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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03124108
• Date of registration: 28/03/2017
• Prospective Registration: Yes
• Primary sponsor: Genfit
• Public title: Study to Evaluate the Efficacy and Safety of Elafibranor in Patients With Primary Biliary Cholangitis (PBC) and Inadequate Response to Ursodeoxycholic Acid
• Scientific 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
• Date of first enrolment: April 5, 2017
• Target sample size: 45
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03124108
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor).
• Phase: Phase 2

Countries of recruitment

France, Germany, Spain, United Kingdom, United States

Contacts

• Name: Clinical Head
• Affiliation: Genfit

Key inclusion & exclusion 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)



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Primary Biliary Cholangitis (PBC)

Intervention(s)

Drug: Elafibranor 120 mg

Drug: Placebo

Drug: Elafibranor 80 mg

Primary Outcome(s)

Relative Change From Baseline in Serum Alkaline Phosphatase (ALP) Levels at Week 12 (Endpoint) [Time Frame: Baseline, Week 12 (Endpoint)]

Secondary Outcome(s)

Change From Baseline in 5 Prime (') Nucleotidase Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Total Bile Acid Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Gamma-glutamyl Transferase (GGT) Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Percentage of Participants With Response Based on PARIS II Risk Score at Endpoint [Time Frame: At Week 12 (Endpoint)]

Change From Baseline in 5D-Itch Scale Total Score [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Autotaxin Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Cytokeratin-18 Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Fibroblast Growth Factor-19 Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Albumin Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in High-density Lipoprotein (HDL) Cholesterol Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Haptoglobin Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Percentage of Participants With Response Defined by 10, 20 and 40 Percent Reduction in Alkaline Phosphatase [Time Frame: At Week 12 (Endpoint)]

C-reactive Protein Level at Endpoint [Time Frame: Week 12 (Endpoint)]

Change From Baseline in Alanine Aminotransferase (ALT) Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Interleukin 6 Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Low-density Lipoprotein (LDL) Cholesterol Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

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) [Time Frame: Up to Week 12 (Endpoint)]

Change From Baseline in Plasminogen Activator Inhibitor-1 Antigen (AG) Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Conjugated Bilirubin Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Pruritus as Assessed by Visual Analogue Scale (VAS) Total Score [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Primary Biliary Cholangitis -40 (PBC-40) Quality of Life (QoL) Questionnaire Scores [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Total Free Bile Acid Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Tumor Necrosis Factor Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Total Conjugated Bile Acid Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Transforming Growth Factor Beta Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Cholesterol Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Median Percentage Risk as Assessed by United Kingdom-Primary Biliary Cholangitis (UK-PBC) Risk Total Score at Endpoint [Time Frame: At Week 12 (Endpoint)]

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Treatment Emergent Adverse Events [Time Frame: Up to Week 12]

Change From Baseline in 7 Alpha-hydroxy-4-cholesten-3-one Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Aspartate Aminotransferase (AST) Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Immunoglobulin M (IgM) Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Total Bilirubin (BIL) Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Change From Baseline in Triglycerides Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Percentage of Participants With Response Based on PARIS I Risk Score at Endpoint [Time Frame: At Week 12 (Endpoint)]

Percentage of Participants With Response Defined by Normalized Albumin (ALB) Levels at Endpoint [Time Frame: At Week 12 (Endpoint)]

Change From Baseline in Fibrinogen Levels at Endpoint [Time Frame: Baseline, Week 12 (Endpoint)]

Percentage of Participants With Response Based on Toronto I Risk Score at Endpoint [Time Frame: At Week 12 (Endpoint)]

Percentage of Participants With Response Based on Toronto II Risk Score at Endpoint [Time Frame: At Week 12 (Endpoint)]

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) [Time Frame: Up to Week 12 (Endpoint)]

Percentage of Participants With Response Defined by Normalized Alkaline Phosphatase Levels at Endpoint [Time Frame: At Week 12 (Endpoint)]

Percentage of Participants With Response Defined by Normalized Bilirubin (BIL) at Endpoint [Time Frame: At Week 12 (Endpoint)]

Secondary ID(s)

2016-003817-80

GFT505B-216-1

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 24/09/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03124108