endpoint
Description
Change from baseline in tumor necrosis factor levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Transforming Growth Factor Beta Levels at Endpoint
Description
Change from baseline in transforming growth factor beta levels at endpoint was reported,
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Interleukin 6 Levels at Endpoint
Description
Change from baseline in interleukin 6 levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Plasminogen Activator Inhibitor-1 Antigen (AG) Levels at Endpoint
Description
Change from baseline in plasminogen activator inhibitor-1 AG levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Cytokeratin-18 Levels at Endpoint
Description
Change from baseline in cytokeratin-18 (M30 and M65) levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Autotaxin Levels at Endpoint
Description
Change from baseline in autotaxin levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
C-reactive Protein Level at Endpoint
Description
C-reactive protein level at endpoint was reported.
Time Frame
Week 12 (Endpoint)
Title
Change From Baseline in Haptoglobin Levels at Endpoint
Description
Change from baseline in haptoglobin levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Fibrinogen Levels at Endpoint
Description
Change from baseline in fibrinogen levels at endpoint was reported.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in 5D-Itch Scale Total Score
Description
5 dimensional (5D)-Itch Scale is a reliable, multidimensional measure of itching that has been validated in participants with chronic pruritus to detect changes over time. It consists of 5 domains: duration, degree, direction, disability, and distribution. The duration, degree and direction domains each include one item, while the disability domain has four items (sleep, leisure/social, housework/errands, work/school). All items of the first four domains were measured on a 5-point Likert scale. The distribution domain included 16 potential locations of itch, including 15 body part items (head/scalp, soles, face, palms, chest, abdomen, back, buttocks, thighs, lower legs, tops of feet/toes, tops of hands/fingers, upper arms, groin, forearms) and one point of contact with clothing or bandages. Scores of each of five domains are achieved separately and then summed together to obtain a total 5-D score. 5-D scores can potentially range between 5 (no pruritus) and 25 (most severe pruritus).
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Pruritus as Assessed by Visual Analogue Scale (VAS) Total Score
Description
The VAS is a reliable and validated method of pruritus assessment. The VAS is adequate in assessing the severity of the symptom; it does not take into account other aspects of pruritus, such as the relative impact of pruritus on quality of life. The VAS, for pruritus assessment, requires the participant to use abstract thought processes to convert their itch severity to a mark on a continuum. A participant draws a line anywhere on the scale ranging from 0 to 10 (where 0 represents 'no itching' and 10 represents 'worst possible itching') that best represents the severity of participant's itching and the scoring involves manual measuring of the mark with a ruler on range of 0 to 100 millimeter (mm). Higher scores indicate worse itching.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Change From Baseline in Primary Biliary Cholangitis -40 (PBC-40) Quality of Life (QoL) Questionnaire Scores
Description
PBC-40 QoL Questionnaire is a patient-derived, disease-specific QoL measure developed and validated for use in PBC. It consists of 9 domains with total 40 questions as: 1) digestion and diet (questions 1-3, total score range: 3-15); 2) experiences (questions 4-7, total score range: 4-20); 3) itching (questions 8-10, total score range: 3-15); 4) fatigue (questions 11-18, total score range: 8-40); 5) effort and planning (questions 19-21, total score range: 3-15); 6) memory and concentration (questions 22-27, total score range: 6-30); 7) affects you as a person (questions 28-33, total score range: 6-30); 8) affects your social life (questions 34-37, total score range: 4-20); 9) overall impact on your life (questions 38-40, total score range: 3-15). PBC-40 QoL Questionnaire has 40 questions, each scored on scale of 1-5 (1 = least impact, 5 = greatest impact). For each domain, scoring involved summing individual question response scores. Higher scores indicate poorer quality of life.
Time Frame
Baseline, Week 12 (Endpoint)
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events
Description
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical (investigational) product and which does not necessarily have to have a causal relationship with this treatment. A Serious adverse event (SAE) is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization/prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is another medically important condition. TEAEs is defined as (1) it is not present when active phase of study (time of first dose) begins and is not a chronic condition that is part of patient's medical history, or it is present at start of active phase or as part of patient's medical history, but severity/frequency increases during active phase.
Time Frame
Up to Week 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Must have provided written informed consent Definite or probable PBC diagnosis as demonstrated by the presence of at least 2 of the following 3 diagnostic factors: History of elevated ALP levels for at least 6 months prior to Day 0 (randomization visit) Positive Anti-Mitochondrial Antibodies (AMA) titers (> 1/40 on immunofluorescence or M2 positive by enzyme-linked immunosorbent assay (ELISA) or positive PBC-specific antinuclear antibodies Liver biopsy consistent with PBC ALP >= 1.67x upper limit of normal (ULN) Taking UDCA for at least 12 months (stable dose for ≥ 6 months) prior to screening visit Contraception: Females participating in this study must be of non-childbearing potential or must be using highly efficient contraception for the full duration of the study and for 1 month after the end of treatment. Exclusion Criteria: History or presence of other concomitant liver diseases Screening creatine phosphokinase (CPK) > upper limits of normal (ULN) Screening alanine transaminase (ALT) or aspartate aminotransferase (AST) > 5 ULN Screening total bilirubin > 2 ULN Screening serum creatinine > 1.5 mg/dl Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as patients with markers of kidney damage or estimated glomerular filtration rate [eGFR] of less than 60 mL/min/1.73 m^2). Patients with moderate or severe hepatic impairment (defined as Child-Pugh B/C) Platelet count <150 X 10^3/microliter Albumin <3.5 g/dL Presence of clinical complications of PBC or clinically significant hepatic decompensation If female: known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating Known history of human immunodeficiency virus (HIV) infection Medical conditions that may cause non-hepatic increases in ALP (e.g., Paget's disease)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Head
Organizational Affiliation
Genfit
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic in Arizona
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Schiff Center for Liver Diseases
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Cleveland Clinic Florida
City
Weston
State/Province
Florida
ZIP/Postal Code
33331
Country
United States
Facility Name
Piedmont Research Institute
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30309
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Northwell Health Institution
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Facility Name
Asheville Gastroenterology Associates
City
Asheville
State/Province
North Carolina
ZIP/Postal Code
28801
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
Swedish Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98122
Country
United States
Facility Name
Hopital Saint-Antoine
City
Paris
ZIP/Postal Code
75012
Country
France
Facility Name
University Hospital Frankfurt
City
Frankfurt
ZIP/Postal Code
60590
Country
Germany
Facility Name
Clinic for Gastroenterology and Hepatology
City
Koln
ZIP/Postal Code
50937
Country
Germany
Facility Name
Johannes Gutenberg University
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Liver Unit, University of Barcelona
City
Barcelona
ZIP/Postal Code
08036
Country
Spain
Facility Name
Hospital De La Sant Creu St. Pau
City
Barcelona
ZIP/Postal Code
08041
Country
Spain
Facility Name
University of Birmingham Centre for Liver Research
City
Birmingham
ZIP/Postal Code
B15 2TT
Country
United Kingdom
Facility Name
Addenbrooke's Hospital
City
Cambridge
ZIP/Postal Code
CB2 0QQ
Country
United Kingdom
Facility Name
The Royal Liverpool University Hospital
City
Liverpool
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
King's College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
The Newcastle Upon Tyne Hosptials NHS Foundation Trust
City
Newcastle upon Tyne
ZIP/Postal Code
NE7 7DN
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
33484775
Citation
Schattenberg JM, Pares A, Kowdley KV, Heneghan MA, Caldwell S, Pratt D, Bonder A, Hirschfield GM, Levy C, Vierling J, Jones D, Tailleux A, Staels B, Megnien S, Hanf R, Magrez D, Birman P, Luketic V. A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA. J Hepatol. 2021 Jun;74(6):1344-1354. doi: 10.1016/j.jhep.2021.01.013. Epub 2021 Jan 21.
Results Reference
derived

Learn more about this trial

Study to Evaluate the Efficacy and Safety of Elafibranor in Patients With Primary Biliary Cholangitis (PBC) and Inadequate Response to Ursodeoxycholic Acid

We'll reach out to this number within 24 hrs