Clinical trial NCT03124108: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Primary Biliary Cholangitis (PBC)
Keywords: Elafibranor
Primary Biliary Cholangitis
Alkaline phosphatase
Lead sponsor: Genfit
Sponsor class: INDUSTRY
First posted: 2017-04-21
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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)

Primary outcomes:
measure: Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) Levels at Week 12 (Endpoint)
timeFrame: Baseline, Week 12 (Endpoint)
Secondary outcomes:
measure: 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)
timeFrame: Up to Week 12 (Endpoint)
measure: 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)
timeFrame: Up to Week 12 (Endpoint)
measure: Percentage of Participants With Response Based on PARIS I Risk Score at Endpoint
timeFrame: At Week 12 (Endpoint)
measure: Percentage of Participants With Response Based on PARIS II Risk Score at Endpoint
timeFrame: At Week 12 (Endpoint)
measure: Percentage of Participants With Response Based on Toronto I Risk Score at Endpoint
timeFrame: At Week 12 (Endpoint)
measure: Percentage of Participants With Response Based on Toronto II Risk Score at Endpoint
timeFrame: At Week 12 (Endpoint)
measure: Median Percentage Risk as Assessed by United Kingdom-Primary Biliary Cholangitis (UK-PBC) Risk Total Score at Endpoint
timeFrame: At Week 12 (Endpoint)
measure: Percentage of Participants With Response Defined by 10, 20 and 40 Percent Reduction in Alkaline Phosphatase
timeFrame: At Week 12 (Endpoint)
measure: Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Endpoint
timeFrame: At Week 12 (Endpoint)
measure: Percentage of Participants With Response Defined by Normalized Bilirubin (BIL) at Endpoint
timeFrame: At Week 12 (Endpoint)
measure: Percentage of Participants With Response Defined by Normalized Albumin (ALB) Levels at Endpoint
timeFrame: At Week 12 (Endpoint)
measure: Change From Baseline in Alanine Aminotransferase (ALT) Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Aspartate Aminotransferase (AST) Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Gamma-glutamyl Transferase (GGT) Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in 5 Prime (') Nucleotidase Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Total Bilirubin (BIL) Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Conjugated Bilirubin Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Albumin Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Cholesterol Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Low-density Lipoprotein (LDL) Cholesterol Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in High-density Lipoprotein (HDL) Cholesterol Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Triglycerides Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Total Free Bile Acid Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Total Conjugated Bile Acid Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Total Bile Acid Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in 7 Alpha-hydroxy-4-cholesten-3-one Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Fibroblast Growth Factor-19 Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Immunoglobulin M (IgM) Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Tumor Necrosis Factor Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Transforming Growth Factor Beta Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Interleukin 6 Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Plasminogen Activator Inhibitor-1 Antigen (AG) Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Cytokeratin-18 Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Autotaxin Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: C-reactive Protein Level at Endpoint
timeFrame: Week 12 (Endpoint)
measure: Change From Baseline in Haptoglobin Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Fibrinogen Levels at Endpoint
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in 5D-Itch Scale Total Score
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Pruritus as Assessed by Visual Analogue Scale (VAS) Total Score
timeFrame: Baseline, Week 12 (Endpoint)
measure: Change From Baseline in Primary Biliary Cholangitis -40 (PBC-40) Quality of Life (QoL) Questionnaire Scores
timeFrame: Baseline, Week 12 (Endpoint)
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events
timeFrame: Up to Week 12
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic in Arizona
state: Arizona
city: Miami
country: United States
facility: Schiff Center for Liver Diseases
state: Florida
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: Atlanta
country: United States
facility: Piedmont Research Institute
state: Georgia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Manhasset
country: United States
facility: Northwell Health Institution
state: New York
city: Asheville
country: United States
facility: Asheville Gastroenterology Associates
state: North Carolina
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Paris
country: France
facility: Hopital Saint-Antoine
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
city: Koln
country: Germany
facility: Clinic for Gastroenterology and Hepatology
city: Mainz
country: Germany
facility: Johannes Gutenberg University
city: Barcelona
country: Spain
facility: Liver Unit, University of Barcelona
city: Barcelona
country: Spain
facility: Hospital De La Sant Creu St. Pau
city: Birmingham
country: United Kingdom
facility: University of Birmingham Centre for Liver Research
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
city: Liverpool
country: United Kingdom
facility: The Royal Liverpool University Hospital
city: London
country: United Kingdom
facility: King's College Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hosptials NHS Foundation Trust
Study officials:
affiliation: Genfit
name: Clinical Head
role: STUDY_DIRECTOR
References:
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.