Phase 2 N=45 Randomized Quadruple-blind Treatment

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

Primary Biliary Cholangitis (PBC)

Bottom Line

View on ClinicalTrials.gov: NCT03124108 ↗

Enrolled (actual)

Serious AEs

4.4%

Results posted

Sep 2019

Primary outcome: Primary: Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) Levels at Week 12 (Endpoint) — -48.264; -40.640; 3.190 Percent change — p=<0.001

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: Elafibranor 80 mg (Drug); Elafibranor 120 mg (Drug); Placebo (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Genfit
Primary completion: Oct 2018

Outcome Measures

Outcome	Result	p-value
PRIMARY Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) Levels at Week 12 (Endpoint)	-48.264; -40.640; 3.190	<0.001 sig
SECONDARY 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)	66.7; 78.6; 6.7	—
SECONDARY 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)	73.3; 42.9; 0	—
SECONDARY Percentage of Participants With Response Based on PARIS I Risk Score at Endpoint	80.0; 78.6; 53.3	—
SECONDARY Percentage of Participants With Response Based on PARIS II Risk Score at Endpoint	53.3; 50.0; 0	—
SECONDARY Percentage of Participants With Response Based on Toronto I Risk Score at Endpoint	66.7; 78.6; 6.7	—
SECONDARY Percentage of Participants With Response Based on Toronto II Risk Score at Endpoint	66.7; 78.6; 6.7	—
SECONDARY Median Percentage Risk as Assessed by United Kingdom-Primary Biliary Cholangitis (UK-PBC) Risk Total Score at Endpoint	0.80; 0.95; 1.30; 2.60; 3.05; 4.40	—
SECONDARY Percentage of Participants With Response Defined by 10, 20 and 40 Percent Reduction in Alkaline Phosphatase	93.3; 92.9; 13.3; 93.3; 92.9; 6.7	—
SECONDARY Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Endpoint	13.3; 21.4; 0	—
SECONDARY Percentage of Participants With Response Defined by Normalized Bilirubin (BIL) at Endpoint	86.7; 92.9; 93.3	—
SECONDARY Percentage of Participants With Response Defined by Normalized Albumin (ALB) Levels at Endpoint	100; 100; 100	—
SECONDARY Change From Baseline in Alanine Aminotransferase (ALT) Levels at Endpoint	-0.5; 7.3; -1.2	—
SECONDARY Change From Baseline in Aspartate Aminotransferase (AST) Levels at Endpoint	6.0; 11.1; -4.3	—
SECONDARY Change From Baseline in Gamma-glutamyl Transferase (GGT) Levels at Endpoint	-91.5; -61.9; 0.6	—
SECONDARY Change From Baseline in 5 Prime (') Nucleotidase Levels at Endpoint	-7.81; -4.59; -0.47	—
SECONDARY Change From Baseline in Total Bilirubin (BIL) Levels at Endpoint	-0.23; -0.51; -0.01	—
SECONDARY Change From Baseline in Conjugated Bilirubin Levels at Endpoint	0.34; -0.06; 0.45	—
SECONDARY Change From Baseline in Albumin Levels at Endpoint	2.2; 2.3; 0.0	—
SECONDARY Change From Baseline in Cholesterol Levels at Endpoint	-0.455; -0.387; 0.043	—
SECONDARY Change From Baseline in Low-density Lipoprotein (LDL) Cholesterol Levels at Endpoint	-0.366; -0.334; 0.061	—
SECONDARY Change From Baseline in High-density Lipoprotein (HDL) Cholesterol Levels at Endpoint	-0.017; 0.059; -0.007	—
SECONDARY Change From Baseline in Triglycerides Levels at Endpoint	-0.155; -0.253; -0.019	—
SECONDARY Change From Baseline in Total Free Bile Acid Levels at Endpoint	-248.88; -673.71; -135.20	—
SECONDARY Change From Baseline in Total Conjugated Bile Acid Levels at Endpoint	5008.99; -3280.16; 1873.22	—
SECONDARY Change From Baseline in Total Bile Acid Levels at Endpoint	4760.11; -3953.86; 1738.02	—
SECONDARY Change From Baseline in 7 Alpha-hydroxy-4-cholesten-3-one Levels at Endpoint	-16.29; -10.04; 5.22	—
SECONDARY Change From Baseline in Fibroblast Growth Factor-19 Levels at Endpoint	-21.67; -16.96; -47.08	—
SECONDARY Change From Baseline in Immunoglobulin M (IgM) Levels at Endpoint	-0.339; -0.472; -0.076	—
SECONDARY Change From Baseline in Tumor Necrosis Factor Levels at Endpoint	0.066; 0.154; 0.053	—
SECONDARY Change From Baseline in Transforming Growth Factor Beta Levels at Endpoint	734.7; 297.2; -1163.0	—
SECONDARY Change From Baseline in Interleukin 6 Levels at Endpoint	-0.021; -0.261; -0.165	—
SECONDARY Change From Baseline in Plasminogen Activator Inhibitor-1 Antigen (AG) Levels at Endpoint	-0.483; -1.739; -1.456	—
SECONDARY Change From Baseline in Cytokeratin-18 Levels at Endpoint	26.12; 163.33; 17.93; 114.31; 238.97; -53.16	—
SECONDARY Change From Baseline in Autotaxin Levels at Endpoint	4.6; 49.9; 35.1	—
SECONDARY C-reactive Protein Level at Endpoint	2.74; 2.84; 4.01	—
SECONDARY Change From Baseline in Haptoglobin Levels at Endpoint	-0.265; -0.254; 0.025	—
SECONDARY Change From Baseline in Fibrinogen Levels at Endpoint	-0.865; -0.452; -0.072	—
SECONDARY Change From Baseline in 5D-Itch Scale Total Score	-2.1; -0.1; 0.8	—
SECONDARY Change From Baseline in Pruritus as Assessed by Visual Analogue Scale (VAS) Total Score	-4.4; -4.7; 9.3	—
SECONDARY Change From Baseline in Primary Biliary Cholangitis -40 (PBC-40) Quality of Life (QoL) Questionnaire Scores	-0.3; -0.6; -0.6; 0.6; -1.3; -0.7	—
SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events	12; 13; 12; 0; 2; 0	—

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

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)

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03124108). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.